THE WELCH COMPANY
440 Davis Court #1602
San Francisco, CA 94111-2496
415 781 5700
rod@welchco.com


S U M M A R Y


DIARY: November 25, 2013 00:05 AM Monday; Rod Welch

VA confirm understandings meetings at SF Medical Center on treating arterialsclorosis.

1...Summary/Objective
2...Hyperlipidemia Not Controlled Cholesterol Elevated Despite Exercise
3...Cholesterol Elevated Despite Exercise Discuss Clinical Trial
4...Clinical Trial Considered Lower Cholesterol Without Statin Drugs
5...Lipid Lab LDL HDL TG Conflicts Hiking Weight Loss
6...Lab Lipid LDL HDL TG Conflicts Hiking Weight Loss
7...Cholesterol Elevated Despite Exercise Weight Loss
8...Hyperlipidemia Not Controlled Cholesterol Elevated Despite Exercise
9...Wicked Problems Good Condition Hiking Weight Loss Masks Poor Health
10...Good Condition False Positive Hiking Weight Loss Masks Poor Health
11...Hiking Good Condition Masks Poor Health CVD with High LDL-P
12...False Positive Patient Good Condition Hiking Masks Rising CVD
13...Atorvastatin Prescribed with Ezetimibe Increase HDL Lower Triglycerides
14...Hyperlipidemia Clinical Trials Resolve Non-statin Drugs Investigations
15...Clinical Trials Resolve Hyperlipidemia Non-statin Drugs Investigations
16...Investigations Clinical Trials Resolve Hyperlipidemia Non-statin Drugs
17...Work Plan Atorvastan 4-week Trial then Add Ezetimibe
18...Karen Coordinated Communications Starting Trial Atorvastatin
19...Clinical Trial PCSK9 VA Conctact UCSF Resolve Hyperlipidemia
20...Ezetimibe (Zetia) with Atorvastatin Promising Lower CVD Risk Hyperlipidemia
21...Atorvastatin with Ezetimibe (Zetia) Promising Lower CVD Risk Hyperlipidemia
............Safety and Efficacy of Ezetimibe Added to Atorvastatin Versus
............Up Titration of Atorvastatin to 40 mg in Patients >=65 Years
............of Age (from the ZETia in the ELDerly [ZETELD] Study)
........Clinical Investigation and Reports
........Effect of Ezetimibe Coadministered With Atorvastatin in
........628 Patients With Primary Hypercholesterolemia
22...Atorvastatin 10 Ezetimibe 10 HDL 5% Increase TG 30% LDL-C 50% Reduction
23...HDL 5% Increase TG 30% LDL-C 50% Reduction Atorvastatin 10 Ezetimibe 10
24...Side Effects Atorvastatin 10 MG with Ezetimibe 10 MB
25...Ezetimibe 10 MB Side Effects with Atorvastatin 10 MG
26...Side Effects Ezetimibe 10 MB with Atorvastatin 10 MG
27...VA Confirm Work Plan Atorvastan 4-week Trial then Add Ezetimibe
28...Notify Doctor Alba Implement Prescription Atorvastatin Manage Cholesterol
29...Research Arterialsclorsis Cornorary Artery Disease and Cholesterol
30...High LDL-C Low LDL-P Discordance Lowers Risk Shown by TG HDL-C Ratio 2
....1...Tim Russert's Fatal Heart Attack Was Preventable, He Followed
........Antiquated Advice
31...Exercise Russert Overweight Died Low HDL High TG Despite LDL 70
32...Russert Died Low HDL and High TG Several Years Excess Weight
33...Triglycerides High HDL Low Russert Died CVD with Low LDL Excess Weight
34...HDL Low Triglycerides High Russert Died CVD with Low LDL Excess Weight
35...Exercise Bike Failed Russert Overweight
36...Low-Carb Diet Lower Triglycerides Large LDL Particle Size Protective
37...LDL 246 Cholesterol 326 Healthy with TG 77 HDL 65
38...LDL-P Size Large Fluffy Protective with HDL 65 and TG 77
39...Protective LDL Particle Large Size Fluffy with HDL 65 and TG 77
40...Low Carb Diet TG/HDL Ratio 2 Lower Risk Arterialsclorosis CVD
41...TG/HDL Ratio 2 Low Carb Diet Lower Risk Arterialsclorosis CVD
42...Ratio TG/HDL 2 Low Carb Diet Lower Risk Arterialsclorosis CVD
43...Cholesterol Bound Atherogenic Lipoproteins Causes Aterialsclorosis
44...Triglycerides Indicate Small LDL Particle Size High Risk CVD
45...High LDL Particle Count Indicates Cholesterol Depleted LDL
46...Artiarialsclorosis Caused by High Number LDL Particles LDL-P
47...Cholesterol in LDL Particles Not Causative Artialsclorosis
48...LDL-C Low May Indicate High Risk CVD Arterialsclorsis Discordance
49...Discordance Low LDL-C May Indicate High Risk CVD Arterialsclorsis
50...ApoB LDL-P Both Predict Risk CVD Arterialsclorsis Better than LDL-C
51...LDL-P Size Small 300% Greater Risk CVD Large LDL-P Cholesterol Protective
52...Large Fluffy LDL Particles Protective 300% Lower Risk than Small Dense LDL
53...Lipid Panal ApoB LDL-P Assess CVD Risk Better than LDL-C Misleading
54...CVD Risk High LDL-P High and LDL-C Low Metabolic Syndrome Means Overweight
55...LDL-P High and LDL-C Low High Risk CVD Metabolic Syndrome Means Overweight
56...Metabolic Syndrome Means Overweight LDL-P High and LDL-C Low High Risk CVD
57...LDL-C Lower Statins Misleading Don't Lower LDL-P ApoB
58...Statin Medication Lowers LDL-C More than LDL-P Misleading
59...Niacin Low-Carbohydrate Diet Reduces Triglycerides Lowers LDL-P
60...Triglycerides Lower Exercise Weight Loss Fibrates Niacin
61...LDL-P Lowered by Exercise Low-Carbohydrate Diet Reduces Triglycerides
62...Carbohydrate Restriction Lowers LDL-P by Lowering Triglycerides
63...Exercise Lowers LDL-P
64...LDL-C Limited Value Misleading Risk Assessment Arterialsclorosis
65...Metabolic Syndrome TG High HDL Low LDL-P ApoB High LDL-C Low Misleading
66...LDL-C Low Misleading Metabolic Syndrome TG High HDL Low LDL-P ApoB High
67...Lipid Panal ApoB LDL-P Assess CVD Risk Better than LDL-C Misleading
68...CVD Risk High LDL-P High and LDL-C Low Metabolic Syndrome Means Overweight
69...LDL-P High and LDL-C Low High Risk CVD Metabolic Syndrome Means Overweight
70...Metabolic Syndrome Means Overweight LDL-P High and LDL-C Low High Risk CVD
71...Metabolic Syndrome Overweght Obese TG/HDL Ratio > 3.5
72...Overweght Metabolic Syndrome TG/HDL Ratio > 3.5 Obese
73...Obese Metabolic Syndrome Overweght TG/HDL Ratio > 3.5
74...TG/HDL Ratio > 3.5 Apply When LDL-P ApoB Not Available Lipid Panel
75...Diagram LDL Particle Count Higher Triglycerides Rich/Cholesterol Depleted
76...Attia Article Explain Concordant Discordant LDL Particles
77...Cholesterol Essential for Life Background Articles Doctor Attia
78...Eating Cholesterol Excreted Not Major Factor Arterialsclorosis CVD
79...Cholesterol Eating Excreted Not Major Factor Arterialsclorosis CVD
80...Eating Cholesterol Little Effect on Health and Lipid Blood Tests
81...LDL HDL Lipoproteins Transport Cholesterol Triglycerides
82...Cholesterol Triglycerides Transported Lipoproteins HDL LDL
83...Triglycerides Cholesterol Transported Lipoproteins HDL LDL
84...Lipoproteins Cholesterol Triglycerides Transported HDL LDL
85...Apoprotiens ApoB in LDL and ApoA-I in HDL Produced in Liver
86...ApoB in LDL and ApoA-I in HDL Apoprotiens Produced in Liver
87...Lipid Panel Cholesterol Total, Triglycerides, HDL LDL-C Estimated
88...LDL-P Test Count Particles and Measure Particle Size - NMR LipoProfile
89...NMR LipoProfile Test Count LDL-P Particles and Measure Particle Size
90...Lipid Test NMR LipoProfile Count LDL-P Particles and Measure Particle Size
91...LDL Particle Count Lower Reduce Risk Arterialsclorosis
92...Arterialsclorosis ApoB LDL Particle Penetrates Endothelial Artery Lining
93...Endothelial Artery Lining ApoB LDL Particle Penetrates Arterialsclorosis
........2...Concept #8 - Why is it necessary to measure LDL-P, instead of just LDL-C?
94...LDL-P 1000 nmol/L Target Reduce Risk CVD Event
95...CVD Risk Lowest Discordant LDL-P Low 1060 LDL-C High >= 100
96...Atherosclerosis Lowest CVD Risk LDL-P Low LDL-C High Discordant
97...LDL-P Low LDL-C High Discordant Lowest Risk CVD Atherosclerosis
98...Discordant LDL-P Low LDL-C High Least Risk CVD Arterialsclorsis
99...Frequency Discordance About 20% LDL-P Low LCL-C High
100...Discordant Population 20% LDL-P 1060 "Low" LDL-C >= 100 "High"
101...Doctors Do Not Know Some People Elevated LDL-C Low Risk CVD
........The straight dope on cholesterol - Part V (5)
102...TG/HDL Ratio with TG 100 and HDL > 50 Low CVD CAD Risk
103...CVD Risk Triglyceride HDL Ratio Substitute to Measure LDL-P
104...Triglyceride HDL Ratio Substitute Measure LDL-P Assess CVD Risk
105...TG/HDL Ratio 2 Indicates Dense/Small LDL Particle Size
106...LDL Particle Size Assessment Triglycerides/HDL Ratio
107...Exercise HDL Increase with Orange and Cranberry Juice
108...Orange Juice Exercise Increase HDL and Cranberry
109...HDL Exercise Increase with Orange and Cranberry Juice
110...Orange Juice Increased HDL 21% 750 ML Per Day Over 4 Weeks
111...HDL 21% Orange Juice Increased 750 ML Per Day Over 4 Weeks
112...Exercise Jim Fixx Infrequent Caused Heart Attack Running 10 Miles
113...Fixx Jim Myocadial Infarction Heart Attack Running 10 Miles
114...Jim Fixx Died CVD While Running 10 Miles Training for Marathons
115...Russert HDL Low TG High BP Elevated Overweight Enlarged Heart
116...Russert High TG Low HDL High Blood Pressure Overweight
117...Risk Factors Cardiovascular Disease Blocked Artery Heart Attack
118...Cardiovascular Disease Blocked Artery Heart Attack Risk Factors
119...Arterialsclorosis Myocardial Infarction Heart Attack Risk Factors
120...Russert CT Score 210 Should be 0
121...Artherosclerosis Coronary CTA and IVUS Measure Plaque
122...Coronary CTA and IVUS Arterialsclorsis Plaque Measure
123...IVUS and Coronary CTA Arterialsclorsis Plaque Measure
............Coronary Atherosclerosis Imaging by Coronary CT Angiography
124...CT Assess Arterialsclorsis Plaque Difficult Requires Equip Expertise
............Assessment of coronary plaque progression in coronary
............computed tomography angiography using a semiquantitative score.
125...Exercise HDL Increase Aerobic Long Duration Lose Weight
126...HDL Increase Exercise Aerobic Long Duration Lose Weight
127...Aerobic Exercise Long Duration Lose Weight Increase HDL
128...Weight HDL Increase Lose Weight Aerobic Long Duration Exercise
129...HDL Lose Weight Aerobic Exercise
130...HDL Increased with Drugs Caused Increased Cardiac Risk
131...Processed Food Chips Donuts High Trans Saturated
132...LDL Increase Saturated and Trans Saturated Acids
133...Saturated and Trans Saturated Acids Increase LDL
134...Trans Saturated and Saturated Acids Increase LDL
................Trans Fatty Acids and the Heart
................They're everywhere, and they may be worse than lard
135...Trans Acids Decrease HDL and Increase LDL Cholesterol
136...Test LDL Small Dense Particle Size CAD Patients
137...Triglycerides Lower Exercise Weight Loss Niacin Fibrates Increase LDL-P Size
138...Weight Loss Exercise Niacin Fibrates Reduce Triglycerides Increase LDL-P Size
139...Exercise Weight Loss Niacin Fibrates Reduce Triglycerides Increase LDL-P Size
140...Niacin Exercise Weight Loss Fibrates Reduce Triglycerides Increase LDL-P Size
141...Statins Do Not Change Particle Size Overlooks CVD Risk TG 70 - 40
142...LDL Particle Size Measurement TG > 70 140 Assess CVD Risk
143...CVD Risk Small Dense LDL Need Measurement LDL Particle Size
144...LDL-P Measurement Needed Assess CVD When TG > 70 140
145...TG > 70 140 Direct Measurement LDL-P Size for Small Dense LDL
146...Cholesterol Essential for Life Triglycerides Deliver Energy to Muscles
147...Triglycerides Deliver Energy to Muscles Cholesterol Essential for Life
148...Diagram Compare LDL TG Dense and LDL Cholesterol Fluffy Particles
149...Genetic Variability Tolerates Different Dietary Content
150...Carbohydrate/sugar Diet Cause Dangerous Small Dense LDL Particles
151...Exercise Lowers Triglycerides Strengthens Cardiovascular Function
152...Triglycerides Eggs Decrease Improve Control Arterialsclorosis Risk
153...HDL Eggs Increase Quantity Quality Control Arterialsclorosis Risk
154...Arterialsclorosis CVD Risk Eggs Increase HDL Function Triglycerides Lower
155...Eggs HDL Rise Triglycerides Decrease Improve Control CVD Risk
156...LDL Pattern A > 250 AN LDL Pattern B 250 AN Penetrate Endothelial Lining Artery
157...HDL Particle Count Increased with Exercise Lowers CVD Risk
158...CVD Risk Requires Measuring HDL Particle Count with NMR Testing
159...Exercise HDL Particle Count Decrease Lowers CVD Risk
160...HDL Exercise Increase Particle Count Lowers CVD Risk
161...Medication Raises HDL Cholosterol But Not HDL Particle Count
162...HDL Large Particle Size Lowers CVD Risk
163...HDL Very Large Particle Size Increases CVD Risk
164...Regression Arterialsclerosis Occurs with Lower LDL and Higher HDL
165...Arterialsclerosis Regression Occurs with Lower LDL and Higher HDL
........Rapid regression of atherosclerosis:
166...CT & Intravasuclar Ultrasonography IVUS Quantify Arterial Plaque Change
167...IVUS Intravasuclar Ultrasonography CT & Quantify Arterial Plaque Change
168...Regression Atherosclerosis Measure Plauqe with CT and IVUS Technology
169...Atherosclerosis Regression Measure Plauqe with CT and IVUS Technology
170...Regression Arterialsclerosis Plaque 6.8% Rosuvastatin High Dose 18 Months
171...Statin High Dose 18 Months Lower LDL-C 60 and > 50% Reduce Plaque 6.8%
172...Rapid Regression Atherosclorotic Plaques Elevated HDL and EPCs
173...Regression Atherosclerosis Plaque Caused By Elevation HDL and Lower LDL
174...HDL Elevation and Lower LDL Could Cause Rapid Atherosclerosis Plaque Regression
175...Atherosclerosis Plaque Regression Caused By HDL Elevation and Lower LDL Could
176...Regression Arterialsclorosis Plaque Occurs Lower LDL-P Increased HDL
177...Prevention Reversal Atherosclerosis Plaque
178...Regression Atherosclerosis Plaque Prevention
179...Atherosclerosis Regression Plaque Prevention
........The prevention and regression of atherosclerotic plaques: emerging treatments
180...Atherosclerosis Test Imaging Intravascular Ultrasound IVUS
181...IVUS Intravascular Ultrasound Atherosclerosis Test Imaging
182...Atherosclerosis Test Imaging Carotid Artery Intimal-Medial Thickness CIMT
183...CIMT Carotid Artery Intimal-Medial Thickness Atherosclerosis Test Imaging
184...Exercise Vigorous 150 Minutes Moderate 75 Minutes Per Week - AHA
185...Weight Loss Increases HDL Lowers Blood Pressure Aided Exercise
186...Exercise Weight Loss Aids HDL Increase and Lowers Blood Pressure
187...Exercise Lowers Triglycerides LDL-P Apo B Increases HDl Decrease Plaque
188...Atorvastatin 80 Ezetimibe 10 Yield Atherosclerosis Regression 0.4%
189...Triglycerides Lower Endurance Exercise Increase HDL
190...Endurance Exercise Increase HDL Lowers Triglycerides
191...Exercise HDL Increase Triglyceride Lower Endurance Training
192...HDL Increase Endurance Exercise Lowers Triglycerides
193...Hypoalphalipoproteinemia - Low HDL 35
194...HDL Low Biggest Risk CVD CAD Heart Attack
195...VA HDL Intervention Study Found HDL Strongest Protection Against CVD
196...Exercise Genetic Requirement Human Cardiovascular Survival
197...Endurance Exercise Effects Cardiovascular Endothelial Function
198...Exercise Recovery Cardiovasular Disease Endothelial Function
199...Cardiovasular Disease Exercise Recovery Endothelial Function
200...Atherosclerosis Regression EPCs Increase Exercise Signals Bone Marrow
201...Regression Atherosclerosis EPCs Increase Exercise Signals Bone Marrow
202...EPCs Produced Bone Marrow Increased Exercise Repair Endothelial Lining
203...Exercise Causes Atherosclerosis Regression for Endurance Training
204...Endothelial Cells Regression Atherosclerosis Integrated HDL Effects
205...HDL EPC Elevated Causes Rapid Regression Atherosclerosis
206...EPC HDL Elevated Causes Rapid Regression Atherosclerosis
207...Atherosclerosis Elevated HDL EPC Causes Rapid Regression
........An integrated approach for the mechanisms responsible for
........atherosclerotic plaque regression
208...HDL Controversy Drug Induced Fails Regress Atherosclerosis Plaque
209...Controversy HDL Drug Induced Fails Regress Atherosclerosis Plaque
........Raising HDL Cholesterol: The Controversy

ACTION ITEMS.................. Click here to comment!

1...What about CT test to assess level of plaque build up due to LDL 249,
2...What causes plaque "rupture" mentioned in last sentence of this para?

CONTACTS 

SUBJECTS
VA Commend Great Care Recover CABG 4x Heart Surgery 091022 Prevent C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
0803 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
0803 -    ..
0804 - Summary/Objective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
0805 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
080501 - Follow up ref SDS 44 0000. ref SDS 41 0000.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
080502 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080503 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080504 -            [On 131210 received letter from Doctor Alba asking about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
080505 -            progress taking Atorvastatin 40 mg, and requesting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
080506 -            submission of pending issues for next meeting. ref SDS 46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
080507 -            HY6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080509 -             ..
080510 -            [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
080511 -            submits pending issues to discuss during meeting on 131219,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
080512 -            ref SDS 47 8N50, and lists TG/HDL-C ratio and LDL-P issues.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
080513 -            ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
080515 -             ..
080516 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
080517 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
080518 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
080519 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
080520 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
080521 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
080522 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
080523 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
080524 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080525 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
080527 -             ..
080528 -            [On 151019 0930 Radiology report on CCTA test performed on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
080529 -            151019, indicates calcification in original bypassed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080530 -            arteries has increased since CABG +4 surgery on 091022;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
080531 -            seems conflicting with this research theorizing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
080532 -            atherosclerosis plaques regress rapidly with elevated HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
080533 -            and EPCs. ref SDS 69 J14N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
080535 -             ..
080536 -            [On 151019 0930 an undated addendum was added to report                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
080537 -            on CCTA test on 151019, that clarifies findings and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
080538 -            impressions by establishing CCTA found no evidence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
080539 -            plaque, stenosis, occlusion of any kind or amount.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
080540 -            ref SDS 69 SU4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
080541 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080542 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080543 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
080545 -  ..
0806 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
0807 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
0808 - Background                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
0809 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
0810 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
081001 - Lab on 131015, showing cholesterol remained high, 131015 0724,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
081002 - ref SDS 38 BE6O, conflict with increased exercise and weight loss,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
081003 - discussed in the letter to the medical team yesterday on 131016 1632.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081004 - ref SDS 39 IW57                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081006 -  ..
081007 - On 131017 1000 VA medical chart Progress Notes assessment report                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
081008 - patient status CAD stable, asymptomatic. hyperlipidemia not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081009 - controlled. ref SDS 40 T24N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
081011 -  ..
081012 - On 131017 1000 Doctor Egan proposed referring patient for clinical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
081013 - trial to reduce cholesterol with new "targeted" drugs. ref SDS 40 179N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
081015 -  ..
081016 - On 131017 1000 VA medical chart Progress Notes assessment report                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
081017 - patient status hyperlipidemia not controlled, ref SDS 40 PSXT; Doctor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081018 - Egan makes referral to SF VA Medical Center for consult on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
081019 - participation clinical trials, ref SDS 40 EU9F, with experimental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
081020 - agents such as AMG 145 and REGN 727 to resolve multiple statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
081021 - intolerances. ref SDS 40 CN4H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
081023 -  ..
081024 - On 131103 received letter from VA SF Medical Center scheduling meeting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081025 - on 131121 1000, to consider clinical trial for lowering cholesteral.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
081026 - ref SDS 41 YT4N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081027 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081028 -            Thursday November 21, 2013 1000 METAB-FELLOW-THRUSDAY Clinic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081030 -  ..
081031 - On 131112 New York Times published several articles reporting that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081032 - day before on 131113, American Heart Association published new                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
081033 - guidelines for treating CAD patients that expand use of statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
081034 - medication regardless of cholesterol levels, ref SDS 42 0001, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
081035 - further raise the LDL 70 to LDL 190, as a target for cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
081036 - risk. ref SDS 42 CW6H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081038 -  ..
081039 - On 131114 New York Times published several articles reporting that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081040 - day before on 131113, American Heart Association published new                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
081041 - guidelines for treating CAD patients. ref SDS 43 SH6G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081043 -  ..
081044 - On 131121 1000 meeting with Doctor Diana Alba, Va San Francisco                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081045 - Medical Center prescribes Atorvastatin 10 MG 4 weeks. ref SDS 44 HY6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081047 -  ..
081048 - On 131121 1000 at 1125 meeting with Karen and Doctor Shunk, Va San                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
081049 - Francisco Medical Center seemed to support Doctor Alba's prescription                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081050 - for Atorvastatin 10 MG 4 weeks; further suggested trying Chia seeds to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081051 - lower cholesterol without medication. ref SDS 44 MS7G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081052 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081053 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081054 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081055 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081057 -  ..
0811 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
0812 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
0813 - Progress ref SDS 0 MN98                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
0814 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
081401 - Hyperlipidemia Not Controlled Cholesterol Elevated Despite Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
081402 - Cholesterol Elevated Despite Exercise Discuss Clinical Trial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
081403 - Clinical Trial Considered Lower Cholesterol Without Statin Drugs                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
081404 - 
081405 - Follow up ref SDS 44 HY6O, ref SDS 41 VY6H.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
081406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081407 - Submitted letter to Karen saying...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
081408 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081409 -    1.  Subject:  VA Excellent Care Post CABG x4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081410 -        Date:  Mon, 25 Nov 2013 01:04:55 -0800                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
081419 -         ..
081420 -    2.  Thanks for meeting briefly in your office with Doctor Shunk,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
081421 -        this past Thursday on 131121. ref SDS 44 MS7G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
081426 -         ..
081427 -    3.  It's always a pleasure to thank the VA SF Medical Center for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
081428 -        great care, beginning with your timely, thorough coordination.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081429 -        Doctor Shunk and his Cath Lab team provided critical guidance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
081430 -        on 091021.  I'm still amazed that Dennis arranged on moment's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
081431 -        notice to play Simon and Garfunkel's famous album from the 70s,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081432 -        while Doctor Shunk explained... "Rod, let me show you what I'm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081433 -        seeing here."  It's a wonderful story for the VA. [...reported                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
081434 -        on 091021 0716. ref SDS 4 025B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081436 -         ..
081437 -    4.  Thanks for reporting and congratulations to Doctor Tseng taking                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081438 -        over for Doctor Ratcliffe, as Chief of Surgery. [...reported on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
081439 -        131121 0930. ref SDS 44 NQ31...].  They were both instrumental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
081440 -        in my surgery on 091022, ref SDS 5 PQWU, leading the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
081441 -        Cardiothoracic team - Neal, Paula, KC, Joe and others.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
081442 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081443 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
081444 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
0815 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Lipids Triglycerides TG Rise HDL Declines CAD CVD Risk Rises Conflic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
3103 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
310401 -  ..
310402 - Lipid Lab LDL HDL TG Conflicts Hiking Weight Loss                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310403 - Lab Lipid LDL HDL TG Conflicts Hiking Weight Loss                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310404 - Cholesterol Elevated Despite Exercise Weight Loss                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310405 - Hyperlipidemia Not Controlled Cholesterol Elevated Despite Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310406 - 
310407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310408 -    5.  Doctor Egan's Progress Notes on 131017, report the patient has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310409 -        made a strong recovery from CABG, under his guidance at the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310410 -        Martinez Clinic, ref SDS 40 UU7J, underscored by climbing Half                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310411 -        Dome a few weeks ago on 130918. ref SDS 37 0001                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310413 -         ..
310414 -    6.  This reflects increased exercise, since surgery in 2009.  If                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310415 -        time permits, you can see patient history on diet medication                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310416 -        exercise and vitals the past 2 years, that shows hiking 14.2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310417 -        miles per day for 3 days last week, and completed with 11 mile                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310418 -        dailies including today. [...see case study on 120101 0900.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310419 -        ref SDS 15 L25L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310421 -         ..
310422 -    7.  Yesterday, I did my fastest time ever [...160 minutes...] for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310423 -        11 miles. ref SDS 15 8A9A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310424 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310425 -            [On 120101 case study show on 131223 did 11 mile route in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
310426 -            159 minutes - best time ever. ref SDS 15 839G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310428 -         ..
310429 -    8.  At this time, I feel very healthy and functional.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
310431 -         ..
310432 -    9.  Before meeting with you and Doctor Shunk, I met with Doctor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310433 -        Diana Alba in the Metab-Fellow-Thursday Clinic. ref SDS 44 6H6K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310434 -        She is listed with the UCSF Dep of Medicine, Division of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310435 -        Endoncrinology and Metabolism.  The meeting was arranged by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310436 -        Doctor Egan to begin a process finding a clinical trial or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310437 -        other path for reducing risks of hyperlipidemia, with LDL 249                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310438 -        in the lab on 131015. ref SDS 38 BE6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310439 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310440 -            [...below on 131125 0005 at 1516 receive letter from Karen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310441 -            saying she will contact UCSF for clinical trials on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310442 -            lowering cholesterol. ref SDS 0 V163                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310444 -             ..
310445 -            [...below on 131125 0005 at 1923 follow letter to Karen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310446 -            notifies VA SF Medical Center patient objective to find                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310447 -            clinical trials or other means that reduce risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
310448 -            arterialsclorosis without using statin medications.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310449 -            ref SDS 0 YU5X                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310451 -         ..
310452 -   10.  You can see patient history on the lipid panel going back to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310453 -        2006, there appears to be inverse correlation between healthy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310454 -        diet, rising aerobic exercise 200-350 miles per month, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310455 -        rising LDL. ref SDS 38 BE9O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
310457 -         ..
310458 -   11.  In 2006, I was hiking 50 miles per month; by 2009, I increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310459 -        this to about 100 miles per month, yet still weighed 205.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310460 -        During that period without medication, cholesterol fell from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310461 -        LDL 192 to LDL 164.  In 2010, Doctor Sandhu, Primary Care in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310462 -        the Martinez Clinic initiated treatment with Simvastatin,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310463 -        applying CAD protocol [...reported on 100104 0930. ref SDS 7                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310464 -        FG6K...].  LDL dropped to 96 [...after doubling dose to 40 mg,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310465 -        reported on 100721 0800. ref SDS 8 RP4F...], but then                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310466 -        increased back to over 200 [...reported on 111117 1415.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310467 -        ref SDS 14 2A4G...], i.e., doubled, while causing severe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310468 -        myopathy in the left shoulder.  Doctor Egan in Cardiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310469 -        continued Simvastatin, but then switched to Rosuvastatin to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310470 -        avoid side effects, and to try lowering cholesterol to below                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310471 -        LDL 70. [...reported on 110817 1030. ref SDS 13 DG36...],                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310473 -         ..
310474 -   12.  As Doctor Egan reports on 131017, ref SDS 40 E47G, severe side                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310475 -        effects required ending Rosuvastatin on 121206, see line                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310476 -        100401. ref SDS 25 I05F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310478 -         ..
310479 -   13.  Increased hiking the past year to 200-350 miles per month has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310480 -        reduced weight about 30 pounds to 170. [...see patient history                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310481 -        hiking 11 miles per day 7 days a week, beginning on 130427,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310482 -        shown in patient history referenced above in para 6,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310483 -        ref SDS 0 UK42, case study on 120101 0900. ref SDS 15 F35N...].                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310484 -        Still working on getting to 165 or possibly 160.  Have reached                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310485 -        167 numerous times, but have not held that number.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310486 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310487 -            [On 131216 0028 letter notified VA again that hiking                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310488 -            increased to 11 miles per day, ref SDS 48 6T49, citing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
310489 -            patient history, beginning on 130427, in case study on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310490 -            120101 0900. ref SDS 15 F35N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
310492 -         ..
310493 -   14.  Since cholesterol has increased, instead of declined as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310494 -        expected from increasing exercise and weight loss by orders of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310495 -        magnitude, this presents a question of why it was much lower                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310496 -        previously with much less exercise and higher weight and no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310497 -        medication?  Is this is common from merely aging 7 years?  If                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310498 -        so, then it might be reasonable to risk severe adverse side                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310499 -        effects taking medication in order to lower LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
310501 -         ..
310502 -   15.  Otherwise, might there be tests to determine what is causing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310503 -        LDL to rise, when it should be falling, and similarly, HDL is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310504 -        falling, when it should be rising, based on patient history of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310505 -        hiking 200-350 miles per month and weight loss of 30 pound the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310506 -        past 6 months or so?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310507 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310508 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310509 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310510 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310511 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310512 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310513 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310514 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310515 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310516 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310517 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310519 -         ..
310520 -   16.  Could excessive exercise be stimulating production of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310521 -        cholesterol?  Could past medications have caused damage that is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310522 -        making cholesterol rise in conflict with patient history?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310524 -         ..
310525 -   17.  During discussion in your office on 131121, there was an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310526 -        observation that the patient is simply unlucky having high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310527 -        cholesterol that does not decline with increased exercise and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310528 -        weight loss.  Perhaps so, but this is not evident from patient                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310529 -        history beginning in 2006, as shown in the Lipid chart on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310530 -        131015? ref SDS 38 BE9O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310531 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310532 -            [...below on 131125 0005 research found representation that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
310533 -            increasing cholesterol with increased exercise indicates                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310534 -            body malfunction of liver that requires remedy to restore                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310535 -            normal production of cholesterol by the liver. ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310536 -            VT41                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310538 -             ..
310539 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310540 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310541 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310542 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310543 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310544 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310545 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310546 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310547 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310548 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310549 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310551 -  ..
310552 - Wicked Problems Good Condition Hiking Weight Loss Masks Poor Health                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310553 - Good Condition False Positive Hiking Weight Loss Masks Poor Health                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310554 - Hiking Good Condition Masks Poor Health CVD with High LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310555 - False Positive Patient Good Condition Hiking Masks Rising CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310556 - 
310557 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310558 -   18.  I am concerned that seemingly excellent health shown by rising                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310559 -        physical capacity may be a false positive, masking failing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310560 -        health due to rising arteriosclerosis.  Prior to CABG in 2009,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310561 -        I had minor chest pains beginning in 2003, that only occurred                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310562 -        when hiking up the first hill at Lafayette reservoir on a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310563 -        3-mile route.  When one day minor pain persisted for an entire                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310564 -        lap, this signal was reported to Doctor Lee, then in Martinez                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310565 -        EGD Dep, who made referral to Doctor Egan in Cardiology.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310566 -        Since, surgery in 2009, and particularly the past 12 months,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310567 -        there has been no inkling of chest pain of any kind, and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310568 -        body is placed under severe duress for 3 plus hours 7 days a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310569 -        week.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310570 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310571 -            [...below on 131125 0005 research found patient with high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
310572 -            LDL 249 was "healthy" with low risk for arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310573 -            CVD because HDL > 50 and triglycerides < 100 so TG/HDL
310574 -            ratio below 2, indicating LDL particle size is "protective"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310575 -            because it is "large and fluffy" that cannot penetrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310576 -            endothelial lining of artery walls. ref SDS 0 6P4N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
310578 -             ..
310579 -            [On 140116 0814 letter to medical team cites research that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310580 -            seems to indicate labs can be ordered to test patients for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310581 -            discordance between high LDL-C and low LDL-P that presents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310582 -            lowest risk for arterialsclorosis, CVD, mycardial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310583 -            infarction. ref SDS 52 FW4K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310585 -             ..
310586 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310587 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310588 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310589 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310590 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310591 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310592 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310593 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310594 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310595 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310597 -             ..
310598 -            [On 140204 1236 VA letter maintains patient lab on 131015                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
310599 -            showing LDL-C 249, and calculated non-HDL 271 represent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310600 -            "unhealthy" lipid profile for patient with history of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310601 -            coronary artery disease/cardiovascular disease (CAD/CVD).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310602 -            ref SDS 56 6U4L  This assesement aligns with NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310603 -            showing range for non-HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310604 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310606 -         ..
310607 -   19.  If the patient foregoes statin treatment at this time in order                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310608 -        to avoid side effects, might it be expected to get similar                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
310609 -        notice over the next 6 years that build up in the arteries is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310610 -        occurring that may cause a blockage, as occurred during 2003 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310611 -        2009?  In other words, if treatment with statins had been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310612 -        started in 2003, and if that was effective, would it have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310613 -        likely prevented needing CABG surgery on 091022?  If so, is it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310614 -        reasonable now to continue subjecting the body to high duress,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310615 -        and defer medication until minor symptoms begin, as occurred                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310616 -        previously in 2003?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
310617 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310618 -            [...below on 131125 0005 CT imaging can determine presence                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310619 -            of arterialsclorosis plaque in the circulatory system, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310620 -            measure progression toward blockage. ref SDS 0 N73K and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310621 -            summarized. ref SDS 0 278M                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310623 -         ..
310624 -   20.  Maybe a study could be done to test the theory that increasing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310625 -        exercise increases tolerance for cholesterol, even at elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310626 -        levels, as in this case.  We have 4 years without symptoms,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310627 -        much with elevated cholesterol.  Would the medical team feel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310628 -        the patient is at too great a risk to try for another 4 years?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310629 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310630 -            [...below on 131125 0005 research indicates high LDL lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310631 -            test results, like LDL 249 in lab on 131015 0724,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310632 -            ref SDS 38 BE6O, are well tolerated and even healthy, if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310633 -            discordant, ref SDS 0 OB7L, with LDL-P < 1000, ref SDS 0
310634 -            K68N, if LDL particle size is large, and this occurs when                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310635 -            triglycerides < 100 and HDL > 50, ref SDS 0 338N; exercise
310636 -            increases HDL, ref SDS 0 W76M, and lowers triglycerides.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310637 -            ref SDS 0 QP9F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310639 -             ..
310640 -            [On 140116 0814 letter to medical team cites research that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310641 -            seems to indicate labs can be ordered to test patients for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310642 -            discordance between high LDL-C and low LDL-P that presents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
310643 -            lowest risk for arterialsclorosis, CVD, mycardial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310644 -            infarction. ref SDS 52 FW4K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310646 -             ..
310647 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310648 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310649 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310650 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310651 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310652 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310653 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310654 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310655 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310656 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310658 -         ..
310659 -   21.  Initially, this question seems resolved from patient history of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310660 -        failing, i.e., needing surgery with relatively low levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310661 -        cholesterol - LDL below 300.  However, prior failure occurred                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
310662 -        hiking only 100 miles per month, and weighing 200+.  Now,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310663 -        hiking is at 200-350 miles per month, and weight is 170 after a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310664 -        hike - does the medical team view this as a material change?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310665 -        If we increased to 400 miles per month, would that make a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310666 -        difference sufficient to avoid taking medication with severe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310667 -        adverse side effects?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310669 -  ..
310670 - Research indicates high LDL-C cholesterol per se does not cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310671 - arterialsclorsis - coronary artery disease (CAD) - cardio vascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
310672 - disease CVD).  For example, Jim Fixx, a public voice for aerobic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310673 - running exercise, died on the side of the road on 1984 July 20, due to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310674 - CVD while running 10 miles daily.  Further, low LDL below 70 is not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310675 - sufficient to maintain cardio vascular health.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
310677 -             ..
310678 -            [...below on 131125 0005 Tim Russert died with CVD despite                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310679 -            LDL < 70, but HDL < 40. ref SDS 0 W26M
310681 -             ..
310682 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310683 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
310684 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
310685 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
310686 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
310687 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310688 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310689 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
310690 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310691 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
310692 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310693 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310694 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
310695 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
3107 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Atorvastatin 40 MG Started 4-week Trial Test Side Effects Before Add                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
5503 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
550401 -  ..
550402 - Atorvastatin Prescribed with Ezetimibe Increase HDL Lower Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
550403 - Hyperlipidemia Clinical Trials Resolve Non-statin Drugs Investigations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
550404 - Clinical Trials Resolve Hyperlipidemia Non-statin Drugs Investigations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
550405 - Investigations Clinical Trials Resolve Hyperlipidemia Non-statin Drugs                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
550406 - 
550407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550408 - Letter to medical team continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
550409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550410 -   22.  On Thursday, 131121, Doctor Alba prescribed taking Atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550411 -        for 4 weeks, and then meet again to evaluate continuing or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
550412 -        trying other non-statin drugs, which she will be researching,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550413 -        including clinical trials.  She cited contacts at UCSF.  During                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550414 -        the meeting in your office, Doctor John Kane was suggested for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550415 -        consulting in this case, since he is the Director of the Adult                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550416 -        Lipid Clinic at UCSF.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
550418 -         ..
550419 -   23.  I assume Doctor Alba and her team will order a lab in 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550420 -        to evaluate results taking Atorvastatin.  By chance, I saw                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
550421 -        Doctor Egan briefly at the Martinez VA Clinic on Friday, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550422 -        related meetings the day before at the Medical Center in San                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550423 -        Francisco. Explained progress and planning by Doctor Alba to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550424 -        investigate clinical trials without statins.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550425 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550426 -            [...below on 131125 0005 research finds ezetimibe (zetia)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
550427 -            for secondary drug recommended by "expert" to treat high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550428 -            risk CAD patient, ref SDS 0 XG4N, where LDL-P is high and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550429 -            discordant with low LDL-C, approximated by TG/HDL-C ratio <
550430 -            2, ref SDS 0 QS9F, which is shown by evidence in this case                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550431 -            from lab on 131015 0724. ref SDS 38 BE6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
550433 -         ..
550434 -   24.  To implement Doctor Alba's plan, I began taking Atorvastatin 40                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550435 -        mg Thursday evening, shown in patient history in case study on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550436 -        120101. ref SDS 15 0001                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550437 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550438 -            [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550439 -            140201- lab report shows LDL-P 861 and LDL-C 81, TG 68, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550440 -            61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
550441 -            results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
550442 -            ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
550443 -            131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550444 -            juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
550445 -            weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550446 -            for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550447 -            ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
550449 -         ..
550450 -   25.  Doctor Alba said she would submit a letter confirming her work                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550451 -        plan.  I gave her my email address, but so far have not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
550452 -        received her letter - maybe the address was quickly scribbled                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550453 -        incorrectly or misplaced.  We were rushed on Thursday.  Can you                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550454 -        please facilitate communication by forwarding this letter to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550455 -        Doctor Alba with a copy to me confirming the work plan?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
550457 -         ..
550458 -   26.  Doctor Alba may have prescribed Atorvastatin 10 mg, or 20 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550459 -        I have 40 mg pills on hand, and so started with them to test if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550460 -        this will move the numbers in 4 weeks.  I seem to remember one                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550461 -        of the side effects is "confusion and memory loss," but am not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
550462 -        sure, so treatment may already be taking affect (hopefully,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
550463 -        just joking).   In any case, Doctor Alba's letter will nail                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
550464 -        down all instructions, eliminating confusion, regardless of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
550465 -        memory loss.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
550467 -         ..
550468 -   27.  While this is a long letter, the short story is that the VA has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550469 -        been outstanding providing care and working with the patient to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
550470 -        enjoy a high quality of life.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
550472 -         ..
550473 -   28.  Happy holidays to all,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
550474 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550480 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550481 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
550482 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
5505 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Atorvastatin 10 MG 4-week Trial VA Treatment Plan Test Side Effects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
8603 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
8604 - 1516                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
860501 -  ..
860502 - Work Plan Atorvastan 4-week Trial then Add Ezetimibe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
860503 - Karen Coordinated Communications Starting Trial Atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
860504 - 
860505 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860506 - Received letter from Karen saying...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
860507 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860508 -    1.  Subject:  RE: VA Excellent Care Post CABG x4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
860509 -        Date:  Mon, 25 Nov 2013 14:39:29 -0800                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
860513 -         ..
860514 -    2.  Hello Rod,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
860515 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860516 -        I could not find Dr Albas email, so I forwarded your letter to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
860517 -        her attending so that he can forward it to her.  This was the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
860518 -        plan.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
860519 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860520 -            [...below on 131125 0005 at 1702 received letter from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
860521 -            Doctor Alba. ref SDS 0 I67O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
860523 -             ..
860524 -            [...below on 131125 0005 at 2006 letter responds to Karen,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
860525 -            reporting found Chia seeds for new dietary supplement that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
860526 -            may help control cholesterol, weight, and increase energy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
860527 -            ref SDS 0 057E                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
860529 -             ..
860530 -            [On 131210 received letter from Doctor Alba asking about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
860531 -            progress taking Atorvastatin 40 mg, and requesting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
860532 -            submission of pending issues for next meeting. ref SDS 46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
860533 -            HY6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860535 -         ..
860536 -    3.  Plan:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
860537 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860538 -        -Trial of  Atorvastatin 10 mg po daily, if tolerated we can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
860539 -        increase to maximum dose to reach LDL goal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
860541 -         ..
860542 -        -Start Zetia 10 mg po daily in 4 weeks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
860544 -  ..
860545 - Karen's letter confirms Doctor Alba's work plan during meeting at VA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
860546 - SF Medical Center on 131121 0930. ref SDS 44 6H6K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
860547 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860548 -            [below on 131125 0005 research finds ezetimibe (zetia) for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
860549 -            secondary drug recommended by "expert" to treat high risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
860550 -            CAD patient, ref SDS 0 XG4N, where LDL-P is high and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860551 -            discordant with low LDL-C, approximated by TG/HDL-C ratio <
860552 -            2, ref SDS 0 QS9F, which is shown by evidence in this case                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
860553 -            from lab on 131015 0724. ref SDS 38 BE6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
860555 -             ..
860556 -            [On 140430 0900 letter to VA notifies some minor dizziness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
860557 -            has begun while taking Atorvastatin 10mg with Ezetimibe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
860558 -            10mg. ref SDS 57 PU43                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
860559 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860560 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860561 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
860562 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
8606 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Atorvastatin 10 MG 4-week Trial VA Treatment Plan Test Side Effects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
AK03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
AK0401 -  ..
AK0402 - Clinical Trial PCSK9 VA Conctact UCSF Resolve Hyperlipidemia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
AK0403 - 
AK0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK0405 - Karen's letter continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK0407 -        -Regarding medical trial- PCSK9 is not available at this time,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
AK0408 -        but I will contact UCSF to determine if there are any ongoing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
AK0409 -        trials for lipid lowering medications and to see if Mr Welch                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
AK0410 -        could participate in any of them.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
AK0412 -  ..
AK0413 - Very helpful for Karen to make inquiries for trials to lower lipids,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
AK0414 - requested in the letter to Karen earlier this morning, and with copy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
AK0415 - to Doctor Alba, shown above. ref SDS 0 UK59                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
AK0416 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK0417 -            [...below on 131125 0005 at 1923 follow up letter to Karen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
AK0418 -            notifies VA SF Medical Center patient objective to find                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
AK0419 -            clinical trials or other means that reduce risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
AK0420 -            arterialsclorosis without using statin medications.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
AK0421 -            ref SDS 0 YU5X                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
AK0422 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK0423 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK0424 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
AK05 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Atorvastatin 10 MG Ezetimibe Zeita 10 MB Research Lowers Hyperlipide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
B903 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90401 -  ..
B90402 - Ezetimibe (Zetia) with Atorvastatin Promising Lower CVD Risk Hyperlipidemia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90403 - Atorvastatin with Ezetimibe (Zetia) Promising Lower CVD Risk Hyperlipidemia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90404 - 
B90405 - Research shows Zetia has been used successfully combined with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90406 - Atvorstatin, shown in paper at...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90408 -            American Journal of Cardiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90409 -            Volume 105, Issue 5 , Pages 656-663, 1 March 2010                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90411 -             ..
B90412 -            Safety and Efficacy of Ezetimibe Added to Atorvastatin Versus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90413 -            Up Titration of Atorvastatin to 40 mg in Patients >=65 Years                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90414 -            of Age (from the ZETia in the ELDerly [ZETELD] Study)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90415 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90416 -              http://www.ajconline.org/article/S0002-9149(09)02552-1/abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90418 -             ..
B90419 -            Few clinical studies have focused on the efficacy of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90420 -            lipid-lowering therapies in patients >=65 years of age.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90421 -            The percentage of change from baseline in low-density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90422 -            lipoprotein (LDL) cholesterol and the percentage of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90423 -            patients achieving prespecified LDL cholesterol levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90424 -            after 12 weeks of ezetimibe 10 mg plus atorvastatin versus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90425 -            up titration of atorvastatin were assessed in subjects ?65                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90426 -            years old with hyperlipidemia and at high risk of coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90427 -            heart disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90429 -             ..
B90430 -            After stabilization of atorvastatin 10-mg therapy, 1,053                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90431 -            patients, >= 65 years old, at high risk of coronary heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
B90432 -            disease, with and without atherosclerotic vascular disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90433 -            and a LDL cholesterol level that was not <70 or <100 mg/dl,
B90434 -            respectively, were randomized to receive ezetimibe added to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90435 -            atorvastatin 10 mg for 12 weeks versus up titration to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90436 -            atorvastatin 20 mg for 6 weeks followed by up titration to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90437 -            atorvastatin 40 mg for an additional 6 weeks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90439 -             ..
B90440 -            Ezetimibe added to atorvastatin 10 mg resulted in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90441 -            significantly greater changes at week 6 in LDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90442 -            (p <0.001), significantly more patients with
B90443 -            atherosclerotic vascular disease achieving a LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90444 -            cholesterol level of <70 mg/dl (p <0.001), and
B90445 -            significantly more patients without atherosclerotic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90446 -            vascular disease achieving a LDL cholesterol level of <100
B90447 -            mg/dl (p <0.001) at weeks 6 and 12 compared to atorvastatin
B90448 -            20 mg or atorvastatin 40 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
B90450 -             ..
B90451 -            In addition, ezetimibe plus atorvastatin 10 mg resulted in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90452 -            significantly greater changes at week 6 in total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90453 -            cholesterol, triglycerides, non-high-density lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90454 -            (HDL) cholesterol, apolipoprotein B (all p <0.001), and HDL
B90455 -            cholesterol (p = 0.021) compared with atorvastatin 20 mg                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90456 -            and significantly greater changes at week 12 in LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90457 -            cholesterol, non-HDL cholesterol, apolipoprotein A-I (p =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90458 -            0.001), total cholesterol, apolipoprotein B (p <0.030), and
B90459 -            HDL cholesterol (p <0.001) compared with atorvastatin 40
B90460 -            mg.  Both treatments were generally well tolerated, with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90461 -            comparable safety profiles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90462 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90463 -               [On 140430 0900 letter to VA notifies some minor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90464 -               dizziness has begun while taking Atorvastatin 10mg with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90465 -               Ezetimibe 10mg. ref SDS 57 PU43                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90467 -                ..
B90468 -               [below on 131125 0005 research finds ezetimibe (zetia)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90469 -               for secondary drug recommended by "expert" to treat high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90470 -               risk CAD patient, ref SDS 0 XG4N, where LDL-P is high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90471 -               and discordant with low LDL-C, approximated by TG/HDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90472 -               ratio < 2, ref SDS 0 QS9F, which is shown by evidence in
B90473 -               this case from lab on 131015 0724. ref SDS 38 BE6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90475 -             ..
B90476 -            In conclusion, adding ezetimibe to atorvastatin 10 mg                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90477 -            produced significantly greater favorable changes in most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90478 -            lipids at 6 and 12 weeks and significantly greater                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90479 -            attainment of prespecified LDL cholesterol levels than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90480 -            doubling or quadrupling the atorvastatin dose in patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90481 -            >=65 years old at high risk for coronary heart disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90483 -                ..
B90484 -               [On 120101 0900 received prescription for Ezetimibe, so                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90485 -               begin trial Atorvastatin 10 mg and Ezetimite 10 mg to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90486 -               manage cholesterol. ref SDS 15 6A6H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
B90488 -                ..
B90489 -               [On 140203 1147 blood test at Labcorp 2 days earlier on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90490 -               140201- lab report shows LDL-P 861 and LDL-C 81, TG 68,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90491 -               HDL 61 - best lab ever. ref SDS 54 IM3N  Lab at VA shows                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90492 -               better results with TG 47 HDL 58 computes to LDL-P 626.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90493 -               ref SDS 54 4Z66  Results achieved hiking 933 miles since                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90494 -               131015, weight dropped to 165, low-carb diet with orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90495 -               juice and Chia seeds, and taking Atorvastatin 40 mg 4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90496 -               weeks, then Atorvastatin 10 mg + Ezetimibe 10 mg 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90497 -               for total Atorvastatin 1840 mg and Ezetimibe 330 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90498 -               ref SDS 54 I17G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90499 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90500 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90502 -  ..
B90503 - Another article shows...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90504 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90505 -        AHA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
B90506 -        American Heart Association                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90507 -        Circulation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90508 -        2003; 107: 2409-2415                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90509 -        Published online before print April 28, 2003,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90510 -        doi: 10.1161/?01.CIR.0000068312.21969.C8                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90512 -         ..
B90513 -        Received December 23, 2002; revision received February 20,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90514 -        2003; accepted March 5, 2003.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90516 -         ..
B90517 -        Clinical Investigation and Reports                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
B90518 -        Effect of Ezetimibe Coadministered With Atorvastatin in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90519 -        628 Patients With Primary Hypercholesterolemia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90520 -        
B90521 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90522 -        A Prospective, Randomized, Double-Blind Trial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90523 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90524 -        https://circ.ahajournals.org/content/107/19/2409.full                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90526 -         ..
B90527 -        Christie M. Ballantyne, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90528 -        John Houri, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90529 -        Alberto Notarbartolo, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90530 -        Lorenzo Melani, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
B90531 -        Leslie J. Lipka, MD, PhD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90532 -        Ramachandran Suresh, PhD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90533 -        Steven Sun, PhD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
B90534 -        Alexandre P. LeBeaut, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90535 -        Philip T. Sager, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90536 -        Enrico P. Veltri, MD;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90537 -        for the Ezetimibe Study Group                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90539 -         ..
B90540 -        Correspondence to Christie M. Ballantyne, MD, Baylor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90541 -        College of Medicine, 6565 Fannin Street, MS A-601,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90542 -        Houston, TX 77030. E-mail cmb@bcm.tmc.edu                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90543 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90544 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90545 -        1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90546 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90547 -            1.  Background                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90549 -                Despite the established efficacy of statins, many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90550 -                patients do not achieve recommended LDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90551 -                (LDL-C) goals. Contributing factors may be inadequate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90552 -                dosing, increased risk for adverse effects with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90553 -                high-dose monotherapy, and increased potential for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90554 -                intolerance and adverse effects with combinations of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90555 -                available agents.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90556 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90558 -  ..
B90559 - Atorvastatin 10 Ezetimibe 10 HDL 5% Increase TG 30% LDL-C 50% Reduction                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90560 - HDL 5% Increase TG 30% LDL-C 50% Reduction Atorvastatin 10 Ezetimibe 10                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90561 - 
B90562 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90563 -            2.  Methods and Results                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90564 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90565 -                In a double-blind study, 628 patients with baseline                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90566 -                LDL-C 145 to 250 mg/dL and triglycerides ?350 mg/dL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90567 -                were randomly assigned to receive 1 of the following                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90568 -                for 12 weeks: ezetimibe (10 mg/d); atorvastatin (10,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90569 -                20, 40, or 80 mg/d); ezetimibe (10 mg) plus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
B90570 -                atorvastatin (10, 20, 40, or 80 mg/d); or placebo.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90571 -                primary efficacy end point was percentage reduction in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90572 -                LDL-C for pooled ezetimibe plus atorvastatin versus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90573 -                pooled atorvastatin treatment groups.  Ezetimibe plus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90574 -                atorvastatin significantly improved LDL-C, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90575 -                cholesterol (HDL-C), triglycerides, total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90576 -                cholesterol:HDL-C, and high-sensitivity C-reactive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90577 -                protein (hs-CRP) compared with atorvastatin alone                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90578 -                (P<0.01).  Coadministration of ezetimibe provided a
B90579 -                significant additional 12% LDL-C reduction, 3% HDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90580 -                increase, 8% triglyceride reduction, and 10% hs-CRP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90581 -                reduction versus atorvastatin alone.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90583 -                 ..
B90584 -                Ezetimibe plus atorvastatin provided LDL-C reductions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90585 -                of 50% to 60%, triglyceride reductions of 30% to 40%,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90586 -                and HDL-C increases of 5% to 9%, depending on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90587 -                atorvastatin dose.  LDL-C reductions with ezetimibe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90588 -                plus 10 mg atorvastatin (50%) and 80 mg atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90589 -                alone (51%) were similar.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90591 -  ..
B90592 - See "Discussion" explaining Atorvastatin 10 Ezetimibe 10 achieved 50%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90593 - redution LDL-C. ref SDS 0 MH7I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90595 -  ..
B90596 - Assume similarly, Atorvastatin 10 with Ezetimibe 10 acheved low end                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90597 - increase HDL 5%, and reduced TG 30%.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90599 -                 ..
B90600 -            3.  Conclusions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
B90601 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90602 -                Ezetimibe plus atorvastatin was well tolerated, with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90603 -                safety profile similar to atorvastatin alone and to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90604 -                placebo.  When coadministered with atorvastatin,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90605 -                ezetimibe provided significant incremental reductions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90606 -                in LDL-C and triglycerides and increases in HDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90607 -                Coadministration of ezetimibe and atorvastatin offers a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90608 -                well-tolerated and highly efficacious new treatment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90609 -                option for patients with hypercholesterolemia.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90611 -  ..
B90612 - Details of study omitted from original source...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90614 -                 ..
B90615 -            4.  Discussion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90616 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90617 -                Coadministration of ezetimibe with the starting dose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90618 -                (10 mg) of atorvastatin provided a 50% reduction in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90619 -                LDL-C, comparable to the 51% reduction obtained with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90620 -                high-dose (80 mg) atorvastatin. Because each doubling                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90621 -                of a statin dose provides only 5% to 6% additional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90622 -                LDL-C reduction,16 the need for multiple dosage                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90623 -                adjustments may limit the routine use of optimum                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90624 -                statin doses in clinical practice. Statin doses are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90625 -                often not titrated to achieve recommended LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90626 -                goals,2 and at starting doses of statin therapy, most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90627 -                patients do not receive sufficient LDL-C reductions to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90628 -                reach target.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
B90630 -                 ..
B90631 -                In ACCESS overall, at initial doses, LDL-C goals were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90632 -                met in 53% of patients receiving atorvastatin, 38% of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90633 -                patients receiving simvastatin, 28% of patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90634 -                receiving lovastatin, and 15% of patients receiving                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90635 -                pravastatin or fluvastatin.3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90637 -                 ..
B90638 -                Even fewer patients in the highest-risk category of CHD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90639 -                can achieve the ATP goal of LDL-C <100 mg/dL: 6% to 43%
B90640 -                of patients with CHD in ACCESS,3 and 1% to 32% of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
B90641 -                patients with documented atherosclerosis receiving                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90642 -                starting doses of atorvastatin, fluvastatin,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
B90643 -                lovastatin, or simvastatin.18 In ATP III, this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90644 -                highest-risk category has been expanded to include                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90645 -                individuals with noncoronary atherosclerosis, diabetes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90646 -                mellitus, and multiple risk factors conferring 10-year                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90647 -                CHD risk >20%, doubling the number of individuals with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
B90648 -                this difficult-to-attain LDL-C goal.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90650 -                 ..
B90651 -                The importance of aggressive LDL-C lowering in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90652 -                high-risk patients has been supported by the results of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
B90653 -                the Heart Protection Study,19 which showed that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90654 -                high-risk individuals with LDL-C lower than the drug                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90655 -                initiation threshold also benefited from statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
B90656 -                therapy, suggesting that the optimal LDL-C for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
B90657 -                high-risk patients may be below the goals recommended                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90658 -                by the guidelines.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90660 -                 ..
B90661 -                The significant reductions in hs-CRP observed when                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90662 -                ezetimibe was added to atorvastatin suggest an added                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90663 -                anti-inflammatory effect of the combination, possibly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90664 -                resulting from the overall complex effect of ezetimibe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90665 -                on the lipid profile. Similar reductions in hs-CRP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90666 -                were observed when ezetimibe was added to a variety of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90667 -                statins.13                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
B90669 -                 ..
B90670 -                In clinical practice, ezetimibe coadministered with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90671 -                statin may enable more patients to achieve recommended                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90672 -                target LDL-C levels by offering greater LDL-C lowering                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90673 -                with fewer dose titrations as well as a well-tolerated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90674 -                alternative for patients in whom maximal dose statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90675 -                monotherapy is inadequate.  Ezetimibe has also been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90676 -                shown to be efficacious when coadministered with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90677 -                simvastatin.  In a similarly designed study,15 the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90678 -                combination of ezetimibe (10 mg/d) and simvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90679 -                (pooled doses of 10, 20, 40, and 80 mg/d) provided                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
B90680 -                significantly greater reductions in LDL-C (13.8%) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90681 -                triglyceride (7.5%) and increases in HDL-C (2.4%) than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90682 -                simvastatin alone (P<0.01).  Combining the different
B90683 -                mechanisms of action of these agents (inhibition of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
B90684 -                cholesterol synthesis by the statin and inhibition of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90685 -                cholesterol absorption across the intestinal wall by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
B90686 -                ezetimibe) appears to provide substantial incremental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
B90687 -                reductions in LDL-C, with additional favorable changes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90688 -                in total cholesterol, triglycerides, apo B, and HDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
B90689 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90690 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90691 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90692 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90693 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90694 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90695 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90696 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B90697 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
B907 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Ezetimibe Zeita Side Effects Similar Atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
BQ03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
BQ0401 -  ..
BQ0402 - Side Effects Atorvastatin 10 MG with Ezetimibe 10 MB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0403 - Ezetimibe 10 MB Side Effects with Atorvastatin 10 MG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0404 - Side Effects Ezetimibe 10 MB with Atorvastatin 10 MG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0405 - 
BQ0406 - Atorvastatin side effects are listed in the record on 130603 0930.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
BQ0407 - ref SDS 35 PC6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0408 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0409 - Research indicates Ezetimibe has similar side effects, suggesting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
BQ0410 - compounding effect...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0411 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0412 -            Drugs.Com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
BQ0414 -             ..
BQ0415 -            Ezetimibe Side Effects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
BQ0416 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0417 -              http://www.drugs.com/sfx/ezetimibe-side-effects.html                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0419 -             ..
BQ0420 -            General Comprehensive Listing...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
BQ0421 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0422 -            1.  Abdominal fullness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
BQ0423 -            2.  Black tarry stools                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
BQ0424 -            3.  Bleeding gums                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0425 -            4.  Bloating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0426 -            5.  Blood in urine or stools                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0427 -            6.  Chills                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0428 -            7.  Constipation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
BQ0429 -            8.  Darkened urine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
BQ0430 -            9.  Fast heartbeat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
BQ0431 -           10.  Fever                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
BQ0432 -           11.  Gaseous abdominal pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0433 -           12.  General tiredness or weakness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0434 -           13.  Indigestion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
BQ0435 -           14.  Large, hive-like swelling on face, eyelids, lips,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
BQ0436 -                tongue, throat, hands, legs, feet, sex-organs                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0437 -           15.  Loss of appetite                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0438 -           16.  Light-colored stools                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
BQ0439 -           17.  Muscle cramps or spasms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0440 -           18.  Muscular tenderness, wasting or weakness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0441 -           19.  Nausea                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0442 -           20.  Pains in stomach, side or abdomen, possibly radiating to the back                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
BQ0443 -           21.  Pinpoint red spots on skin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0444 -           22.  Recurrent fever                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
BQ0445 -           23.  Severe nausea                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0446 -           24.  Skin rash                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
BQ0447 -           25.  Unusual bleeding or bruising                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
BQ0448 -           26.  Upper right abdominal pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0449 -           27.  Vomitting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
BQ0450 -           28.  Yellow eyes or skin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
BQ0452 -             ..
BQ0453 -            More Common                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0454 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0455 -            1.  Fever                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
BQ0456 -            2.  Headache                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0457 -            3.  Muscle pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
BQ0458 -            4.  Runny nose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0459 -            5.  Sore throat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
BQ0461 -             ..
BQ0462 -            Less Common                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0463 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0464 -            1.  Back pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
BQ0465 -            2.  Body aches or pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
BQ0466 -            3.  Chest pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0467 -            4.  Chills                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0468 -            5.  Cold or flu-like symptoms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
BQ0469 -            6.  Congestion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0470 -            7.  Coughing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0471 -            8.  Diarrhea                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0472 -            9.  Difficulty in moving                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
BQ0473 -           10.  Dizziness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
BQ0474 -           11.  Dryness or soreness of throat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0475 -           12.  Hoarseness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0476 -           13.  Muscle pain or stiffness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
BQ0477 -           14.  Pain in joints                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
BQ0478 -           15.  Pain or tenderness around eyes or cheekbones                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
BQ0479 -           16.  Shortness of breath or troubled breathing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
BQ0480 -           17.  Stomach pain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
BQ0481 -           18.  Stuffy nose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
BQ0482 -           19.  Tender, swollen glands in neck                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
BQ0483 -           20.  Tighness of chest or wheezing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0484 -           21.  Trouble swallowing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
BQ0485 -           22.  Unusual tiredness or weakness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0486 -           23.  Voice changes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0488 -             ..
BQ0489 -            [On 140430 0900 letter to VA notifies some minor dizziness                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
BQ0490 -            has begun while taking Atorvastatin 10mg with Ezetimibe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
BQ0491 -            10mg. ref SDS 57 PU43                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0493 -  ..
BQ0494 - Karen's letter continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0495 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0496 -        -Continue physical activity and low fat/low cholesterol diet.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
BQ0497 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0498 -        -RTC in 4 weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0499 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0500 -            [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
BQ0501 -            submits pending issues to discuss during meeting on 131219,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0502 -            ref SDS 47 8N50, and lists TG/HDL-C ratio and LDL-P issues.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
BQ0503 -            ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
BQ0505 -         ..
BQ0506 -        Patient was discussed with Dr Bikle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
BQ0508 -  ..
BQ0509 - There is a Doctor Daniel Bikle, PhD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
BQ0510 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0511 -              http://profiles.ucsf.edu/daniel.bikle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
BQ0512 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0513 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0514 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0515 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ0516 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
BQ06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Atorvastatin 10 MG 4-week Trial VA Treatment Plan Test Side Effects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
CS03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
CS04 - 1702                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
CS0501 -  ..
CS0502 - VA Confirm Work Plan Atorvastan 4-week Trial then Add Ezetimibe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
CS0503 - 
CS0504 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0505 - Received letter from Doctor Alba saying...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
CS0506 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0507 -    1.  Subject:  RE: VA Excellent Care Post CABG x4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
CS0508 -        Date:  Mon, 25 Nov 2013 23:21:49 +0000                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
CS0515 -         ..
CS0516 -    2.  I am, sorry about the confusion, I thought you had received my                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
CS0517 -        email                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
CS0519 -         ..
CS0520 -    3.  Plan is to start Atorvstatin 10 mg po daily- since you have 40                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
CS0521 -        mg pills- I already ordered the 10 mg pills, so they can be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
CS0522 -        mailed to you, unless you prefer to pick them up.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
CS0523 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0524 -            [...below on 131125 0005 at 2048 letter to Doctor Alba and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
CS0525 -            reports taking Atorvastatin 40 mg, because have not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
CS0526 -            received prescription for 10 mg dose, and leaving town for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
CS0527 -            a week. ref SDS 0 2F66                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
CS0529 -         ..
CS0530 -    4.  I did not place an order for repeat labs in 4 weeks, since that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
CS0531 -        is not enough time to see the full effect of the Atorvastatin.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
CS0533 -         ..
CS0534 -    5.  I wanted to follow up with you in 4 weeks to see if you are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
CS0535 -        tolerating the medication well, and to further discuss                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
CS0536 -        treatment plan.  Happy Holidays .                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
CS0537 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0538 -            [On 131210 received letter from Doctor Alba asking about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
CS0539 -            progress taking Atorvastatin 40 mg, and requesting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
CS0540 -            submission of pending issues for next meeting. ref SDS 46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
CS0541 -            HY6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0543 -             ..
CS0544 -            [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
CS0545 -            submits pending issues to discuss during meeting on 131219,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
CS0546 -            ref SDS 47 8N50, and lists TG/HDL-C ratio and LDL-P issues.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
CS0547 -            ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
CS0548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0553 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0554 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0555 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0556 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS0557 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
CS06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Chia Seeds Implement Recommend Manage Cholesterol Weight Energy Comm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
DE03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
DE04 - 2006                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
DE0501 -  ..
DE0502 - Letter to Karen says...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
DE0503 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0504 -    1.  Subject:  Chia Seeds - Mission Accomplished                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
DE0505 -        Date:  Mon, 25 Nov 2013 20:16:56 -0800                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
DE0512 -         ..
DE0513 -    2.  Thanks for your letter earlier today, shown above, ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
DE0514 -        7Z3N, and facilitating communication with Doctor Alba through                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
DE0515 -        her attending.  Doctor Alba responded later in the afternoon,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
DE0516 -        so we are all on the same page.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
DE0518 -         ..
DE0519 -    3.  Very grateful for your help investigating clinical trials that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
DE0520 -        avoid arteriosclerosis without using statins. [...cited in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
DE0521 -        Karen's letter earlier today, per above, ref SDS 0 V163, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
DE0522 -        following up on patient's request in the letter to the VA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
DE0523 -        earlier this morning, per above. ref SDS 0 UK59 ...].  Trials                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
DE0524 -        that might fit my patient profile were reviewed with Doctor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
DE0525 -        Egan during the meeting on 131017. ref SDS 40 179N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0527 -         ..
DE0528 -    4.  See in particular Alirocumab showing promising results, cited                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
DE0529 -        in the record on line 600467.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
DE0531 -         ..
DE0532 -    5.  Today, implemented your suggestion to try Chia seeds.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
DE0533 -        check out lady at Costco, said, "Oh, Chia seeds!  They're                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
DE0534 -        great." That's the first time the check out lady has ever                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
DE0535 -        commented on my groceries.  Anyway, put some in regular dish                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
DE0536 -        this evening, shown in case study on 120101 line 099395.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0537 -        ref SDS 15 746M                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
DE0539 -  ..
DE0540 - Karen suggested trying Chia seeds, during the meeting at the VA on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
DE0541 - 131121 0930. ref SDS 44 NQ37                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
DE0543 -  ..
DE0544 - Research on Chia seeds indicates it helps control cholesterol and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
DE0545 - weight, and it increases energy. ref SDS 44 HK5J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
DE0547 -  ..
DE0548 - Letter to Karen continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
DE0549 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0550 -    6.  Didn't notice any change in taste, so Chia seeds seem benign.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
DE0551 -        Thanks for the tip.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
DE0552 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0558 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0559 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE0560 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
DE07 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
DE0701 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
DE08 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Notify VA Implement Prescription Atorvastatin 10 MG 4-week Trial VA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
EN03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
EN04 - 2048                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
EN0501 -  ..
EN0502 - Notify Doctor Alba Implement Prescription Atorvastatin Manage Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
EN0503 - 
EN0504 - Letter submitted to Doctor Alba saying...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
EN0505 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0506 -    1.  Subject:  VA Meeting 21 Nov 2013, Clinical Trials Non-statin Solutions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
EN0507 -        Date:  Mon, 25 Nov 2013 21:14:45 -0800                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
EN0514 -         ..
EN0515 -    2.  Thanks for your letter this afternoon, shown above, ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
EN0516 -        I67O, confirming understandings meeting at the VA this past                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
EN0517 -        Thursday on 131121.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
EN0519 -         ..
EN0520 -    3.  I'm leaving tonight for a week.  Have not yet received your new                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
EN0521 -        prescription Atorvastatin 10 MG.  As you noticed in patient                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
EN0522 -        history, Atorvastatin 40 MG was started on 131121. [...shown in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
EN0523 -        case study on 120101 0900. ref SDS 15 RN3F...].                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
EN0525 -         ..
EN0526 -    4.  40 mg pills are on hand from Doctor Egan's prescription in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
EN0527 -        June, which was not implemented to avoid statin side effects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
EN0529 -         ..
EN0530 -    5.  Research further indicates good results adding Zetia to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
EN0531 -        Atvorstatin 10 mg. [...shown in the record today, above.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0532 -        ref SDS 0 WL7I...].  While my goal is to avoid statins, it's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
EN0533 -        great that the VA and UCSF may have this solution available to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
EN0534 -        try in 4 weeks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
EN0536 -         ..
EN0537 -    6.  Some background on clinical trials to lower cholesterol without                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
EN0538 -        statin drugs is shown in the record last month on 131017.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
EN0539 -        ref SDS 40 179N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
EN0541 -         ..
EN0542 -    7.  See in particular Alirocumab showing promising results for a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
EN0543 -        non-statin, cited in the record on line 600467.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
EN0545 -         ..
EN0546 -    8.  Very grateful for your support.  Looking forward to meeting in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
EN0547 -        4 weeks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0549 -            [On 131210 received letter from Doctor Alba asking about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
EN0550 -            progress taking Atorvastatin 40 mg, and requesting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
EN0551 -            submission of pending issues for next meeting. ref SDS 46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
EN0552 -            HY6O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0554 -             ..
EN0555 -            [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
EN0556 -            submits pending issues to discuss during meeting on 131219,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
EN0557 -            ref SDS 47 8N50, and lists TG/HDL-C ratio and LDL-P issues.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
EN0558 -            ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
EN0559 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0565 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0566 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN0567 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
EN06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
LDL < 70 Not Effective Goal Avoid Arterialsclorosis CVD CAD Manage C   E6
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
FG03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
FG0401 -  ..
FG0402 - Research Arterialsclorsis Cornorary Artery Disease and Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0403 - High LDL-C Low LDL-P Discordance Lowers Risk Shown by TG HDL-C Ratio 2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0404 - 
FG0405 - Follow up ref SDS 2 P95F.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0407 - Cholesterol was reviewed previously caring for Millie, reported on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0408 - 081226 0930. ref SDS 2 HK8O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0410 -  ..
FG0411 - Found writing on the Internet....                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0412 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0413 -    1.  Tim Russert's Fatal Heart Attack Was Preventable, He Followed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0414 -        Antiquated Advice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
FG0416 -         ..
FG0417 -        Date............................. no date                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0418 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0419 -              http://livinlavidalowcarb.com/blog/tim-russerts-fatal-heart-attack-was-preventable-he-followed-antiquated-advice/2403                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0420 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0421 -        1.  In this supercharged and oftentimes volatile political                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0422 -            election year, something tragic and sudden struck this country                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
FG0423 -            and has everyone buzzing in Washington and across the United                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0424 -            States. No, it wasn't some sex scandal, drug bust, or any of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0425 -            the other usual news that has become almost too commonplace                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0426 -            these days. This was something much more serious and has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0427 -            greater implications than even the extensive coverage the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0428 -            mainstream media is giving to it.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
FG0430 -             ..
FG0431 -        2.  Last Friday afternoon, hard-hitting political interviewer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0432 -            and long-time host of NBC-TV's Sunday morning news talk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0433 -            show "Meet the Press", Tim Russert, experienced his first                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0434 -            heart attack and it almost instantly killed him.  I cannot                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0435 -            imagine how his family is responding to this news and my                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0436 -            sympathies and prayers go out to them during this very                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0437 -            difficult time.  Tim was in the midst of doing what he                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0438 -            loved - preparing for his television show - when the heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0439 -            attack took his life and took him away from all of us.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0441 -             ..
FG0442 -        3.  So, how did a 58-year old man die from a heart attack when                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0443 -            he was doing all of the things his doctor said he should to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0444 -            prevent it?  Should we be concerned about what doctors are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0445 -            telling us about how to ward off cardiovascular disease so                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0446 -            that we don?t become the next victim of what befell Tim                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0447 -            Russert? These are the questions people are asking in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0448 -            wake of this tragedy and was the subject of what one of my                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0449 -            readers wanted to know in an e-mail I received.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
FG0451 -             ..
FG0452 -        4.  Here's what she wrote:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0453 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0454 -                Hi Jimmy, I have been an avid reader of your blog for a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0455 -                long time.  I am so scared since Tim Russert died                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0456 -                suddenly of a heart attack at only age 58 (my husband                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0457 -                is 57 and I?m 54) that I'd really like to get some                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0458 -                clarification on the statin drugs and cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0459 -                issue.  Seems like Tim Russert's doctors did all the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0460 -                usual things and he died anyway.  I trust what Dr Jonny                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0461 -                Bowden has to say as he has an advanced degree in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0462 -                nutrition and he seems to think for himself instead of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0463 -                just following the status quo.  Can you see if he would                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0464 -                help reassure me with this?  Thanks for your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
FG0465 -                assistance, and keep up the fantastic work!                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
FG0467 -             ..
FG0468 -        5.  While I am no Dr Jonny Bowden, I do have some things to say                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0469 -            about Tim Russert's death that need to be said.  I can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0470 -            understand your concerns and I am delighted to forward your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0471 -            questions to Dr Jonny Bowden.  He's one of the brightest,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0472 -            most articulate people on nutrition in the entire world, so                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0473 -            you are in good hands with the information he provides to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0474 -            you.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0476 -             ..
FG0477 -        6.  But if you would allow me to comment on this subject, I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0478 -            have some thoughts about it.  Isn't it interesting that Tim                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0479 -            Russert did everything exactly as his doctor wanted him to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0480 -            and yet his very first heart attack was a fatal one?  I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0481 -            don?t think that?s a coincidence either and it happens                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0482 -            every single day without a blink of an eye from anyone.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0484 -             ..
FG0485 -        7.  Watch this video interview with Russert's doctor to see how                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0486 -            dejected he is about Russert's "unexpected" death despite his                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
FG0487 -            best treatment strategies. It's amazing to hear his doctor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0488 -            basically say that Tim did everything he was "supposed" to do                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
FG0489 -            and yet it wasn't enough to save his life. Wanna know what the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
FG0490 -            scariest part of this story is?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
FG0491 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0493 -  ..
FG0494 - Exercise Russert Overweight Died Low HDL High TG Despite LDL < 70
FG0495 - Russert Died Low HDL and High TG Several Years Excess Weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
FG0496 - Triglycerides High HDL Low Russert Died CVD with Low LDL Excess Weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0497 - HDL Low Triglycerides High Russert Died CVD with Low LDL Excess Weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0498 - 
FG0499 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0500 -        8.  Check out Tim Russert's lipid profile:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0501 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0502 -            LDL-68                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0503 -            HDL-37 (up from the lower 20's)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
FG0504 -            Total Cholesterol-105                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0506 -             ..
FG0507 -        9.  Did you see that?  Most doctors would look at those numbers                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0508 -            and say, "See how healthy this person is because we lowered                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0509 -            his cholesterol." And they would pound their chest with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0510 -            pride at putting someone like Tim Russert on a statin drug                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0511 -            to artificially make this happen.  But what good did it do                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0512 -            him in the end?  He's gone now because of that advice and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0513 -            there's no outrage about it.  Worry, concern, perplexity,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0514 -            yes - but nobody is angry that this preventable death was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0515 -            made WORSE by the use of all the traditional means for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
FG0516 -            improving heart health.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0518 -             ..
FG0519 -       10.  According to Russert's doctor, he didn't have Type 2 diabetes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
FG0520 -            nor did he have any blood sugar issues at all. His A1c was in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
FG0521 -            the normal range and as I noted previously his cholesterol was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
FG0522 -            considered VERY healthy. For all intents and purposes according                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
FG0523 -            to the modern day medical conventional wisdom, he was the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0524 -            epitome of perfect health. And yet he tragically died before                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0525 -            his time.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0527 -             ..
FG0528 -       11.  We now know posthumously that Russert had coronary heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0529 -            disease that he was being treated for, but his doctor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0530 -            apparently didn't know how severe it was.  But even if he                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0531 -            did know it was extremely serious, what else would he have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0532 -            recommended to Tim?  Higher doses of his statin drug?  Even                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0533 -            less fat in his diet?  More exercise?  In the end, all of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0534 -            these seemingly good strategies from the conventional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0535 -            wisdom point of view would have very likely done NOTHING to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0536 -            prevent this from happening.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
FG0538 -  ..
FG0539 - Exercise Bike Failed Russert Overweight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
FG0540 - 
FG0541 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0542 -       12.  His doctor put him on blood pressure lowering medication as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0543 -            well as a cholesterol-lowering statin drug to see if that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0544 -            would help. And Russert even rode an exercise bike to try                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0545 -            to lose weight, although it didn't work.  There's no doubt                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0546 -            the plaque buildup around his heart was getting bigger and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0547 -            bigger over the years until his heart couldn't take it any                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0548 -            longer.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
FG0550 -  ..
FG0551 - This record indicates that merely "exercising" is not sufficient for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0552 - cardiovasular health, unless eating food is reduced and exercise is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0553 - balanced sufficiently to avoid being overweight.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
FG0555 -  ..
FG0556 - The problem is more urgent for insulin resistant people with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
FG0557 - diabetes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
FG0558 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0560 -  ..
FG0561 - Article Tim Russert's Fatal Heart Attack Preventable continued...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0562 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0563 -       13.  We know that too low LDL can lead to depression, suicide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
FG0564 -            and death.  We also know that HDL "good" cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0565 -            (Russert's was very low-NOT good) and triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
FG0566 -            (something Russert dealt with having too high over the past                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0567 -            few years) are better indicators of heart health than LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
FG0568 -            and total cholesterol.  And it's a high-carb, low-fat diet                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
FG0569 -            that leads to lower HDL and higher triglycerides.  No doubt                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0570 -            this is precisely the kind of diet Russert?s doctor had him                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
FG0571 -            on.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
FG0572 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0573 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0574 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG0575 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
FG06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Cholesterol Research Internet Low Carbohydrate Diet Lower Triglyceri                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
GL03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
GL0401 -  ..
GL0402 - Low-Carb Diet Lower Triglycerides Large LDL Particle Size Protective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0403 - LDL 246 Cholesterol 326 Healthy with TG 77 HDL 65                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
GL0404 - LDL-P Size Large Fluffy Protective with HDL 65 and TG 77                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0405 - Protective LDL Particle Large Size Fluffy with HDL 65 and TG 77                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
GL0406 - 
GL0407 - Author reports personal lipid profile similar to lab on 131015 0724.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0408 - ref SDS 38 IM9N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0410 -       14.  As you know from reading my blog, my most recent total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
GL0411 -            cholesterol reading was 326 with an LDL of 246, HDL of 65,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0412 -            and triglycerides at 77.  I am confident I don't need to go                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0413 -            on a statin drug now or ever and I am as healthy as I have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0414 -            ever been in my entire life.  On face value, any typical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
GL0415 -            physician in America would say to me, "Oh my God, you need                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0416 -            to be on Lipitor, Crestor, or Zetia to lower your LDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0417 -            total cholesterol."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
GL0419 -             ..
GL0420 -       15.  Of course, they would be 100% wrong because my LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0421 -            size is the protective large, fluffy kind that your body                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
GL0422 -            wants and needs.  Dr Eric Westman from Duke University                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
GL0423 -            Medical Center in Durham, North Carolina, who is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0424 -            physician who ran this test on my behalf, said almost all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0425 -            of my LDL is this protective kind and the percentage of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
GL0426 -            small, dense LDL (which was the likely culprit in Russert's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0427 -            fatal heart attack) is virtually nil.  And that's a GREAT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0428 -            thing!  High LDL can be good, but low HDL is most certainly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0429 -            ALWAYS a bad thing to have.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0430 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0431 -               [...below on 131125 0005 this article Doctor Sigurdsson                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0432 -               explains discordant lab results for LDL-C high and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
GL0433 -               LDL-particle low is healthy profile, because LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
GL0434 -               particles are large with high concentration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
GL0435 -               cholesterol that cannot penetrate the endothelial layer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0436 -               lining artery walls, and so prevents arterialsclorosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0437 -               ref SDS 0 M95O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
GL0439 -                ..
GL0440 -               [...below on 131125 0005 this article Doctor Sigurdsson                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0441 -               further reports patients with small-dense LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0442 -               have 3-fold increase risk of CVD than patients with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
GL0443 -               large-fluffy LDL particles, which is protective against                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0444 -               CVD. ref SDS 0 N044                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
GL0446 -                ..
GL0447 -               [...below on 131125 0005 this article Doctor Attia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0448 -               explains discordant lab results for LDL-C high and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
GL0449 -               LDL-particle low is healthy profile, because LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
GL0450 -               particles are large with high concentration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
GL0451 -               cholesterol that cannot penetrate the endothelial layer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0452 -               lining artery walls, and so prevents arterialsclorosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0453 -               ref SDS 0 FM6L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
GL0455 -                ..
GL0456 -               [...below on 131125 0005 another article presents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
GL0457 -               diagrams of small LDL particles with high concentration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0458 -               of triglycerides and depleted cholesterol, and comparing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0459 -               with large LDL particles with low concentrations of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
GL0460 -               triglycerides and high concentration of cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
GL0461 -               sometimes described as "fluffy" LDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
GL0462 -               ref SDS 0 1V4J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
GL0463 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0464 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0466 -  ..
GL0467 - Low Carb Diet TG/HDL Ratio < 2 Lower Risk Arterialsclorosis CVD
GL0468 - TG/HDL Ratio < 2 Low Carb Diet Lower Risk Arterialsclorosis CVD
GL0469 - Ratio TG/HDL < 2 Low Carb Diet Lower Risk Arterialsclorosis CVD
GL0470 - 
GL0471 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0472 -       16.  When you are livin' la vida low-carb correctly, then your HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
GL0473 -            will be well above 50 and for women well above 70. At the same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0474 -            time, your triglycerides will drop below 100 for an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
GL0475 -            HDL/triglyceride ratio of around 1. That's what you want.  Of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
GL0476 -            course, you will need to get the particle size of your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
GL0477 -            cholesterol subsets measured using a VAP or Berkeley test, but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0478 -            you can almost be guaranteed that if your HDL is up over 50 and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
GL0479 -            your triglycerides are down below 100 that your LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
GL0480 -            size will be the large, fluffy protective kind.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
GL0481 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0482 -                [...below on 131125 0005 article "Doc's Opinion" by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0483 -                Doctor Axel F Sigurdsson recommends low-carb diet for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0484 -                lowering LDL-P. ref SDS 0 QP9F and ref SDS 0 J56H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
GL0486 -                 ..
GL0487 -                [...below on 131125 0005 article "Doc's Opinion" by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
GL0488 -                Doctor Axel F Sigurdsson cites TG/HDL ratio > 2 signals                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0489 -                high risk arterialsclorosis and CVD. ref SDS 0 666G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
GL0491 -                 ..
GL0492 -                [...below on 131125 0005 review of article by Doctor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
GL0493 -                Attia, seems to support reliance on TG/HDL-C ratio to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
GL0494 -                approximate results of LDL-P testing. ref SDS 0 338N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
GL0496 -                 ..
GL0497 -                [...below on 131125 0005 abstract article published by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0498 -                Pub Med.gov combined parameter, the TG/HDL-C ratio, is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
GL0499 -                beneficial for assessing the presence of small LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
GL0500 -                ref SDS 0 VR5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
GL0502 -                 ..
GL0503 -                [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0504 -                submits pending issues to discuss during meeting on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
GL0505 -                131219, ref SDS 47 8N50, and lists TG/HDL-C ratio and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
GL0506 -                LDL-P test issues. ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
GL0508 -                 ..
GL0509 -                [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
GL0510 -                LDL-P at Labcor on Health Testing Centers order #                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
GL0511 -                27716. ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
GL0512 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0513 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0514 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL0515 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
GL06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Doc's Opinion Axel F Sigurdsson Research Internet Arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
HD03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
HD0401 -  ..
HD0402 - Cholesterol Bound Atherogenic Lipoproteins Causes Aterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
HD0403 - 
HD0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0405 - Another article says...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
HD0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0407 -    2.  Doc's Opinion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0408 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0409 -            Doc's opinion is written and edited by Axel F Sigurdsson                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
HD0410 -            MD, PhD, FACC.  Dr Sigurdsson is a cardiologist at the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0411 -            Department of Cardiology at the Landspitali University                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0412 -            Hospital in Reykjavik Iceland.  He also practices                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
HD0413 -            cardiology at Hjartamidstodin (The Heart Center) which is a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
HD0414 -            private heart clinic in the Reykjavik area.  He is a Fellow                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
HD0415 -            of the American College of Cardiology (ACC), The Icelandic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0416 -            Society of Cardiology and the Swedish Society of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
HD0417 -            Cardiology.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
HD0419 -         ..
HD0420 -        Date............................. 21 November 2012                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
HD0421 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0422 -              http://www.docsopinion.com/2012/11/21/the-difference-between-ldl-c-and-ldl-p/                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
HD0424 -             ..
HD0425 -        1.  The lipid hypothesis, suggesting a causative role for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
HD0426 -            cholesterol in atherosclerotic heart disease is by many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
HD0427 -            considered one of the best proven hypotheses in modern                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0428 -            medicine.  Measurements of total cholesterol, and the magnitude                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
HD0429 -            of cholesterol bound to different lipoproteins, are commonly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0430 -            used to assess the risk of future cardiovascular events.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
HD0431 -            However, recent research into the role of lipoproteins in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0432 -            atherosclerosis, the role of oxidation and inflammation, has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0433 -            indicated that cholesterol in itself does not cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
HD0434 -            atherosclerosis.  It is only when cholesterol bound to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0435 -            atherogenic lipoproteins becomes trapped within the arterial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0436 -            wall, that it becomes a part of the atherosclerotic process.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0437 -            Certainly, atherosclerosis as we know it will not occur in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
HD0438 -            absence of cholesterol.  Thus, cholesterol is definitively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0439 -            involved, and necessary for  atherosclerosis to occur, but so                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
HD0440 -            are many other important organic molecules that play a role in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
HD0441 -            health and disease.  The necessity of cholesterol does not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0442 -            prove its causative role.  So, in order to understand the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0443 -            pathophysiology of atherosclerosis and the role of lipoproteins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
HD0444 -            and inflammation, we may have to loosen our grip on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
HD0445 -            cholesterol, at least for the time being.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0447 -             ..
HD0448 -        2.  Lipoproteins and atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
HD0449 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0450 -            The insolubility of lipids in water poses a problem because                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
HD0451 -            lipids must be transported through aqueous compartments                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
HD0452 -            within the cell as well as in the blood and tissue spaces.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0453 -            Lipoproteins are biochemical structures that enable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
HD0454 -            transport of lipids throughout the body.  A lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
HD0455 -            includes a core, consisting of a droplet of triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0456 -            and/or cholesterlyl esters, a surface layer of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
HD0457 -            phospholipid, unesterified cholesterol and specific                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
HD0458 -            proteins (apolipoproteins).  Lipoprotein particles are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0459 -            commonly classified according to their density, thus the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
HD0460 -            terms high density lipoprotein (HDL) and low density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0461 -            lipoprotein (LDL).  Apolipoprotein B (apoB) is the primary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0462 -            lipoprotein in LDL.  ApoB containing lipoproteins play a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
HD0463 -            hugely important role in atherosclerosis.  In                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
HD0464 -            atherosclerosis aplipoprotein containing lipoproteins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
HD0465 -            become trapped within the arterial wall, even when blood                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
HD0466 -            levels of cholesterol are normal.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
HD0468 -             ..
HD0469 -        3.  Atherosclerosis is a complex process.  Initially, LDL and other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
HD0470 -            apoB containing lipoproteins enter the arterial wall.  Why this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
HD0471 -            happens and why lipoproteins are retained in the wall of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0472 -            artery is still not completely clear.  Chemical substances                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0473 -            called proteoglycans play an important role for the retention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
HD0474 -            of apoB containing lipoproteins within the arterial wall.  This                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
HD0475 -            chemical intrusion then appears to initiate a maladaptive and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
HD0476 -            chronic inflammatory response leading to the formation of an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0477 -            atherosclerotic plaque.  Such plaques may cause narrowing of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
HD0478 -            important vessels such as the coronary arteries.  A rupture of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
HD0479 -            such a plaque with subsequent thrombosis may lead to an acute                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
HD0480 -            occlusion of a coronary artery causing an acute myocardial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0481 -            infarction.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
HD0483 -             ..
HD0484 -        4.  The difference between LDL-C and LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0485 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0486 -            In the clinical world, an important question is how we can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0487 -            use laboratory measurements to assess individual risk.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
HD0488 -            Calculated, or less frequently measured low density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
HD0489 -            lipoprotein cholesterol (LDL-C ) is the most commonly used                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0490 -            marker to assess risk.  LDL-C is also used to target                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0491 -            therapy in primary as well as secondary prevention of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
HD0492 -            cardiovascular disease.  This is partly due to the fact                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
HD0493 -            that most of the cholesterol in the blood is carried in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
HD0494 -            LDL's.  Moreover, there appears to be a strong and graded                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0495 -            association between LDL-C and the risk for cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
HD0496 -            disease.  However, LDL-levels may not be correctly assessed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
HD0497 -            by the measurements of cholesterol carried within these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
HD0498 -            particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
HD0499 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0500 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD0501 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
HD06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Doc's Opinion Axel F Sigurdsson Research Internet Arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I603 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
I60401 -  ..
I60402 - Triglycerides Indicate Small LDL Particle Size High Risk CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
I60403 - High LDL Particle Count Indicates Cholesterol Depleted LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
I60404 - Artiarialsclorosis Caused by High Number LDL Particles LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
I60405 - Cholesterol in LDL Particles Not Causative Artialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
I60406 - 
I60407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60408 -        5.  Let me explain this a little bit further.  LDL-C is a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60409 -            measurement of the cholesterol mass within LDL-particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60410 -            Due to the fact that LDL-C has been traditionally used for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60411 -            so many years to reflect the amount of LDL, LDL-C and LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60412 -            have become almost synonymous.  This may be quite                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
I60413 -            misleading, because the cholesterol content of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
I60414 -            particles varies greatly.  Thus, LDL-C is a surrogate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60415 -            measure that only provides an estimate of LDL levels.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60416 -            Studies indicate that the risk for atherosclerosis is more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60417 -            related to the number of LDL particles (LDL-P) than the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60418 -            total amount of cholesterol within these particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
I60420 -             ..
I60421 -        6.  It is also important to remember that LDL particles carry                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60422 -            other molecules than cholesterol.  For example,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60423 -            triglycerides (TG) are also carried within LDL-particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60424 -            Similar to total cholesterol and LDL-C, there is an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
I60425 -            association between serum TG and the risk of cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60426 -            disease.  TG molecules are larger than cholesterol ester                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60427 -            molecules.  If the number of TG molecules in an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60428 -            LDL-particle is high, there will be less space for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
I60429 -            cholesterol molecules. Therefore, if triglycerides are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60430 -            high, it may take many more LDL particles to carry a given                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60431 -            amount of cholesterol.  Therefore high LDL particle count                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60432 -            may be associated with small, cholesterol depleted,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
I60433 -            triglyceride rich particles.  Research has shown that high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60434 -            levels of triglycerides are associated with small LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60435 -            particle size.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
I60436 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60437 -               [...below on 131125 0005 article by Doctor Attia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60438 -               maintains arterialsclerosis plaque caused by cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60439 -               depleted and triglyceride rich LDL particles that are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60440 -               small and dense enough to penetrate endothelial layer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60441 -               lining arterial wall. ref SDS 0 JT6K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60443 -                ..
I60444 -               [...below on 131125 0005 report on study in 2007,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60445 -               maintains arterialsclerosis plaque caused by cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60446 -               rich LDL particles within the arterial wall. ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60447 -               UU8M                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60449 -             ..
I60450 -        7.  Now, what does all this mean? It means that one person                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60451 -            (person A) may have large cholesterol rich LDL particles,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60452 -            while another (person B) may have smaller cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60453 -            depleted particles.  These two persons may have the same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60454 -            LDL-C concentration.  However, person B will have higher                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60455 -            LDL particle number (LDL-P).  Despite similar levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60456 -            LDL-C, person B is at higher risk for future cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60457 -            events.  Furthermore, person B will have more small                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
I60458 -            LDL-particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
I60459 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60460 -               [...below on 131125 0005 this article Doctor Attia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60461 -               further explains discordant lab results for LDL-C high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60462 -               and LDL-particle low is healthy profile, because LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60463 -               particles are large with high concentration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
I60464 -               cholesterol that cannot penetrate the endothelial layer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60465 -               lining artery walls, and so prevents arterialsclorosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60466 -               ref SDS 0 FM6L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
I60468 -                ..
I60469 -               [...below on 131125 0005 another article presents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60470 -               diagrams of small LDL particles with high concentration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60471 -               of triglycerides and depleted cholesterol, and comparing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60472 -               with large LDL particles with low concentrations of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60473 -               triglycerides and high concentration of cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60474 -               sometimes described as "fluffy" LDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
I60475 -               ref SDS 0 1V4J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
I60476 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60478 -  ..
I60479 - LDL-C Low May Indicate High Risk CVD Arterialsclorsis Discordance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60480 - Discordance Low LDL-C May Indicate High Risk CVD Arterialsclorsis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60481 - ApoB LDL-P Both Predict Risk CVD Arterialsclorsis Better than LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60482 - LDL-P Size Small 300% Greater Risk CVD Large LDL-P Cholesterol Protective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60483 - 
I60484 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60485 - Large Fluffy LDL Particles Protective 300% Lower Risk than Small Dense LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
I60486 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60487 -        8.  Some studies have suggested that the size of LDL-particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60488 -            may be of importance.  People whose LDL particles are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60489 -            predominantly small and dense, have a threefold greater                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60490 -            risk of coronary heart disease.  Furthermore, the large and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60491 -            fluffy type of LDL may actually be protective.  However, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60492 -            is possible that the association between small LDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60493 -            heart disease reflects an increased number of LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60494 -            in patients with small LDL.  Therefore, the LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60495 -            count could be more important in terms of risk than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
I60496 -            particle size in itself.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60498 -                ..
I60499 -               [...above on 131125 0005 line - Doctor Attia's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60500 -               explanation here of cholesterol-depleted and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60501 -               triglyceride-rich LDL particles indicates large number                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60502 -               of "small-size" LDL particles that present much higher                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60503 -               risk of penetrating endothelial layer lining arteries to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60504 -               cause arterialsclorosis and CVD, and that LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60505 -               that are "large-fluffy" cholesterol-rich and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60506 -               triglyceride depleted lower risk of CVD - aligns with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60507 -               explanation above. ref SDS 0 6P4N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60509 -                ..
I60510 -               [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
I60511 -               LDL-P at Labcor on Health Testing Centers order # 27716.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60512 -               ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60514 -             ..
I60515 -        9.  ApoB and LDL-P both reflect the number of atherogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60516 -            lipoprotein particles.  Measurements of ApoB and LDL-P are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60517 -            better predictors of cardiovascular disease risk than LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
I60518 -            Furthermore, ApoB and LDL-P may predict residual risk among                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60519 -            individuals who have had their LDL-C levels lowered by statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
I60520 -            therapy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
I60522 -             ..
I60523 -       10.  Discordance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60524 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60525 -            Discordance is when there is a difference between LDL-C and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60526 -            LDL-P.  If LDL-C is high and LDL-P is low, there is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
I60527 -            discordance.  If LDL-C is low and LDL-P is high, there is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60528 -            discordance.  If both are low or both high, there is no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60529 -            discordance.  Studies have indicated that if there is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60530 -            discordance between LDL-C and LDL-P, cardiovascular disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60531 -            risk tracks more closely with LDL-P than LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60532 -            Specifically, when a patient with low LDL-C has a level of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60533 -            LDL-P that is not equally low, there is higher "residual"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
I60534 -            risk.  This may help explain the high number of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
I60535 -            cardiovascular events that occur in patients with normal or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60536 -            low levels of LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60538 -             ..
I60539 -       11.  An analysis of "Get With the Guidelines" data published in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
I60540 -            2009 studied almost 137 thousand patients with an acute                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
I60541 -            coronary event. Almost half of those had admission LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60542 -            levels <100 mg/dL (2.6 mmol/L).  Thus, LDL-C does not seem
I60543 -            to be predicting risk in these patients.  However, low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60544 -            HDL-C and elevated TG was common among these patients.  Low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
I60545 -            HDL-C and high TG is generally associated with higher                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
I60546 -            LDL-P.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
I60547 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I60549 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
I606 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Doc's Opinion Axel F Sigurdsson Research Internet Metabolic Syndrome                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
J003 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
J00401 -  ..
J00402 - Lipid Panal ApoB LDL-P Assess CVD Risk Better than LDL-C Misleading                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
J00403 - CVD Risk High LDL-P High and LDL-C Low Metabolic Syndrome Means Overweight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
J00404 - LDL-P High and LDL-C Low High Risk CVD Metabolic Syndrome Means Overweight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
J00405 - Metabolic Syndrome Means Overweight LDL-P High and LDL-C Low High Risk CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
J00406 - 
J00407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00408 -       12.  Among discordant patients in the Framingham Offspring Study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
J00409 -            the group with the highest risk for future cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
J00410 -            events had high LDL-P and low LDL-C, while the group with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
J00411 -            the lowest risk had low LDL-P but higher LDL-C.  Many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
J00412 -            patients with the metabolic syndrome or type-2 diabetes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
J00413 -            have the type of discordance where LDL-P is elevated but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
J00414 -            LDL-C may be close to normal.  In these individuals,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00415 -            measurements of LDL-C may underestimate cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
J00416 -            risk.  Measurements of ApoB or LDL-P may therefore be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
J00417 -            helpful in these individuals.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
J00418 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00419 -               [On 150526 1300 Doctor Stewart at VA MCSF recommended                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
J00420 -               book "Fat Chance" for managing metabolic syndrome toward                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
J00421 -               better health; book was criticized for lack of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
J00422 -               scientific founding, and presenting unrealistic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
J00423 -               remedies. ref SDS 68 ZA9O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
J00425 -             ..
J00426 -       13.  Discordance may be an important clinical phenomenon.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00427 -            Sometimes the question of medical therapy in primary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00428 -            prevention arises when there is intermediate risk, based on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
J00429 -            LDL-C.  In these cases a low LDL-P level might help to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
J00430 -            confirm that the risk is indeed low, which might justify                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
J00431 -            avoiding statin therapy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
J00432 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00433 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J00434 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
J005 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Doc's Opinion Axel F Sigurdsson Research Internet Arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
K103 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
K10401 -  ..
K10402 - LDL-C Lower Statins Misleading Don't Lower LDL-P ApoB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
K10403 - Statin Medication Lowers LDL-C More than LDL-P Misleading                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
K10404 - 
K10405 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10406 -       14.  Statins tend to lower LDL-C more than LDL-P.  Many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
K10407 -            individuals who reach the target for LDL-C with statins,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
K10408 -            may still have raised LDL-P.  This may indicate residual                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
K10409 -            risk despite what is generally defined as adequate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
K10410 -            treatment.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
K10412 -             ..
K10413 -       15.  Effect of therapies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
K10414 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10415 -            In general, most methods that lower LDL-C have some ability                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
K10416 -            to lower LDL-P.  However, there are some differences.  Much                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
K10417 -            has been written about how to lower LDL-C.  Most doctors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
K10418 -            will recommend eating less fat and cholesterol from meat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
K10419 -            and dairy products.  Statin therapy significantly lowers                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
K10420 -            LDL-C.  Therapies may affect LDL-P differently.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
K10421 -            Interventions that will lower LDL-C more than LDL-P include                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
K10422 -            statins, estrogen replacement therapy, some                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
K10423 -            antiretrovirals, and a low-fat, high-carbohydrate diet.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
K10425 -  ..
K10426 - This analysis reflects explanation of discordance, above. ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
K10427 - E36J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
K10428 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10429 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10430 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10431 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10432 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K10433 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
K105 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Eating Academy Peter Attia MD Research Internet Arterialsclorosis Ch                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
LB0401 -  ..
LB0402 - Niacin Low-Carbohydrate Diet Reduces Triglycerides Lowers LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
LB0403 - Triglycerides Lower Exercise Weight Loss Fibrates Niacin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
LB0404 - LDL-P Lowered by Exercise Low-Carbohydrate Diet Reduces Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0405 - Carbohydrate Restriction Lowers LDL-P by Lowering Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
LB0406 - 
LB0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0408 - Exercise Lowers LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0410 -       16.  Interventions that lower LDL-P more than LDL-C include                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
LB0411 -            fibrates, niacin, pioglitazone, omega-3 fatty acids,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0412 -            exercise and Mediterranean and low carbohydrate diets.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
LB0413 -            Although statins lower LDL-P, they may leave a significant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0414 -            number of patients above the LDL-P target.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0415 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0416 -               [...above on 131125 0005 patient Internet report that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
LB0417 -               low-carb diet supports raising HDL, lowering                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB0418 -               triglycerides and lowering LDL-P. ref SDS 0 5P5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0420 -                ..
LB0421 -               [...below on 131125 0005 other authorities recommend                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0422 -               lowering triglycerides < 140 signals low LDL-P < 1000
LB0423 -               and that LDL particles are large filled with cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0424 -               (causing LDL-C to rise), rather than small, dense filled                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0425 -               with triglycerides, which cause arterialsclorisis; this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0426 -               can be accomplished using interventions - weight loss,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0427 -               exercise, fibrates niacin. ref SDS 0 PD69                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
LB0429 -                ..
LB0430 -               [...below on 131125 0005 another authority advises that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
LB0431 -               exercise lowers triglycerides. ref SDS 0 T68I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
LB0432 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0434 -  ..
LB0435 - LDL-C Limited Value Misleading Risk Assessment Arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
LB0436 - Metabolic Syndrome TG High HDL Low LDL-P ApoB High LDL-C Low Misleading                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
LB0437 - LDL-C Low Misleading Metabolic Syndrome TG High HDL Low LDL-P ApoB High                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
LB0438 - 
LB0439 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0440 -       17.  Patients with high levels of triglycerides and low HDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0441 -            are likely to have high LDL-P despite normal or low LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0442 -            Such a lipid profile is typical for individuals with the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0443 -            metabolic syndrome.  Studies indicate that these patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0444 -            may benefit most from low carbohydrate diets and that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
LB0445 -            carbohydrate restriction reduces LDL-P.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
LB0446 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0447 -               [...above on 131125 0005 patient Internet report that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
LB0448 -               low-carb diet supports raising HDL, lowering                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB0449 -               triglycerides and lowering LDL-P. ref SDS 0 5P5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0451 -                ..
LB0452 -               [On 150526 1300 Doctor Stewart at VA MCSF recommended                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
LB0453 -               book "Fat Chance" for managing metabolic syndrome toward                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0454 -               better health; book was criticized for lack of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
LB0455 -               scientific founding, and presenting unrealistic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
LB0456 -               remedies. ref SDS 68 ZA9O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
LB0458 -             ..
LB0459 -       18.  LDL-P is not generally used in Europe to assess cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
LB0460 -            risk.  So far, these measurements have primarily been performed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB0461 -            in the United States.  Clinical guidelines in Europe still                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0462 -            recommend measurements of LDL-C to assess risk.  Furthermore,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
LB0463 -            LDL-C is still recommended to assess the effect of statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0464 -            therapy.  However, due to the fact that LDL-C is only a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
LB0465 -            surrogate marker of the availability of atherogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0466 -            lipoproteins, its use may be of limited value.  Measurements of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB0467 -            LDL-P and ApoB are better predictors of cardiovascular risk and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB0468 -            provide a better reflection of the atherogenic potential of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0469 -            lipoproteins.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
LB0471 -             ..
LB0472 -       19.  Questions and Answers on this article...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0473 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0474 -            1.  Reijo Laatkainen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0475 -                22 November 2012                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0477 -                 ..
LB0478 -                Very nice post. Thanks clarifying this pretty                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
LB0479 -                complicated subject.  How convincing is the evidence in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0480 -                your opinion that LDL-P should be the primary parameter                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0481 -                to follow?  Does it add anything on top of ApoB?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0482 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0484 -  ..
LB0485 - Lipid Panal ApoB LDL-P Assess CVD Risk Better than LDL-C Misleading                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0486 - CVD Risk High LDL-P High and LDL-C Low Metabolic Syndrome Means Overweight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
LB0487 - LDL-P High and LDL-C Low High Risk CVD Metabolic Syndrome Means Overweight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
LB0488 - Metabolic Syndrome Means Overweight LDL-P High and LDL-C Low High Risk CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
LB0489 - 
LB0490 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0491 -                Doc's opinion November 22, 2012                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0493 -                 ..
LB0494 -                Thanks Reijo.  The problem with the LDL-P measurements                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0495 -                using NMR spectroscopy is that it is still rather                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
LB0496 -                expensive.  It has been suggested that looking at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
LB0497 -                non-HDL cholesterol (total cholesterol minus HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0498 -                cholesterol), HDL-C and triglycerides may be helpful                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0499 -                when LDL-P and ApoB are not available.  This could be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0500 -                important in patients with the metabolic syndrome,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
LB0501 -                where LDL-C may underestimate risk.  Non-HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
LB0502 -                cholesterol reflects the cholesterol within all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0503 -                lipoprotein particles currently considered                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
LB0504 -                ateherogenic.  Many studies have indicated that it is a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0505 -                better predictor of cardiovascular events than is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
LB0506 -                LDL-C.  However I still think LDL-P measurements may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0507 -                often give important additive information and I my                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
LB0508 -                guess is that it's use will become more common in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0509 -                near future.  However, the clinical utility of these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0510 -                measurements is still limited because the technique is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0511 -                not widely available and it is relatively expensive.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0513 -                 ..
LB0514 -                In clinical terms, LDL-P does not add much to ApoB.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
LB0515 -                LDL-P measures the number of LDL-particles while ApoB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0516 -                measures the number of all atherogenic particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0517 -                (chylomicrons, VLDL,IDL,LDL and Lp(a)).  Usually 85-90%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0518 -                of ApoB represent LDL-particles.  Therefore, in most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0519 -                cases you don't need ApoB if you have LDL-P available                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
LB0520 -                and vice versa.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0522 -  ..
LB0523 - Restates prior recommendation to measure LDL-P and/or ApoB in lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0524 - panel tests, per above. ref SDS 0 C347                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
LB0525 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0526 -                    [On 140201 1159 obtained blood draw for Lipid NMR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
LB0527 -                    test LDL-P at Labcor on Health Testing Centers                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
LB0528 -                    order # 27716. ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
LB0530 -  ..
LB0531 - Article Doc's Opinion by Axel F Sigurdsson continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
LB0532 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0533 -            2.  Richard May                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
LB0534 -                30 January 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
LB0536 -                 ..
LB0537 -                Hi doc, any thoughts on the usefulness of TG/HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0538 -                ratios?  I've heard that TG is a fairly accurate proxy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
LB0539 -                for ApoB count.  Plus TG numbers are easy to obtain.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0540 -                thx!                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
LB0542 -                 ..
LB0543 -                Doc's opinion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
LB0544 -                January 31, 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0545 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0546 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB0547 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
LB06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Doc's Opinion Axel F Sigurdsson MD Research Internet Arterialscloros                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
MK03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
MK0401 -  ..
MK0402 - Metabolic Syndrome Overweght Obese TG/HDL Ratio > 3.5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0403 - Overweght Metabolic Syndrome TG/HDL Ratio > 3.5 Obese                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0404 - Obese Metabolic Syndrome Overweght TG/HDL Ratio > 3.5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0405 - TG/HDL Ratio > 3.5 Apply When LDL-P ApoB Not Available Lipid Panel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
MK0406 - 
MK0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0408 -                @ Richard.  Evidence suggests that there is an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
MK0409 -                association between TG/HDL-C ratio and cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
MK0410 -                risk.  This ratio has also been shown to be associated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0411 -                with insulin resistance.  Thus, the higher your TG and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0412 -                the lower your HDL-C, the greater degree of insulin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0413 -                resistance.  Therefore it may be particularly helpful                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
MK0414 -                in individuals with the metabolic syndrome where the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0415 -                traditional LDL-C often underestimates risk.  A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0416 -                TG/HDL-C ratio above 3.5 has often been used as cutoff                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0417 -                for identifying insulin resistance.  As you say, this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
MK0418 -                ratio is easy to obtain, it is included in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
MK0419 -                traditional lipid panel, and therefore relatively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
MK0420 -                cheap.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0421 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0423 -  ..
MK0424 - This point by Doctor Axel F Sigurdsson seems to align with prior                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
MK0425 - article indicating that TG/HDL-D < 2 ratio lowers risk of
MK0426 - arterialsclorsis and heart attack (CVD event), per above. ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0427 - 5P5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
MK0428 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0429 -            [...below on 131125 0005 review of article by Doctor Attia,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
MK0430 -            seems to support reliance on TG/HDL-C ratio to approximate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0431 -            results of LDL-P testing. ref SDS 0 338N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0433 -             ..
MK0434 -            [...below on 131125 0005 abstract article published by Pub                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0435 -            Med.gov combined parameter, the TG/HDL-C ratio, is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
MK0436 -            beneficial for assessing the presence of small LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0437 -            ref SDS 0 VR5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0439 -             ..
MK0440 -            [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0441 -            submits pending issues to discuss during meeting on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0442 -            131219, ref SDS 47 8N50, and lists TG/HDL-C ratio and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
MK0443 -            LDL-P issues. ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0445 -             ..
MK0446 -            [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0447 -            LDL-P at Labcor on Health Testing Centers order # 27716.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0448 -            ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
MK0450 -             ..
MK0451 -            [On 150526 1300 Doctor Stewart at VA MCSF recommended book                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0452 -            "Fat Chance" for managing metabolic syndrome toward better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0453 -            health; book was criticized for lack of scientific                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
MK0454 -            founding, and presenting unrealistic remedies. ref SDS 68                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
MK0455 -            ZA9O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0456 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0457 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0459 -  ..
MK0460 - Diagram LDL Particle Count Higher Triglycerides Rich/Cholesterol Depleted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
MK0461 - 
MK0462 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0463 - Doctor Sigurdsson cites another source on Internet with PDF                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0464 - diagrams...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
MK0465 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0466 -    3.  Relationship of LDL-C & LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
MK0467 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0468 -              http://www.lipoprotein.org/docs/default-document-library/ldl-c-ldl-p-relationships.ppsx?sfvrsn=0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
MK0470 -         ..
MK0471 -        Otvos JD et al. Am J Cardiol 2002;90(suppl):22i-29i                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
MK0472 -        Cromwell WC et al. J Clin Lipidology. 2007;1(6):583-592.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0474 -         ..
MK0475 -        Framingham Offspring Study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
MK0477 -         ..
MK0478 -        Relations of LDL Particles and LDL Cholesterol to Levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0479 -        HDL Cholesterol and Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
MK0480 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0481 -                                                                    P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
MK0482 -          1800                       180    1800                       180                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0483 -               P                                              P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0484 -                  P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0485 -          1600      P                160    1600         P             160
MK0486 -                       ..
MK0487 -                      P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
MK0488 -          1400                       140    1400     P                 140                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0489 -                    L   P                                L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0490 -                 L     L P                            L     L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0491 -          1200 L           P         120    1200   P           L   L   120                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0492 -                          L  P                    L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0493 -                              L P  P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0494 -          1000                       100    1000                       100                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0495 -                                               L P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
MK0496 -          ===========================       ===========================                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
MK0497 -               20   40   60   80  100             100   200   300   400
MK0498 -                     ..
MK0499 -                    HDL                               Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0501 -         ..
MK0502 -        Narrative says this diagram shows people with same LDL-C level                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0503 -        reported in lipid labs, the number of LDL particles varies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0505 -         ..
MK0506 -        Left graph indicates Framingham Study reported inverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
MK0507 -        relationship between LDL particle count and LDL Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0508 -        levels in relation to rising levels of HDL, seemingly, LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0509 -        and LDL-P become concordant at high levels of HDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0511 -         ..
MK0512 -        Triglyceride diagram on the right shows similar inverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0513 -        relationship with LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0515 -         ..
MK0516 -        Not clear how this analysis evaluates effect of LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0517 -        size on arterialsclorosis caused by small LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0518 -        penetrating endothelial layer lining arteries, discussed below.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
MK0519 -        ref SDS 0 8T5H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0521 -                ..
MK0522 -               [...above on 131125 0005 this article Doctor Sigurdsson                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
MK0523 -               explains discordant lab results for LDL-C high and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
MK0524 -               LDL-particle low is healthy profile, because LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0525 -               particles are large with high concentration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0526 -               cholesterol that cannot penetrate the endothelial layer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0527 -               lining artery walls, and so prevents arterialsclorosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0528 -               ref SDS 0 M95O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0530 -                ..
MK0531 -               [...below on 131125 0005 this article Doctor Attia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
MK0532 -               explains discordant lab results for LDL-C high and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
MK0533 -               LDL-particle low is healthy profile, because LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
MK0534 -               particles are large with high concentration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0535 -               cholesterol that cannot penetrate the endothelial layer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0536 -               lining artery walls, and so prevents arterialsclorosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0537 -               ref SDS 0 FM6L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0539 -                ..
MK0540 -               [...below on 131125 0005 another article presents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
MK0541 -               diagrams of small LDL particles with high concentration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
MK0542 -               of triglycerides and depleted cholesterol, and comparing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
MK0543 -               with large LDL particles with low concentrations of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
MK0544 -               triglycerides and high concentration of cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
MK0545 -               sometimes described as "fluffy" LDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0546 -               ref SDS 0 1V4J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
MK0547 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0549 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK0550 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
MK06 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Eating Academy Peter Attia MD Research Internet Arterialsclorosis Ch                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
NV0401 -  ..
NV0402 - Attia Article Explain Concordant Discordant LDL Particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0403 - 
NV0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0405 - Another article says...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0407 -        The Eating Academy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0408 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0409 -              http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-vi                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0411 -         ..
NV0412 -        By:  Peter Attia, MD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0414 -         ..
NV0415 -        ABOUT THE AUTHOR:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
NV0416 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0417 -            Peter Attia, M.D., is the co-founder and President of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0418 -            Nutrition Science Initiative (NuSI), a non-profit based in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0419 -            San Diego, CA. He received his B.Sc. from Queen's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0420 -            University in Canada and his M.D. from Stanford Medical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0421 -            School in California. After his surgical residency in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
NV0422 -            general surgery at Johns Hopkins he worked as a consultant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0423 -            at McKinsey & Company. He founded NuSI with scientific                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0424 -            journalist Gary Taubes in 2012.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0426 -  ..
NV0427 - This article has no evident date.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0429 -         ..
NV0430 -        First question on this Part VI (6) article is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0431 -        dated............ 30 May 2012                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0432 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0434 -  ..
NV0435 - Cholesterol Essential for Life Background Articles Doctor Attia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
NV0436 - 
NV0437 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0438 -    4.  The straight dope on cholesterol - Part VI                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0439 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0440 -        1.  (Not so) quick refresher on take-away points from previous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0441 -            posts, should you need it:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0442 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0443 -            1.  Cholesterol is "just" another fancy organic molecule in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0444 -                our body but with an interesting distinction: we eat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0445 -                it, we make it, we store it, and we excrete it - all in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0446 -                different amounts.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0448 -                 ..
NV0449 -            2.  The pool of cholesterol in our body is essential for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0450 -                life.  No cholesterol = no life.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0452 -  ..
NV0453 - Cholesterol aids digestion, memory, and immunity, reported in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
NV0454 - connection with guidelines recently released by the American Heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0455 - Association AHA, shown in the record on 131112 1422. ref SDS 42 NF9H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0457 -                 ..
NV0458 -            3.  Cholesterol exists in 2 forms - unesterified or "free"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0459 -                (UC) and esterified (CE) - and the form determines if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0460 -                we can absorb it or not, or store it or not (among                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0461 -                other things).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
NV0463 -  ..
NV0464 - Eating Cholesterol Excreted Not Major Factor Arterialsclorosis CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0465 - Cholesterol Eating Excreted Not Major Factor Arterialsclorosis CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0466 - 
NV0467 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0468 -            4.  Much of the cholesterol we eat is in the form of CE.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0469 -                It is not absorbed and is excreted by our gut (i.e.,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0470 -                leaves our body in stool).  The reason this occurs is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0471 -                that CE not only has to be de-esterified, but it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0472 -                competes for absorption with the vastly larger amounts                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0473 -                of UC supplied by the biliary route.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0475 -                 ..
NV0476 -            5.  Re-absorption of the cholesterol we synthesize in our                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0477 -                body (i.e., endogenous produced cholesterol) is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0478 -                dominant source of the cholesterol in our body.  That                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0479 -                is, most of the cholesterol in our body was made by our                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0480 -                body.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0481 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0482 -                   [On 150221 1039 article pusblished in New York Times                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0483 -                   reports government agency that sets national dietary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0484 -                   guidelines reports new research finding no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0485 -                   appreciable relationship between dietary cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0486 -                   and blood cholesterol. ref SDS 67 NE48                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
NV0488 -                    ..
NV0489 -                   [On 160220 1218 article American Journal of Clinical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0490 -                   Nutrition published study findings that "moderate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0491 -                   intake of cholesterol doesn't seem to increase the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0492 -                   risk of heart disease, even among those people at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0493 -                   higher risk,". ref SDS 73 682I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0495 -                 ..
NV0496 -            6.  The process of regulating cholesterol is very complex                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0497 -                and multifaceted with multiple layers of control.  I've                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0498 -                only touched on the absorption side, but the synthesis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0499 -                side is also complex and highly regulated.  You will                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0500 -                discover that synthesis and absorption are very                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
NV0501 -                interrelated.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0502 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0504 -  ..
NV0505 - Eating Cholesterol Little Effect on Health and Lipid Blood Tests                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0506 - 
NV0507 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0508 -            7.  Eating cholesterol has very little impact on the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0509 -                cholesterol levels in your body.  This is a fact, not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0510 -                my opinion.  Anyone who tells you different is, at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0511 -                best, ignorant of this topic.  At worst, they are a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0512 -                deliberate charlatan.  Years ago the Canadian                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0513 -                Guidelines removed the limitation of dietary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0514 -                cholesterol.  The rest of the world, especially the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0515 -                United States, needs to catch up.  To see an important                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0516 -                reference on this topic, please look here.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0517 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0518 -                   [...below on 131125 0005 article represents eating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
NV0519 -                   food with "trans fatty acids" reduces HDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0520 -                   increases LDL cholesterol. ref SDS 0 I84F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0522 -                    ..
NV0523 -                   [On 150221 1039 article pusblished in New York Times                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0524 -                   reports government agency that sets national dietary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0525 -                   guidelines reports new research finding no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0526 -                   appreciable relationship between dietary cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0527 -                   and blood cholesterol. ref SDS 67 NE48                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
NV0529 -                    ..
NV0530 -                   [On 160220 1218 article American Journal of Clinical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
NV0531 -                   Nutrition published study findings that "moderate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0532 -                   intake of cholesterol doesn't seem to increase the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0533 -                   risk of heart disease, even among those people at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0534 -                   higher risk,". ref SDS 73 682I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0535 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0537 -  ..
NV0538 - LDL HDL Lipoproteins Transport Cholesterol Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0539 - Cholesterol Triglycerides Transported Lipoproteins HDL LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0540 - Triglycerides Cholesterol Transported Lipoproteins HDL LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0541 - Lipoproteins Cholesterol Triglycerides Transported HDL LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0542 - 
NV0543 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0544 -            8.  Cholesterol and triglycerides are not soluble in plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0545 -                (i.e., they can't dissolve in water) and are therefore                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0546 -                said to be hydrophobic.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0548 -                 ..
NV0549 -            9.  To be carried anywhere in our body, say from your liver to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0550 -                your coronary artery, they need to be carried by a special                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0551 -                protein-wrapped transport vessel called a lipoprotein.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0553 -                 ..
NV0554 -           10.  As these "ships" called lipoproteins leave the liver they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
NV0555 -                undergo a process of maturation where they shed much of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0556 -                their triglyceride "cargo" in the form of free fatty acid,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0557 -                and doing so makes them smaller and richer in cholesterol.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
NV0558 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0559 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0561 -  ..
NV0562 - Apoprotiens ApoB in LDL and ApoA-I in HDL Produced in Liver                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0563 - ApoB in LDL and ApoA-I in HDL Apoprotiens Produced in Liver                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
NV0564 - 
NV0565 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0566 -           11.  Special proteins, apoproteins, play an important role                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0567 -                in moving lipoproteins around the body and facilitating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0568 -                their interactions with other cells.  The most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
NV0569 -                important of these are the apoB class, residing on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0570 -                VLDL, IDL, and LDL particles, and the apoA-I class,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0571 -                residing for the most part on the HDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0573 -                 ..
NV0574 -           12.  Cholesterol transport in plasma occurs in both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
NV0575 -                directions, from the liver and small intestine towards                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0576 -                the periphery and back to the liver and small intestine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0577 -                (the "gut").                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0579 -                 ..
NV0580 -           13.  The major function of the apoB-containing particles is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0581 -                to traffic energy (triglycerides) to muscles and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0582 -                phospholipids to all cells.  Their cholesterol is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
NV0583 -                trafficked back to the liver.  The apoA-I containing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
NV0584 -                particles traffic cholesterol to steroidogenic tissues,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0585 -                adipocytes (a storage organ for cholesterol ester) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
NV0586 -                ultimately back to the liver, gut, or steroidogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
NV0587 -                tissue.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0589 -                 ..
NV0590 -           14.  All lipoproteins are part of the human lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
NV0591 -                transportation system and work harmoniously together to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0592 -                efficiently traffic lipids.  As you are probably                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0593 -                starting to appreciate, the trafficking pattern is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
NV0594 -                highly complex and the lipoproteins constantly exchange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0595 -                their core and surface lipids.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
NV0597 -                 ..
NV0598 -           15.  The measurement of cholesterol has undergone a dramatic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0599 -                evolution over the past 70 years with technology at the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
NV0600 -                heart of the advance.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
NV0601 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0602 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0603 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0604 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV0605 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
NV07 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Eating Academy Peter Attia MD Research Internet Arterialsclorosis Ch                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P103 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10401 -  ..
P10402 - Lipid Panel Cholesterol Total, Triglycerides, HDL LDL-C Estimated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10403 - 
P10404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10405 -           16.  Currently, most people in the United States (and the world                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10406 -                for that matter) undergo a "standard" lipid panel, which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10407 -                only directly measures TC, TG, and HDL-C.  LDL-C is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10408 -                measured or most often estimated.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10410 -                 ..
P10411 -           17.  More advanced cholesterol measuring tests do exist to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10412 -                directly measure LDL-C (though none are standardized),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10413 -                along with the cholesterol content of other lipoproteins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10414 -                (e.g., VLDL, IDL) or lipoprotein subparticles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10415 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10417 -  ..
P10418 - LDL-P Test Count Particles and Measure Particle Size - NMR LipoProfile                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10419 - NMR LipoProfile Test Count LDL-P Particles and Measure Particle Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10420 - Lipid Test NMR LipoProfile Count LDL-P Particles and Measure Particle Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10421 - 
P10422 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10423 -           18.  The most frequently used and guideline-recommended test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10424 -                that can count the number of LDL particles is either                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10425 -                apolipoprotein B or LDL-P NMR, which is part of the NMR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10426 -                LipoProfile.  NMR can also measure the size of LDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10427 -                other lipoprotein particles, which is valuable for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10428 -                predicting insulin resistance in drug naïve patients,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10429 -                before changes are noted in glucose or insulin levels.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10431 -                    ..
P10432 -                   [On 140201 1159 obtained blood draw for Lipid NMR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10433 -                   test LDL-P at Labcor on Health Testing Centers order                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10434 -                   # 27716. ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10435 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10437 -  ..
P10438 - LDL Particle Count Lower Reduce Risk Arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10439 - Arterialsclorosis ApoB LDL Particle Penetrates Endothelial Artery Lining                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10440 - Endothelial Artery Lining ApoB LDL Particle Penetrates Arterialsclorosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10441 - 
P10442 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10443 -           19.  The progression from a completely normal artery to a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10444 -                "clogged" or atherosclerotic one follows a very clear                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10445 -                path: an apoB containing particle gets past the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10446 -                endothelial layer into the subendothelial space, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10447 -                particle and its cholesterol content is retained,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10448 -                immune cells arrive, an inflammatory response ensues                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10449 -                "fixing" the apoB containing particles in place AND                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10450 -                making more space for more of them.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10452 -                 ..
P10453 -           20.  While inflammation plays a key role in this process,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10454 -                it's the penetration of the endothelium and retention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10455 -                within the endothelium that drive the process.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10457 -                 ..
P10458 -           21.  The most common apoB containing lipoprotein in this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10459 -                process is certainly the LDL particle.  However, Lp(a)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10460 -                and apoB containing lipoproteins play a role also,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10461 -                especially in the insulin resistant person.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10463 -                 ..
P10464 -           22.  If you want to stop atherosclerosis, you must lower the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10465 -                LDL particle number.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10467 -                 ..
P10468 -           23.  At first glance it would seem that patients with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10469 -                smaller LDL particles are at greater risk for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10470 -                atherosclerosis than patients with large LDL particles,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10471 -                all things equal.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10473 -                 ..
P10474 -           24.  "A particle is a particle is a particle."  If you don't                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10475 -                know the number, you don't know the risk.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10477 -                 ..
P10478 -           25.  To address this question, however, one must look at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10479 -                changes in cardiovascular events or direct markers of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10480 -                atherosclerosis (e.g., IMT) while holding LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10481 -                constant and then again holding LDL size constant.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10482 -                Only when you do this can you see that the relationship                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10483 -                between size and event vanishes.  The only thing that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10484 -                matters is the number of LDL particles - large, small,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10485 -                or mixed.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10486 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10488 -             ..
P10489 -        2.  Concept #8 - Why is it necessary to measure LDL-P, instead of just LDL-C?                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10490 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10491 -            1.  Even when we ...give people a drug that lowers their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10492 -                LDL-P and measure the impact of this intervention -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10493 -                there is always a chance we've done something in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10494 -                addition to "just" lowering LDL-P.   If you've been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10495 -                reading this series, you no doubt know my thoughts on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10496 -                this: while other factors are likely to be involved the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10497 -                pathogenesis of atherosclerosis (e.g., endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10498 -                "health", normal versus abnormal inflammatory response)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10499 -                the primary driver of atherosclerosis is the number of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10500 -                apoB trafficking lipoproteins in circulation, of which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10501 -                LDL particles are the vast majority.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10503 -                    ..
P10504 -                   [On 140201 1159 obtained blood draw for Lipid NMR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10505 -                   test LDL-P at Labcor on Health Testing Centers order                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10506 -                   # 27716. ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10508 -                 ..
P10509 -            2.  The data below should further clarify this association.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10511 -                 ..
P10512 -            3.  What do concordant LDL-C and LDL-P values look like?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10513 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10514 -                Among the two largest studies tracking the association                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10515 -                between cholesterol and atherosclerotic mortality are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10516 -                the Framingham study and the MESA trial (the two                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10517 -                largest trials were AMORIS and INTERHEART).  The figure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10518 -                below, which I've graciously borrowed from Jim Otvos,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10519 -                shows the risk stratification of LDL-C (top) and LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10520 -                (bottom) from the Framingham study and MESA trial,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10521 -                respectively.  As you can see, conveniently, LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10522 -                values in mg/dL are about 10x off from LDL-P values in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10523 -                nmol/L.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10524 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10526 -  ..
P10527 - LDL-P < 1000 nmol/L Target Reduce Risk CVD Event
P10528 - 
P10529 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10530 -            4.  In other words, in the Framingham population, the 20th                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10531 -                percentile value of LDL-C was 100 mg/dL, while the MESA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10532 -                trial found the 20th percentile of the population to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10533 -                have an LDL-P concentration of 1,000 nmol/L.  As you                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10534 -                will see by the end of this post, this "rule of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10535 -                thumb" should never be used to infer LDL-P from LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10536 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10537 -                ...graph showing some data on LDL-C and LDL-P ratios...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10538 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10539 -                   [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10540 -                   LDL-P at Labcor on Health Testing Centers order # 27716.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10541 -                   ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10543 -                 ..
P10544 -            5.  If this were always the case - that is, if LDL-C and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10545 -                LDL-P were always concordant - we could conclude that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10546 -                LDL-C and LDL-P would be of equal value in predicting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10547 -                heart disease.  Obviously this is not the case, or I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10548 -                wouldn't be making such a fuss over the distinction.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10549 -                But how bad is it?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10551 -             ..
P10552 -        3.  What do discordant LDL-C and LDL-P values look like?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10553 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10554 -            The figure below, from the Journal of Clinical Lipidology,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10555 -            shows the cumulative incidence of cardiovascular events                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10556 -            (e.g., myocardial infarction, death) over time in three                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10557 -            sub-populations:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10558 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10559 -            1.  Those with concordant LDL-P and LDL-C (black line);                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10561 -                 ..
P10562 -            2.  Those with discordant LDL-P and LDL-C (LDL-P>LDL-C,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10563 -                shown by the red line);                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10565 -                 ..
P10566 -            3.  Those with discordant LDL-P and LDL-C (LDL-P<LDL-C,
P10567 -                shown by the blue line).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10568 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10570 -  ..
P10571 - CVD Risk Lowest Discordant LDL-P Low < 1060 LDL-C High >= 100
P10572 - Atherosclerosis Lowest CVD Risk LDL-P Low LDL-C High Discordant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10573 - LDL-P Low LDL-C High Discordant Lowest Risk CVD Atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10574 - Discordant LDL-P Low LDL-C High Least Risk CVD Arterialsclorsis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10575 - 
P10576 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10577 -        4.  This analysis was done using a Cox proportional hazard                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10578 -            model and was adjusted for age, sex, and race.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10579 -            steeper the line the more people in that sub-population                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10580 -            died or experienced adverse cardiac events relative to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10581 -            other sub-populations.  In other words, the folks in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10582 -            red group had the worst outcomes, followed by the folks in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10583 -            the black group, followed by the folks in the blue group.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10584 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10585 -            ...graph claimed to be taken from Journal of Clinical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10586 -            Lipidology, but not accessible) evidently showing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10587 -            discordant LDL-P low and LDL-C high provides least risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10588 -            heart attack, arterialsclorsis...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10590 -             ..
P10591 -        5.  What can we infer from these data?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10592 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10593 -            First, we confirm what I alluded to above.  Namely, that a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10594 -            non-zero percent of the population do not have LDL-C and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10595 -            LDL-P values that predict the same level of risk.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10596 -            However, and perhaps more importantly, we get another look                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10597 -            at an important theme of this series: LDL-P is driving                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10598 -            atherosclerotic risk, not LDL-C.   If LDL-P and LDL-C were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10599 -            equally "bad" - even when discordant - you would expect                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10600 -            the blue line to be as steep as the red line (and both to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10601 -            be steeper than the black line). But this is not the case.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10603 -             ..
P10604 -        6.  Let's look at these data parsed out another way.  Below we                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10605 -            see the four possible subgroups, from the top:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10606 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10607 -            1.  Not low LDL-P, low LDL-C (red line);                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10608 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10609 -            2.  Not low LDL-P, not low LDL-C (yellow line);                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10611 -                 ..
P10612 -            3.  Low LDL-P, low LDL-C (black line); and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10614 -                 ..
P10615 -            4.  Low LDL-P, not low LDL-C (blue line).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10616 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10618 -  ..
P10619 - Frequency Discordance About 20% LDL-P Low LCL-C High                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10620 - Discordant Population 20% LDL-P < 1060 "Low" LDL-C >= 100 "High"
P10621 - 
P10622 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10623 -        7.  Note that "low: is defined below the 30th percentile and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10624 -            "not low" is defined as greater than 30th percentile for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10625 -            each variable.   This figure is even more revealing than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10626 -            the one above.  Again, it demonstrates the frequency of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10627 -            discordance (about 20% in this population with these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10628 -            cut-off points), and it shows the importance of LDL-P's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10629 -            predictive power, relative to that of LDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10631 -             ..
P10632 -        8.  In fact, though not statistically significant, the highest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10633 -            risk group has high LDL-P and actually has low LDL-C (I'll                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10634 -            give you a hint of why, below) while the lowest risk group                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10635 -            has low LDL-P and not-low LDL-C.  *This is not a typo.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10637 -  ..
P10638 - Doctors Do Not Know Some People Elevated LDL-C Low Risk CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10639 - 
P10640 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10641 -        9.  The highest risk and lowest risk groups are those with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10642 -            discordant LDL-C and LDL-P.  The high risk group has high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10643 -            LDL-P and low LDL-C, while the lowest risk group has high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10644 -            LDL-C with low LDL-P.  Only a minority of physicians would                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10645 -            know that there is a segment of the population with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10646 -            elevated LDL-C who are at low risk!  The same conclusion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10647 -            will be drawn from the next study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10649 -  ..
P10650 - The graphs, claimed to be taken from Journal of Clinical Lipidology,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10651 - per above, ref SDS 0 KH6J, seem to define LDL-P "low" as < 1060 and
P10652 - LDL-P "high" >= 1060; similarly, LDL-C "low" < 100 and LDL-C "high" >=
P10653 - 100.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10654 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10655 -               [...below on 131125 0005 Attia article further says                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10656 -               90-95% of physicians, including cardiologists, would bet                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10657 -               their own lives that persons with an LDL-C < 70 mg/dL
P10658 -               have no atherosclerotic risk. ref SDS 0 OQ4W                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10660 -                ..
P10661 -               [On 140114 0845 letter to VA asks about ordering lab for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10662 -               LDL-P to test for favorable discordance. ref SDS 49 2140                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10664 -                ..
P10665 -               [On 140116 0814 Doctor Attia's research and analysis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10666 -               cited in letter to VA asking about testing lab for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10667 -               discordance low LDL-P and high LDL-C showing patient                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10668 -               with lowest risk arterialsclorosis mycardial infarction                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10669 -               (heart attack). ref SDS 51 739K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10671 -                ..
P10672 -               [On 140116 0814 letter to medical team cites research                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10673 -               that seems to indicate labs can be ordered to test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10674 -               patients for discordance between high LDL-C and low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10675 -               LDL-P that presents lowest risk for arterialsclorosis,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10676 -               CVD, mycardial infarction. ref SDS 52 H29T                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10678 -                ..
P10679 -               [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10680 -               at Labcor on Health Testing Centers order # 27716,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10681 -               ref SDS 53 KQ4L, showing "concordance" LDL-P 861, LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10682 -               81, HDL 61, TG 68, LDL (pattern A) size = large bouyant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10683 -               protective. ref SDS 53 IM9N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10685 -                ..
P10686 -               [On 140203 1147 obtained blood draw at VA in Martinez,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10687 -               ref SDS 54 X45G, showing LDL-C 93, HDL 58, TG 47,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10688 -               ref SDS 54 IM9N indicating "concordance" LDL-P 626, LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10689 -               (pattern A) size = large bouyant protective. ref SDS 54                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10690 -               QV5G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10692 -                ..
P10693 -               [On 140204 1236 VA letter says patient "misunderstood"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10694 -               the meaning of "discordance" between LDL-C and LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10695 -               from this literature; offers no opposing evidentiary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10696 -               literature. ref SDS 55 SU6H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10698 -             ..
P10699 -       10.  Let's look at an even longer-term follow up study, below.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10700 -            This study followed a Framingham offspring cohort of about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10701 -            2,500 patients over a median time period of almost 15 years                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10702 -            in each of the four possible groups (i.e., high-high,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10703 -            high-low, low-high, and low-low) and tracked event-free                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10704 -            survival.  In this analysis the cut-off points for LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10705 -            and LDL-C were the median population values of 1,414 nmol/L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10706 -            and 131 mg/dL, respectively.  So "high" implies above these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10707 -            values; "low" implies below these values.  Kaplan-Meier                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10708 -            survival curves are displayed over a 16 year period - the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10709 -            steeper the slope of the line the worse the outcome                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10710 -            (survival).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10711 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10712 -            ...graph taken from another study published in Journal of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10713 -            Clinical Lipidology published 22 October 2007...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10714 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10715 -              http://www.lipidjournal.com/article/S1933-2874(07)00283-8/abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10717 -  ..
P10718 - This article says in part...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10719 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10720 -                 Conclusions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10722 -                  ..
P10723 -                 In a large community-based sample, LDL-P was a more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10724 -                 sensitive indicator of low CVD risk than either LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10725 -                 or non?HDL-C, suggesting a potential clinical role                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10726 -                 for LDL-P as a goal of LDL management.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10727 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10728 -            ...evidently showing discordant LDL-P low and LDL-C high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10729 -            provides least risk of heart attack, arterialsclorsis...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10731 -  ..
P10732 - Thus, the Attia article seems to align with the study in the Journal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10733 - of Clinical Lipidology.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10735 -             ..
P10736 -       11.  The same patterns are observed:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10737 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10738 -            1.  LDL-P is the best predictor of adverse cardiac events.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10739 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10740 -            2.  LDL-C is only a good predictor of adverse cardiac                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10741 -                events when it is concordant with LDL-P; otherwise it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10742 -                is a poor predictor of risk.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10744 -             ..
P10745 -       12.  Amazingly the persons with the worst survival had low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10746 -            (below median) LDL-C but high LDL-P.  The patients most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10747 -            likely to have high LDL-P with unremarkable or low LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10748 -            are those with either small LDL particles, or TG-rich /                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10749 -            cholesterol poor LDL particles, or both (e.g., insulin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10750 -            resistant patients, metabolic syndrome patients, T2DM                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10751 -            patients).   This explains why small LDL particles, while                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10752 -            no more atherogenic on a per particle basis than large                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10753 -            particles, are a marker for something sinister.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10755 -  ..
P10756 - Other sources seem to indicate that high LDL-P occurs with HDL low and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10757 - TG high, per above, ref SDS 0 1184, and further above, see para 13 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10758 - 16  ref SDS 0 MN98                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10759 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10760 -               [...below on 131125 0005 another article presents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10761 -               diagrams of small LDL particles with high concentration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10762 -               of triglycerides and depleted cholesterol, and comparing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10763 -               with large LDL particles with low concentrations of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10764 -               triglycerides and high concentration of cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10765 -               sometimes described as "fluffy" LDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10766 -               ref SDS 0 1V4J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10768 -                ..
P10769 -               [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10770 -               at Labcor on Health Testing Centers order # 27716,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10771 -               ref SDS 53 KQ4L, showing LDL-P 861, LDL-C 81, HDL 61, TG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10772 -               68, LDL (pattern A) size = large bouyant protective.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10773 -               ref SDS 53 IM9N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10775 -  ..
P10776 - The Eating Academy, Why Measure LDL-P, continued...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10777 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10778 -       13.  These data were collected from nearly 2,000 patients with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10779 -            diabetes who presented with "perfect" standard cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10780 -            numbers:  LDL-C < 70 mg/dL; HDL-C > 40 mg/dL; TG <150
P10781 -            mg/dL.  However, only in 22% of cases were their LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10782 -            concordant with LDL-C.  That is, in only 22% of cases did                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10783 -            these patients have an LDL-P level below 700 nmol/L.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10785 -             ..
P10786 -       14.  Remember, LDL-C < 70 mg/dL is considered VERY low risk -
P10787 -            the 5th percentile.  Yet, by LDL-P, the real marker of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10788 -            risk, 35% of these patients had more than 1,000 nmol/L and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10789 -            7% were high risk.  When you do this analysis with the same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10790 -            group of patients stratified by less stringent LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10791 -            criteria (e.g., <100 mg/dL) the number of patients in the
P10792 -            high risk group is even higher.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10794 -             ..
P10795 -       15.  The real world tragedy: 90-95% of physicians, including                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10796 -            cardiologists, would bet their own lives that persons with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10797 -            an LDL-C < 70 mg/dL have no atherosclerotic risk.
P10799 -  ..
P10800 - This repeats early comment that most doctors are not aware that LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10801 - provides a stronger signal of CVD risk than LDL-C, per above.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10802 - ref SDS 0 FI3G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10804 -             ..
P10805 -       16.  Tim Russert, shortly before his death, had his LDL-C level                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10806 -            checked.  It was less than 70 mg/dL.  Sadly, his doctors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10807 -            didn't realize they should also have been checking his                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10808 -            LDL-P or apoB.  The figure below, which is from one of Tom                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10809 -            Dayspring's presentations, shows data from this study of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10810 -            nearly 137,000 patients hospitalized for coronary artery                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10811 -            disease between 2000 and 2006.  As you can see, LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10812 -            fails to even reasonably predict cardiovascular disease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10813 -            a patient population sick enough to show up in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10814 -            hospital with chest pain or outright myocardial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10815 -            infarction.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10817 -             ..
P10818 -       17.  Why are LDL-C and LDL-P so often discordant?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10819 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10820 -            Think back to what you learned in a previous post in this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10821 -            series.  LDL particles traffic not only cholesterol ester                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10822 -            but also triglycerides.  Each and every LDL particle has a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10823 -            variable number of cholesterol molecules which, because of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10824 -            constant particle remodeling, is constantly changing.  In                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10825 -            other words, of the several quadrillion LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10826 -            floating in your plasma, no two are carrying the exact                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10827 -            same number of cholesterol molecules. It takes many more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10828 -            cholesterol-depleted LDL particles than cholesterol-rich                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10829 -            LDL particles to traffic a given cholesterol mass (i.e.,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10830 -            number of cholesterol molecules) per volume of plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10831 -            (i.e., per dL).  Core cholesterol mass is related to both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10832 -            LDL particle size (the volume of a sphere is a third power                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10833 -            of the radius - it can take 40-70% more small particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10834 -            than large LDL particles to traffic a given cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10835 -            mass) and the number of TG molecules per LDL particle.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10837 -             ..
P10838 -       18.  TG molecules are larger than cholesterol ester molecules,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10839 -            so as the number of TG molecules per particle increases,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10840 -            the number of cholesterol molecules will be less - in a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10841 -            very non-linear manner.  Regardless of size it takes many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10842 -            more TG-rich LDL particles (which are necessarily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10843 -            cholesterol-depleted) to traffic a given cholesterol mass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10844 -            than TG-poor LDL particles.  The persons with the highest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10845 -            LDL particles typically (though not always) have small LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10846 -            particles that are TG-rich.  These are incredibly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10847 -            cholesterol-depleted LDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10848 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10849 -               [...above on 131125 0005 Doc's opinion written and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10850 -               edited by Axel F Sigurdsson, maintains arterialsclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10851 -               plaque caused by cholesterol depleted and triglyceride                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10852 -               rich LDL particles that are small and dense enough to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10853 -               become trapped within the arterial wall. ref SDS 0 M95O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10855 -                ..
P10856 -               [...below on 131125 0005 report on study in 2007,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10857 -               maintains arterialsclerosis plaque caused by cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10858 -               rich LDL particles within the arterial wall. ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10859 -               UU8M                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10861 -             ..
P10862 -       19.  Summary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10863 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10864 -            Take a look at this figure below from the 2011 Otvos et al.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10865 -            paper I referenced above.  It's a scatterplot of each data                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10866 -            point (i.e., patient) in the study.  The solid red line                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10867 -            shows perfect concordance between LDL-P and LDL-C.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10868 -            dashed red lines show a +/- 12% margin on each side.  Look                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10869 -            at how many dots (remember: each dot represents a person)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10870 -            lie OUTSIDE of the dashed red lines.  Now look again.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10871 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10872 -            ...graph scatter plot comparing concordant LDL-C and LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10873 -            and discordant LDL-C and LDL-P risks of CVD...]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10875 -             ..
P10876 -       20.  When people argue with me about why it's unnecessary to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10877 -            check LDL-P or apoB because it's much easier and cheaper                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10878 -            to check LDL-C, I like to remind them of what Clint                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10879 -            Eastwood would probably say in such a situation:  "You've                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10880 -            got to ask yourself one question: Do I feel lucky? Well,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10881 -            do ya, punk?"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10882 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10883 -            1.  With respect to laboratory medicine, two markers that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10884 -                have a high correlation with a given outcome are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10885 -                concordant - they equally predict the same outcome.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10886 -                However, when the two tests do not correlate with each                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10887 -                other they are said to be discordant.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10889 -                 ..
P10890 -            2.  LDL-P (or apoB) is the best predictor of adverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10891 -                cardiac events, which has been documented repeatedly in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10892 -                every major cardiovascular risk study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10894 -                 ..
P10895 -            3.  LDL-C is only a good predictor of adverse cardiac                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10896 -                events when it is concordant with LDL-P; otherwise it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10897 -                is a poor predictor of risk.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10899 -                 ..
P10900 -            4.  There is no way of determining which individual                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10901 -                patient may have discordant LDL-C and LDL-P without                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10902 -                measuring both markers.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10903 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10904 -                   [...below on 131125 0005 Doctor Attia clarifies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10905 -                   procedure of evaluating discordance between LDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10906 -                   and LDL-P, noting LDL-P can be approximated or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10907 -                   indicated from ration TG/HDL. ref SDS 0 338N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10909 -                 ..
P10910 -            5.  Discordance between LDL-C and LDL-P is even greater in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10911 -                populations with metabolic syndrome, including patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10912 -                with diabetes.  Given the ubiquity of these conditions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10913 -                in the U.S. population, and the special risk such                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10914 -                patients carry for cardiovascular disease, it is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10915 -                difficult to justify use of LDL-C, HDL-C, and TG alone                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10916 -                for risk stratification in all but the most select                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P10917 -                patients.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P10919 -                 ..
P10920 -            6.  This raises the question: if indeed LDL-P is always as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10921 -                good and in most cases better than LDL-C at predicting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10922 -                cardiovascular risk, why do we continue to measure (or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10923 -                calculate) LDL-C at all?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10925 -  ..
P10926 - In an earlier article the same author says in part answering treatment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10927 - questions from another doctor...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10928 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10929 -        The Eating Academy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10930 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10931 -        The straight dope on cholesterol - Part V (5)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10933 -         ..
P10934 -    5.  Concept #7 - Does the size of an LDL particle matter?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10935 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10936 -              http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-v                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P10938 -         ..
P10939 -        Date........................ 7 October 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10941 -  ..
P10942 - Presented here are only parts of very extended questions presented by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10943 - Doctor Tim Smith on 131007, i.e., 2 months ago.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10945 -  ..
P10946 - "A." paragraphs are responses from the author, Doctor Peter Attia,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10947 - also dated 131007.  Doctor Attia's credentials are entered above on a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10948 - subsequent article. ref SDS 0 OM8G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10950 -  ..
P10951 - TG/HDL Ratio with TG < 100 and HDL > 50 Low CVD CAD Risk
P10952 - CVD Risk Triglyceride HDL Ratio Substitute to Measure LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P10953 - Triglyceride HDL Ratio Substitute Measure LDL-P Assess CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10954 - 
P10955 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10956 -        1.  So what clinical relevance can all my nitpicking have? I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P10957 -            want to believe the LDL-P/APO-B story and hopefully apply                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10958 -            it as a powerful risk assessment guide in the treatment of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10959 -            my patients. However, is it anymore powerful than HDL/trig                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10960 -            ratios or CRP?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10962 -             ..
P10963 -            A: Actually it is, although all of those have high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10964 -            correlation, they are incredibly discordant in many folks,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10965 -            especially IR folks. That has been shown in multiple                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10966 -            studies. So in places where LDL-P can't be measured easily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10967 -            (e.g., Canada, Europe), apoB is probably best bet.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10968 -            Thereafter, sure, look at these markers, but understand                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10969 -            the further one goes from particles, the more likely there                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10970 -            is a chance of missing something. Is this chance large?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10971 -            Probably not, especially in non-IR patients.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P10973 -  ..
P10974 - Doctor Attia's response seems to indicate that in the absence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P10975 - direct test results, LDL-P count can be approximated from TG/HDL ratio                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10976 - for non IR (insulin-resistant) patients, which seems to align with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10977 - earlier research above. ref SDS 0 5P5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10978 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10979 -                [...above on 131125 0005 article "Doc's Opinion" by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P10980 -                Doctor Axel F Sigurdsson cites TG/HDL ratio > 2 signals                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10981 -                high risk arterialsclorosis and CVD. ref SDS 0 666G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10983 -                 ..
P10984 -                [...below on 131125 0005 abstract article published by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10985 -                Pub Med.gov combined parameter, the TG/HDL-C ratio, is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P10986 -                beneficial for assessing the presence of small LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10987 -                ref SDS 0 VR5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P10989 -                 ..
P10990 -                [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P10991 -                submits pending issues to discuss during meeting on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10992 -                131219, ref SDS 47 8N50, and lists TG/HDL-C ratio and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P10993 -                LDL-P issues. ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P10995 -  ..
P10996 - Review Questions on Article V continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P10997 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P10998 -        2.  If the LDL-P is discordant with other favourable patterns                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P10999 -            do I still start the patient on a statin?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11001 -             ..
P11002 -            A:  Tough to say.  First, you'd want to know other factors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11003 -            (e.g., apoE status, dietary pattern, sterol pattern).  If                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11004 -            you are evidenced based, though, you probably ought to act                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11005 -            if LDL-P crosses a high risk threshold.  In my personal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11006 -            practice, I do take a pretty nuanced approach and don't                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11007 -            necessary turn to meds in this setting if everything is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11008 -            great (e.g., no IR, very low CRP, very low MPO/LpPLA2), but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11009 -            I may look at and track other studies, such as CIMT.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11011 -             ..
P11012 -        3.  If already on a statin do I start a use a bile acid resin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11013 -            if LDL-P remains high?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P11015 -             ..
P11016 -            A:  Depends on synthesis and absorption status and a host                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11017 -            of other abnormalities as to which is the better second                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11018 -            line drug - in most ezetimibe (zetia) would be the choice.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11020 -  ..
P11021 - Comment...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P11023 -  ..
P11024 - Interesting that "cholesterol CVD expert" - here, Doctor Attia -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11025 - recommends ezetimibe (zetia) for secondary drug treating high risk CAD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11026 - patients.  Aligns with work plan currently proposed by Doctor Alba,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11027 - shown in Karen's letter received earlier today, per above, ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11028 - V154, reflecting Progress Notes from meeting with Doctor Alba, 131121                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11029 - 0930, ref SDS 44 S26O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P11030 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11031 -            [...above on 131125 0005 research found ezetimibe (zetia)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P11032 -            mg added to Atorvastatin 20 mg yielded significantly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11033 -            greater changes to HDL and Triglycerides (TG), than taking                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11034 -            Atorvastatin in higher doses, e.g., 20 or 40 mg.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P11035 -            ref SDS 0 CO56                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P11037 -  ..
P11038 - Review Questions on Article V continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P11039 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11040 -        4.  Probably not if the statin is mainly operating as an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11041 -            anti-inflammatory agent irrespective of its cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11042 -            effects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11044 -             ..
P11045 -            A:  I know of no clinical trial evidence supporting that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11046 -            the benefit of statins is anti-inflammatory - that is just                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11047 -            a plausible hypothesis at this time.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11048 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11050 -             ..
P11051 -        5.  Is LDL-P more relevant to established CAD than primary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P11052 -            prevention?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11054 -             ..
P11055 -            A: Both are LDL-P diseases AFCAPS TexCAPS was primary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11056 -            prevention and apoB was the best marker of risk and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P11057 -            establish a goal of treatment.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P11058 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11060 -             ..
P11061 -        6.  Can guidelines and targets really be formed if LDL-P is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11062 -            really just the smoke and not the fire?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11064 -             ..
P11065 -            Guidelines are based on evidence that exists and many now                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11066 -            utilize apoB/LDL-P in a variety of functions.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P11068 -             ..
P11069 -            To believe the LDL-P risk story I need a better mechanism                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11070 -            than a simple concentration gradient, especially in a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11071 -            highly regulated receptor mediated environment.  Otherwise,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11072 -            I fear we may fall into the same logical traps as the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11073 -            saturated fat and total cholesterol debates.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P11075 -             ..
P11076 -            A:  Perhaps, but that will take years of studies to "prove"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11077 -            anything in medicine.  In my humble opinion - which you can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11078 -            freely choose to disregard without hurting my feelings - in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11079 -            2013 ignoring LDL-P, at least in most people, may not be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11080 -            the best strategy for mitigating heart disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P11081 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11082 -                [On 131216 0028 letter to Doctor Alba and medical team                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P11083 -                submits pending issues to discuss during meeting on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11084 -                131219, ref SDS 47 8N50, and lists TG/HDL-C ratio and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P11085 -                LDL-P issues. ref SDS 47 6T49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11086 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11087 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11089 -  ..
P11090 - TG/HDL Ratio < 2 Indicates Dense/Small LDL Particle Size
P11091 - LDL Particle Size Assessment Triglycerides/HDL Ratio                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11092 - 
P11093 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11094 - Another article says...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P11095 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11096 -        Pub Med.gov                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11097 -        US National Library of Medicine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11098 -        National Institute of Health                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11100 -         ..
P11101 -    6.  Assessment of LDL particle size by triglyceride/HDL-                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P11102 -        cholesterol ratio in non-diabetic, healthy subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P11103 -        without prominent hyperlipidemia. Maruyama C, Imamura                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P11104 -        K, Teramoto T.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11105 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11106 -        2003;10(3):186-91                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P11107 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11108 -              http://www.ncbi.nlm.nih.gov/pubmed/14564088                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P11110 -         ..
P11111 -        Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11113 -         ..
P11114 -        Small, dense low-density lipoprotein (LDL) is an atherogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11115 -        lipoprotein because of its susceptibility to oxidative                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P11116 -        modification.  However, evaluating LDL size requires highly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11117 -        sophisticated techniques.  We investigated potentially                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P11118 -        convenient biochemical parameters for assessing the presence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11119 -        small, dense LDL.  Thirty-nine male subjects, who had been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P11120 -        involved in a work-site health promotion program, were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P11121 -        recruited.  Subjects were divided into two groups: normal LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11122 -        size (> 25.5 nm, Normal LDL group) and small LDL (</= 25.5 nm,
P11123 -        Small LDL group).  Significant negative correlations were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11124 -        observed between LDL size and both triglyceride (TG) (p <0.001)
P11125 -        and remnant-like particle cholesterol concentrations (p <
P11126 -        0.01), while there was a significant positive correlation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11127 -        between LDL size and the high density lipoprotein cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11128 -        (HDL-C) concentration (p < 0.01).  The TG concentration was a
P11129 -        negative and the HDL-C concentration a positive independent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11130 -        variable predicting LDL size in multiple regression analysis (p                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11131 -        < 0.0001).  Seventy-five percent of the Small LDL group had
P11132 -        TG/HDL-C ratios higher than 0.9 using mmol/L or 2.0 using                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11133 -        mg/dL, while only 25% of the normal LDL group had ratios above                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P11134 -        the levels (p = 0.0013).  A combined parameter, the TG/HDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P11135 -        ratio, is beneficial for assessing the presence of small LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P11137 -  ..
P11138 - This aligns with earlier research above by Doctor Attia, ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P11139 - 338N; further aligns with article by Doctor Sigurdsson, ref SDS 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P11140 - 666G, and initially shown in earlier research article indicating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P11141 - TG/HDL-D < 2 ratio lowers risk of arterialsclorsis and heart attack
P11142 - (CVD event), per above. ref SDS 0 5P5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P11143 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11144 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11145 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11146 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P11147 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P112 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P203 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P20401 -  ..
P20402 - Exercise HDL Increase with Orange and Cranberry Juice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20403 - Orange Juice Exercise Increase HDL and Cranberry                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20404 - HDL Exercise Increase with Orange and Cranberry Juice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20405 - 
P20406 - Research found... ref SDS 0 R49J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P20407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20408 -        The American Journal of Clinical Nutrition                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20410 -         ..
P20411 -        Accepted date......................... 10 March 2000                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P20413 -         ..
P20414 -    7.  HDL-cholesterol-raising effect of orange juice in subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20415 -        with hypercholesterolemia1,2,3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P20416 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20417 -              http://ajcn.nutrition.org/content/72/5/1095.long                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20419 -         ..
P20420 -        Elzbieta M Kurowska, J David Spence, John Jordan, Stephen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P20421 -        Wetmore, David J Freeman, Leonard A Piché, and Paula Serratore                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P20422 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20423 -        1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P20424 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20425 -            1.  Background - Orange juice - a rich source of vitamin C,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20426 -                folate, and flavonoids such as hesperiding induces                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20427 -                hypocholesterolemic responses in animals.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P20429 -                 ..
P20430 -            2.  Objective: We determined whether orange juice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P20431 -                beneficially altered blood lipids in subjects with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20432 -                moderate hypercholesterolemia.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P20434 -                 ..
P20435 -            3.  Design:  The sample consisted of 16 healthy men and 9                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P20436 -                healthy women with elevated plasma total and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P20437 -                LDL-cholesterol and normal plasma triacylglycerol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P20438 -                concentrations.  Participants incorporated 1, 2, or 3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P20439 -                cups (250 mL each) of orange juice sequentially into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P20440 -                their diets, each dose over a period of 4 wk.  This was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20441 -                followed by a 5-wk washout period.  Plasma lipid,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P20442 -                folate, homocyst(e)ine, and vitamin C (a compliance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P20443 -                marker) concentrations were measured at baseline, after                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20444 -                each treatment, and after the washout period.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P20445 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20447 -  ..
P20448 - Orange Juice Increased HDL 21% 750 ML Per Day Over 4 Weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P20449 - HDL 21% Orange Juice Increased 750 ML Per Day Over 4 Weeks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P20450 - 
P20451 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20452 -            4.  Results:  Consumption of 750 mL but not of 250 or 500                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P20453 -                mL orange juice daily increased HDL-cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P20454 -                concentrations by 21% (P < 0.001), triacylglycerol
P20455 -                concentrations by 30% (from 1.56 ± 0.72 to 2.03 ± 0.91                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P20456 -                mmol/L; P < 0.02), and folate concentrations by 18% (P
P20457 -                < 0.01); decreased the LDL-HDL cholesterol ratio by 16%
P20458 -                (P < 0.005); and did not affect homocyst(e)ine
P20459 -                concentrations.  Plasma vitamin C concentrations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20460 -                increased significantly during each dietary period                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20461 -                (2.1, 3.1, and 3.8 times, respectively).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P20463 -                 ..
P20464 -            5.  Conclusions:  Orange juice (750 mL/d) improved blood                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P20465 -                lipid profiles in hypercholesterolemic subjects,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20466 -                confirming recommendations to consume >= 5 - 10                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20467 -                servings of fruit and vegetables daily.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20469 -  ..
P20470 - The report seems to say HDL increased 21% with 750 ML/Day of orange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P20471 - juice for 4 weeks. ref SDS 0 9373                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P20473 -  ..
P20474 - The report does not indicate that HDL continues to increase 21% or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P20475 - some other amount using orange juice another 4 weeks, 8 weeks, etc.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P20476 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20477 -            [...below on 131125 0005 Pub Med article reports consuming                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P20478 -            eggs increases HDL. ref SDS 0 XG69                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P20480 -             ..
P20481 -            [On 140114 0845 notified VA added orange juice to diet for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P20482 -            raising HDL and lowering triglycerides. ref SDS 50 2197                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P20484 -             ..
P20485 -            [On 140514 0950 VA lab shows HDL increased 30%, 140514                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P20486 -            0950, ref SDS 58 IM9N, with orange juice 1+ gallon per week                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P20487 -            for 3 months. ref SDS 58 LO4J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P20489 -             ..
P20490 -            [On 140515 2043 letter to VA notifies medical team that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20491 -            orange juce increase correlates with rise in HDL,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P20492 -            ref SDS 62 PQXS, similar to findings of clinical study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P20493 -            reviewed on 131125. ref SDS 0 R48K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P20495 -             ..
P20496 -            [On 140519 0800 Progress Notes for meeting at VA report                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20497 -            customer increased intake of orange juice; fails to mention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P20498 -            correlation with rise in HDL, nor correlation with study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P20499 -            ref SDS 63 PB4I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P20500 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20501 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20502 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20503 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20504 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P20505 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P206 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P303 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P30401 -  ..
P30402 - Exercise Jim Fixx Infrequent Caused Heart Attack Running 10 Miles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30403 - Fixx Jim Myocadial Infarction Heart Attack Running 10 Miles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P30404 - Jim Fixx Died CVD While Running 10 Miles Training for Marathons                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30405 - 
P30407 -  ..
P30408 - There is a lot of research showing that aerobic exercise alone will                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30409 - not avoid cardio vascular disease (CVD), including myocardial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P30410 - infarction (heart attack), and death.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30412 -  ..
P30413 - Author Jim Fixx dies on July 20, 1984.  His body was found on the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30414 - side of the road where he was training with a 10 mile run, and was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30415 - presumably in good shape from prior training and involvement in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30416 - running events, including marathons.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30418 -  ..
P30419 - Research found...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30420 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30421 -        Active                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P30422 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30423 -    8.  The Legacy of Jim Fixx                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P30424 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30425 -              http://www.active.com/articles/the-legacy-of-jim-fixx                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30427 -             ..
P30428 -        2.  James F Fixx authored The Complete Book of Running, at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30429 -            the time of its publication in 1977 the best-selling                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30430 -            non-fiction hardcover book ever.  The book's bright red                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30431 -            cover featured Fixx's own running legs.  The Complete Book                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30432 -            of Running, still in print, eventually sold a million                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30433 -            copies, both benefiting from and helping to launch the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30434 -            running boom.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P30436 -             ..
P30437 -        3.  Writing from personal experience, Fixx trumpeted the health                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30438 -            benefits of running. After starting to jog at age 35, he                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30439 -            quit smoking and shed 50 pounds.  Yet at age 52, Fixx                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30440 -            collapsed while running on a tree-shaded road in Vermont.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30441 -            He was found lying beside the road, dead of a heart attack.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30442 -            The date was July 20, 1984.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30444 -             ..
P30445 -        4.  Doctor Thompson admits that runners are more at risk during                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30446 -            the hour or so a day they train and particularly if they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30447 -            run marathons.  But the remainder of the day, he says, they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30448 -            are much less at risk than the general population and can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30449 -            actually extend and improve their lives and lifestyle.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30451 -             ..
P30452 -        5.  In his classic study of Harvard alumni, Ralph S                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P30453 -            Pafffenbarger, Jr MD found that we can live an extra                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30454 -            two-plus years if we do even minimal exercise.  Other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30455 -            researchers, including those connected with Kenneth H.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30456 -            Cooper, M.D., believe that we actually may be able to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30457 -            extend our lifespan six to nine years through exercise and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30458 -            attention to diet!                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P30460 -             ..
P30461 -        6.  Jim Fixx may have done just that, given the fact that his                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30462 -            father died of a heart attack at age 43, and he survived                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30463 -            nine years longer to age 52.  He might have lived longer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30464 -            had he listened to Dr Cooper, who urged him to take a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30465 -            stress test during one visit to the Cooper Clinic in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30466 -            Dallas.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30468 -             ..
P30469 -        7.  Despite having cholesterol levels above 250, Fixx demurred                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30470 -            for reasons we can only guess at.  In the several months                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30471 -            before his death, Fixx ignored what hindsight reveals were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30472 -            the warning signs of advanced coronary artery disease.  An                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30473 -            autopsy revealed blockage in Fixx's three main arteries of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30474 -            95 percent, 85 percent and 50 percent.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30476 -  ..
P30477 - This is not helpful saying "cholesterol levels above 250," - was this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30478 - total cholesterol, LDL, triglycerides?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30480 -  ..
P30481 - Fixx blood pressure and heart rate are not reported in the article.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30482 - Were these signals of mounting CVD?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30484 -  ..
P30485 - Did Fixx have a coronary CTA to evaluate atherosclerosis, as news                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30486 - commentator Tim Russert did, per below? ref SDS 0 N73K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30488 -  ..
P30489 - The record is unclear how often Fixx ran 10 miles a day - was it 7                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30490 - days a week, which would lower LDL-P, per above, ref SDS 0 QP9F, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30491 - TG, ref SDS 0 JV5O, and increase HDL to drive regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P30492 - atherosclerotic plaques?  Or was Fixx able to train only 4 or even                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30493 - less days a week, which would not arrest progression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P30494 - atherosclerosis? ref SDS 0 XY7L  Did he do regular running less than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30495 - 10 miles per day, say 3 - 5 miles per day?  Did his work and travel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30496 - schedule cause him to go for days and weeks without running, then do                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30497 - concentrated training to prepare for a marathon?  People with busy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P30498 - schedules can believe they are training more than is actually                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P30499 - occurring.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P30501 -  ..
P30502 - Welch case suggests level of effort must reach certain thresholds in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30503 - order for aerobic exercise through hiking and running to improve                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P30504 - cholesterol lipid profile enough that lowers risks of CVD/CAD events.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30506 -  ..
P30507 - See spreadsheet at...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P30508 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30509 -              F:\05\00003\SM\CC\BNKG\120216cc\130101cc\hiking_miles_3.xlsx                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P30511 -  ..
P30512 - Did Fixx consider hiking instead of running 10 miles per day to reduce                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P30513 - high stress on coronary system while increasing HDL and lowering TG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P30514 - for regression of atherosclerosis that ultimately killed him?  Welch                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P30515 - discovered CVD before getting heart attack by hiking, reported to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P30516 - Doctor Lee at the VA on 090908 1130. ref SDS 3 MY4N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P30517 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30518 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30519 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30520 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30521 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P30522 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P306 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P403 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P40401 -  ..
P40402 - Russert HDL Low TG High BP Elevated Overweight Enlarged Heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P40403 - 
P40404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40405 - Another article...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40407 -        Controlled Carbohydrate Nutrition                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P40408 -        Jacqueline A Eberstein, RN                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40410 -         ..
P40411 -        In the News                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40413 -         ..
P40414 -        Date........................ Not listed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P40416 -         ..
P40417 -    9.  What We Can Learn From Tim Russert's Death                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40418 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40419 -              http://www.controlcarb.com/ccn-news-Tim%20Russert.htm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P40420 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40421 -        1.  Once getting over the initial shock of hearing about the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40422 -            sudden, premature death of Tim Russert of heart disease my                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40423 -            next thought was too bad he was overweight and didn't                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P40424 -            adequately address that risk. He was medicated for high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40425 -            blood pressure but still had an enlarged heart, likely a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40426 -            sign his blood pressure was not optimally controlled.  He                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40427 -            certainly was given statins long ago to manage cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40428 -            and LDL.  His levels of these were likely quite low.  Yet                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40429 -            he still became one of the many who die each year from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40430 -            their first heart attack, whose first symptom is sudden                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40431 -            death.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40433 -             ..
P40434 -        2.  First, I admit that I have no direct or personal knowledge                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40435 -            of his medical condition.  I am expressing a somewhat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P40436 -            educated opinion.  Second, as sad as it is for his family                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40437 -            and colleagues at his sudden loss, it shouldn?t be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P40438 -            completely surprising.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40440 -             ..
P40441 -        3.  While listening to commentary the days following his death                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40442 -            I heard comments that his stress test was normal and he                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40443 -            exercised.  What was rarely mentioned was his weight.  I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40444 -            think this is a perfect example of just how many of us                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40445 -            don't perceive excess fat, especially belly fat, as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P40446 -            dangerous and life-threatening. No amount of medications                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40447 -            are a guarantee to offset risk factors related to excess                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40448 -            body fat especially belly fat and its dangers.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P40450 -             ..
P40451 -        4.  We know that increased belly fat is a component of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P40452 -            metabolic syndrome an insulin resistance syndrome that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40453 -            leads to diabetes and heart disease. Visceral fat around                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40454 -            the mid-section and deep into the abdomen is metabolically                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40455 -            active producing numerous harmful chemicals that increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40456 -            inflammation in the body. Inflammation is thought to be the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P40457 -            main cause of plaque formation in the arteries.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P40459 -  ..
P40460 - Russert High TG Low HDL High Blood Pressure Overweight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P40461 - 
P40462 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40463 -        5.  The latest info from his physician quoted in the New York                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40464 -            Times is that Mr Russert recently needed more aggressive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40465 -            blood pressure management.  Additionally, he had high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P40466 -            triglycerides and low HDL and an increased waist                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P40467 -            circumference--all symptoms of the metabolic syndrome and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40468 -            important markers for heart attack risk.  There is no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P40469 -            mention of an evaluation for elevation of blood sugar and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40470 -            insulin after eating.  This allows a physician to diagnose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40471 -            artery-damaging diabetes at an earlier stage and is simply                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40472 -            not done often enough.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40474 -             ..
P40475 -        6.  If Mr Russert was attempting to lose weight he was likely                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40476 -            advised the usual: low calories, low saturated fat, high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40477 -            carbs the very diet that will increase the abnormal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P40478 -            metabolism he suffered from.  Yet the care he received is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40479 -            the standard in the US.  Since there are no good drugs that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P40480 -            lower triglycerides and increase HDL the way a low carb                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40481 -            lifestyle can, these factors are often not addressed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40482 -            effectively.  One reason is the phobia about dietary fat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40483 -            and cholesterol and the concentration on lowering LDL with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40484 -            drugs as the major risk.  To read more info explaining why                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40485 -            low carb should be the treatment of choice for metabolic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P40486 -            syndrome click here.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40488 -             ..
P40489 -        7.  It's about much more than cholesterol and LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P40491 -             ..
P40492 -        8.  Simply lowering cholesterol and LDL cholesterol with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40493 -            medications can cause a false sense of security leading                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P40494 -            many to feel that they have addressed their major risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40495 -            factors for heart disease.  This prevents them from making                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40496 -            the lifestyle changes that can truly decrease their risks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40497 -            Unfortunately, many people aren't even fully evaluated for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P40498 -            other risk factors that can play an important role in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P40499 -            development of cardiovascular disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P40500 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P40501 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P503 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P50401 -  ..
P50402 - Risk Factors Cardiovascular Disease Blocked Artery Heart Attack                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P50403 - Cardiovascular Disease Blocked Artery Heart Attack Risk Factors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P50404 - Arterialsclorosis Myocardial Infarction Heart Attack Risk Factors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P50405 - 
P50406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P50407 -        9.  There are many factors that play a role in cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P50408 -            disease that must be evaluated and addressed. They include:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P50409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P50410 -            1.  Abnormal blood sugar and insulin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P50412 -                 ..
P50413 -            2.  Smoking                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P50415 -                 ..
P50416 -            3.  Low HDL and high triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P50418 -                 ..
P50419 -            4.  High blood pressure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P50421 -                 ..
P50422 -            5.  Excess body fat especially around the mid-section                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P50424 -                 ..
P50425 -            6.  Inflammation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P50427 -                 ..
P50428 -            7.  Metabolic syndrome                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P50430 -                 ..
P50431 -            8.  High fibrinogen levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P50433 -                 ..
P50434 -            9.  High homocysteine levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P50436 -                 ..
P50437 -           10.  Predominately small, dense LDL particle size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P50439 -                 ..
P50440 -           11.  Periodontal disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P50442 -                 ..
P50443 -           12.  Couch potato lifestyle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P50445 -                 ..
P50446 -           13.  Chronic stress                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P50448 -                 ..
P50449 -           14.  Sleep apnea                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P50451 -                 ..
P50452 -           15.  Nutrient deficiency                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P50454 -                 ..
P50455 -           16.  Elevated lipoprotein a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P50457 -             ..
P50458 -       10.  The process of plaque formation takes many years to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P50459 -            develop. When unstable plaque in the artery wall ruptures                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P50460 -            into the lumen of the artery a clot forms and causes death                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P50461 -            of the heart muscle because of lack of blood supply                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P50462 -            carrying oxygen and nutrients to the area. This happens                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P50463 -            suddenly.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P50464 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P50465 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P505 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P603 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60401 -  ..
P60402 - Russert CT Score 210 Should be 0                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60403 - Artherosclerosis Coronary CTA and IVUS Measure Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60404 - Coronary CTA and IVUS Arterialsclorsis Plaque Measure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60405 - IVUS and Coronary CTA Arterialsclorsis Plaque Measure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60406 - 
P60407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60408 -       11.  A CT scan of the chest can measure the calcium present in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60409 -            the coronary arteries yet this test is often not done.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60410 -            According to the New York Times Mr Russert had the scan                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60411 -            done in 1998 with a score of 210.  It should be 0.  There                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60412 -            is no mention of a repeat test to see if statin therapy had                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60413 -            been effective or if his disease was progressing.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60415 -  ..
P60416 - Below, this article concludes. ref SDS 0 N738                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60418 -  ..
P60419 - What about CT test to assess level of plaque build up due to LDL 249,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60420 - on lipid panel performed on 131015 0724. ref SDS 38 IM9N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60421 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60422 -               [On 140515 letter to medical team reports visiting San                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60423 -               Francisco Medical Center Radiology Department on doing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60424 -               coronary CTA assess regression of atherosclerotic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60425 -               plaques resulting from interventions, including CABG +4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60426 -               on 091022, with subsequent high levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60427 -               hyperlipedimeia (LDL 249), followed by dramatic decline                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60428 -               in LDL-P and rise of HDL. ref SDS 59 YM41                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60430 -                ..
P60431 -               [On 151019 CCTA test performed and showed all bypass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60432 -               grafts are patent. ref SDS 69 JW8O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60434 -                ..
P60435 -               [On 160104 0855 Doctor Jha, attending physician for this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60436 -               CCTA imaging study, advised that standard of practice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60437 -               for radiology reporting is to present any and all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60438 -               blockages of any kind observable in CCTA scan imaging;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60439 -               so, in this case, since none are reported, the CCTA test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60440 -               on 151019, ref SDS 69 JW8O, can correctely be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60441 -               interpretted to mean there are no blockages, plaques,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60442 -               stenosis of any kind evident from the scan file record.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60443 -               ref SDS 70 AA64                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60445 -                ..
P60446 -               [On 160107 2042 letter to Doctor Jha submits proposed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60447 -               language for addendum to clarify findings on CCTA study,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60448 -               ref SDS 71 8P70, originally performed on 151019.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60449 -               ref SDS 69 JW8O                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60451 -                ..
P60452 -               [On 160113 2234 received letter from Doctor Jha saying                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60453 -               the radiology faculty approved issuing an addendum.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60454 -               ref SDS 72 A85F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60456 -                ..
P60457 -               [On 151019 0930 an undated addendum was added to report                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60458 -               on CCTA test on 151019, that clarifies findings and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60459 -               impressions by establishing CCTA found no evidence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60460 -               plaque, stenosis, occlusion of any kind or amount.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60461 -               ref SDS 69 SU4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60462 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60464 -  ..
P60465 - Research found CT tests for arterslcorosis...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60466 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60467 -            JACC Cardiovascular Imaging                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60468 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60469 -            Volume 4, Issue 5 May 2011                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60470 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60471 -            Coronary Atherosclerosis Imaging by Coronary CT Angiography                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60472 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60473 -            Current Status, Correlation With Intravascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60474 -            Interrogation and Meta-Analysis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60475 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60476 -              http://imaging.onlinejacc.org/article.aspx?articleid=1110114                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60478 -             ..
P60479 -            By:  Szilard Voros, MD?; Sarah Rinehart, MD?; Zhen Qian,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60480 -            PhD?; Parag Joshi, MD?; Gustavo Vazquez, MD?; Collin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60481 -            Fischer, MD?; Pallavi Belur, DO?; Edward Hulten, MD, MPH?;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60482 -            Todd C. Villines, MD?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60484 -             ..
P60485 -            Author Information                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60487 -             ..
P60488 -            Piedmont Heart Institute, Atlanta, Georgia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60489 -            - Walter Reed Medical Center, Washington, DC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60490 -            Dr. Voros has received research grants from for Abbott                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60491 -            Vascular, Volcano Inc., Vital Images, Siemens Medical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60492 -            Solutions, and Toshiba America Medical Systems. All other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60493 -            authors have reported that they have no relationships to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60494 -            disclose.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60496 -             ..
P60497 -            Reprint requests and correspondence: Dr. Szilard Voros,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60498 -            Piedmont Heart Institute, 1968 Peachtree Road, NW,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60499 -            Atlanta, Georgia 30309                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60501 -             ..
P60502 -            American College of Cardiology Foundation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60504 -             ..
P60505 -            J Am Coll Cardiol Img. 2011;4(5):537-548.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60506 -            doi:10.1016/j.jcmg.2011.03.006                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60507 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60508 -            1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60509 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60510 -                Coronary computed tomography angiography (CTA) allows                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60511 -                coronary artery visualization and the detection of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60512 -                coronary stenoses.  In addition; it has been suggested                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60513 -                as a novel, noninvasive modality for coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60514 -                atherosclerotic plaque detection, characterization, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60515 -                quantification.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60517 -                 ..
P60518 -            2.  Emerging data show that coronary CTA - based                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60519 -                semi-quantitative plaque characterization and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60520 -                quantification are sufficiently reproducible for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60521 -                clinical purposes, and fully quantitative approaches                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60522 -                may be appropriate for use in clinical trials.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60523 -                Furthermore, several lines of investigation have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60524 -                validated plaque imaging by coronary CTA against other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60525 -                imaging modalities such as intravascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60526 -                ultrasound/"virtual histology" and optical coherence                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60527 -                tomography, and there are emerging data using                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60528 -                biochemical modalities such as near-infrared                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60529 -                spectroscopy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60530 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60531 -                   [On 140515 letter to medical team reports visiting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60532 -                   San Francisco Medical Center Radiology Department on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60533 -                   doing coronary CTA assess regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60534 -                   atherosclerotic plaques resulting from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60535 -                   interventions, including CABG +4 on 091022, with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60536 -                   subsequent high levels of hyperlipedimeia (LDL 249),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60537 -                   followed by dramatic decline in LDL-P and rise of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60538 -                   HDL. ref SDS 59 YM41                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60540 -                 ..
P60541 -            3.  Finally, clinical validation in patients with acute                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60542 -                coronary syndrome and in the outpatient setting has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60543 -                shown incremental value of CTA-based plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60544 -                characterization for the prediction of major                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60545 -                cardiovascular events.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60547 -                 ..
P60548 -            4.  With recent developments in image acquisition and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60549 -                reconstruction technologies, coronary CTA can be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60550 -                performed with relatively low radiation exposure.  With                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60551 -                further technological innovation and clinical research,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60552 -                coronary CTA may become an important tool in the quest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60553 -                to identify vulnerable plaques and the at-risk patient.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60555 -                 ..
P60556 -            5.  Abbreviations And Acronyms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60557 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60558 -                1.  ACS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60559 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60560 -                    acute coronary syndrome                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60562 -                     ..
P60563 -                2.  CTA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60564 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60565 -                    computed tomography angiography                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60567 -                     ..
P60568 -                    Coronary CT angiography is the test we need.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60569 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60570 -                           415 353-2573                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60571 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60572 -                           415 514 8888                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60573 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60574 -                           kimberly.nyberg@ucsfmedctr.org                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60576 -                     ..
P60577 -                3.  IVUS/VH                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60578 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60579 -                    intravascular ultrasound/"virtual histology"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60581 -                     ..
P60582 -                4.  NIRS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60583 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60584 -                    near-infrared spectroscopy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60586 -                     ..
P60587 -                5.  OCT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60588 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60589 -                    optical coherence tomography                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60591 -                     ..
P60592 -                6.  TCFA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60593 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60594 -                    thin-cap fibroatheroma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60596 -                 ..
P60597 -            6.  Molecular and cellular events leading to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60598 -                atherosclerosis, such as lipoprotein deposition,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60599 -                inflammation, smooth muscle cell proliferation,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60600 -                apoptosis, necrosis, calcification, and fibrosis, cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60601 -                specific compositional and geometric changes in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60602 -                coronary vessels (1).  Some of these changes, such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60603 -                increased plaque volume, positive remodeling,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60604 -                lipoprotein deposition in the form of noncalcified                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60605 -                plaques, and calcification, can be detected by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60606 -                contrast-enhanced coronary computed tomography                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60607 -                angiography (CTA).  In this article, we review                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60608 -                qualitative and quantitative plaque characterization                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60609 -                and serial plaque imaging with coronary CTA.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60611 -                 ..
P60612 -            7.  Coronary Plaque Imaging By Coronary CTA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60613 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60614 -                Coronary CTA is typically performed on multidetector CT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60615 -                systems after the injection of iodine contrast media                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60616 -                for opacification of the lumen.  Current multidetector                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60617 -                CT systems have an isotropic spatial resolution of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60618 -                approximately 400 to 600 ms and temporal resolution of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60619 -                approximately 83 to 175 ms (2).  Coronary arterial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60620 -                plaques are typically reviewed in either axial or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60621 -                multiplanar reformatted planes, as well as in curved                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60622 -                multiplanar reformats (Figure 1).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60624 -                 ..
P60625 -                To some degree, plaques can be classified based on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60626 -                their typical visual appearance.  The contrast-enhanced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60627 -                lumen can be easily identified as areas of high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60628 -                attenuation (approximately 200 to 500 Hounsfield units                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60629 -                [HU]).  Any discernible structure outside the lumen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60630 -                that is either calcified or has attenuation value less                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60631 -                than the lumen is considered to be part of the plaque.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60632 -                Based on the relative amount of calcified and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60633 -                noncalcified components, plaques are usually classified                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60634 -                into 1 of 3 categories: noncalcified plaque, calcified                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60635 -                plaque, or partially calcified plaque (sometimes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60636 -                referred to as ?mixed plaque?) (Figure 1).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60637 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60639 -                 ..
P60640 -            8.  Qualitative Plaque Characterization                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60641 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60642 -                A simple, qualitative plaque characterization scheme                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60643 -                has been used for clinical reporting of plaque types                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60644 -                on contrast-enhanced CTA (3). Each of the 17 coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60645 -                segments are visually assessed and classified on the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60646 -                basis on stenosis severity, and each plaque is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60647 -                classified as calcified, noncalcified, or partially                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60648 -                calcified. The reproducibility of this qualitative                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60649 -                assessment (Figure 1) has been shown to be good with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60650 -                both intraobserver and interobserver agreement in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60651 -                excess of 0.88 (Table 1) (4-5).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60653 -                 ..
P60654 -                The accuracy of this qualitative plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60655 -                characterization approach has been evaluated by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60656 -                Pundziute et al. (6), who showed that the 3 different                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60657 -                types of plaque had significantly different                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60658 -                composition as assessed by intravascular ultrasound                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60659 -                (IVUS) with radiofrequency backscatter analysis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60660 -                (IVUS/"virtual histology" [VH]). Importantly, they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60661 -                showed that 32% of partially calcified plaques in CT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60662 -                was characterized as thin-cap fibroatheroma (TCFA) by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60663 -                IVUS/VH.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60664 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60665 -                ...missing paragrpahs...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60666 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60668 -  ..
P60669 - CT Assess Arterialsclorsis Plaque Difficult Requires Equip Expertise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60670 - 
P60671 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60672 -            9.  Summary, Conclusions, And Future Directions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60673 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60674 -                Accurate detection of coronary atherosclerotic plaques                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60675 -                by CT remains difficult but can be performed with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60676 -                modern equipment, after careful patient selection and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60677 -                with sufficient expertise.  Attempts at plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60678 -                quantification and characterization have been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60679 -                successful, but further refinements regarding                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60680 -                reproducibility, accuracy, and ability to predict                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60681 -                future events are required.  With further improvements                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60682 -                in hardware and software, contrast-enhanced coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60683 -                CTA may become part of the armamentarium in the quest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60684 -                for the detection of the "vulnerable plaque" and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60685 -                "vulnerable patient" so that appropriate preventive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60686 -                measures can be instituted in a targeted fashion, at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60687 -                least partially based on the findings of coronary CTA.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60688 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60689 -                   [On 140515 letter to medical team reports visiting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60690 -                   San Francisco Medical Center Radiology Department on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60691 -                   doing coronary CTA assess regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60692 -                   atherosclerotic plaques resulting from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60693 -                   interventions, including CABG +4 on 091022, with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60694 -                   subsequent high levels of hyperlipedimeia (LDL 249),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60695 -                   followed by dramatic decline in LDL-P and rise of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60696 -                   HDL. ref SDS 59 YM41                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60697 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60699 -  ..
P60700 - Further Research found CT tests for arterslcorosis...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P60701 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60702 -            PubMed.gov                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60704 -             ..
P60705 -            US National Library of Medicine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60706 -            National Institute of Health (NIH)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60707 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60708 -              http://www.nlm.nih.gov/                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P60710 -             ..
P60711 -            JACC Cardiovasc Imaging                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60713 -             ..
P60714 -            Date.................... 2009 Nov 2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P60716 -             ..
P60717 -            Assessment of coronary plaque progression in coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60718 -            computed tomography angiography using a semiquantitative score.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60719 -            ------------------------------------------------------                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60720 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60721 -            By:  Lehman SJ, Schlett CL, Bamberg F, Lee H, Donnelly P,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60722 -            Shturman L, Kriegel MF, Brady TJ, Hoffmann U                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60723 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60724 -              http://www.ncbi.nlm.nih.gov/pubmed/19909929                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60726 -             ..
P60727 -            Author Information...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60729 -             ..
P60730 -            Cardiac MR PET CT Program, Massachusetts General Hospital                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60731 -            and Harvard Medical School, Boston, MA 02114, USA.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60732 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60733 -            1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60734 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60735 -                OBJECTIVES:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60737 -                 ..
P60738 -                We sought to describe the progression of coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60739 -                atherosclerotic plaque over time by computed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60740 -                tomography (CT) angiography stratified by plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60741 -                composition and its association with cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60742 -                risk profiles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60744 -                 ..
P60745 -            2.  BACKGROUND:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60746 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60747 -                Data on the progression of atherosclerosis stratified                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60748 -                by plaque composition with the use of noninvasive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60749 -                assessment by CT are limited and hampered by high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60750 -                measurement variability.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60752 -                 ..
P60753 -            3.  METHODS:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60754 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60755 -                This analysis included patients who presented with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60756 -                acute chest pain to the emergency department but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60757 -                initially showed no evidence of acute coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60758 -                syndromes.  All patients underwent contrast-enhanced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60759 -                64-slice CT at baseline and after 2 years with the use                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60760 -                of a similar protocol.  CT datasets were coregistered                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60761 -                and assessed for the presence of calcified and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60762 -                noncalcified plaque at 1 mm cross sections of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60763 -                proximal 40 mm of each major coronary artery.  Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60764 -                progression over time and its association with risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60765 -                factors were determined.  Measurement reproducibility                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60766 -                and correlation to plaque volume was performed in a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60767 -                subset of patients.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60769 -                 ..
P60770 -            4.  RESULTS:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60771 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60772 -                We included 69 patients (mean age 55 +/- 12 years, 59%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60773 -                male patients) and compared 8,311 coregistered cross                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60774 -                sections at baseline and follow-up.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60776 -                 ..
P60777 -                At baseline, any plaque, calcified plaque, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60778 -                noncalcified were detected in 12.5%, 10.1%, and 2.4% of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60779 -                cross sections per patient, respectively.  There was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60780 -                significant progression in the mean number of cross                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60781 -                sections containing any plaque (16.5 +/- 25.3 vs. 18.6                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60782 -                +/- 25.5, p = 0.01) and noncalcified plaque (3.1 +/-                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60783 -                5.8 vs. 4.4 +/- 7.0, p = 0.04) but not calcified plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60784 -                (13.3 +/- 23.1 vs. 14.2 +/- 22.0, p = 0.2).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P60786 -                 ..
P60787 -                In longitudinal regression analysis, the presence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60788 -                baseline plaque, number of cardiovascular risk factors,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60789 -                and smoking were independently associated with plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60790 -                progression after adjustment for age, sex, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60791 -                follow-up time interval.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P60793 -                 ..
P60794 -                The semiquantitative score based on cross sections                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60795 -                correlated closely with plaque volume progression (r =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60796 -                0.75, p < 0.0001) and demonstrated an excellent
P60797 -                intraobserver and interobserver agreement (kappa = 0.95                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P60798 -                and kappa = 0.93, respectively).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60800 -                 ..
P60801 -            5.  CONCLUSIONS:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60802 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60803 -                Coronary plaque burden of patients with acute chest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60804 -                pain significantly increases during the course of 2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60805 -                years.  Progression over time is dependent on plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60806 -                composition and cardiovascular risk profile.  Larger                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60807 -                studies are needed to confirm these results and to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P60808 -                determine the effect of medical treatment on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60809 -                progression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P60811 -  ..
P60812 - Images show CT image of artery with cross sections B1, B2, B3 taken                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60813 - at time T1.  Later at time T2, cross sections C1, C2 and C3 show                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P60814 - progression of arterial plaqque at C2 and C3.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P60816 -  ..
P60817 - Article "What We Can Learn From Tim Russert's Death" continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60819 -  ..
P60820 - This completes article above. ref SDS 0 N73K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P60821 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60822 -       12.  Don't allow yourself to be placed in the same position.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60823 -            Have your full risk factors evaluated and take those that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60824 -            can be changed seriously, embracing the idea of prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60825 -            and lifestyle change before its too late.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60827 -             ..
P60828 -       13.  Since Mr Russert was so committed to getting at the truth                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60829 -            and educating voters to have the facts necessary to make                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60830 -            good decisions, his death can be an opportunity to educate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P60831 -            us once more-- this time about heart disease and obesity.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P60833 -             ..
P60834 -       14.  Once again my condolences to his family, colleagues and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P60835 -            friends.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P60836 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60837 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60838 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60839 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P60840 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P609 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P703 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P70401 -  ..
P70402 - Exercise HDL Increase Aerobic Long Duration Lose Weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P70403 - HDL Increase Exercise Aerobic Long Duration Lose Weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P70404 - Aerobic Exercise Long Duration Lose Weight Increase HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P70405 - Weight HDL Increase Lose Weight Aerobic Long Duration Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70406 - 
P70407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70408 -        About.com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70409 -        Heart Health Center                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P70411 -         ..
P70412 -   10.  Raising Your HDL Levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P70413 -        Increasing the Good Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70414 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70415 -              http://heartdisease.about.com/cs/cholesterol/a/raiseHDL.htm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P70417 -         ..
P70418 -        Updated September 25, 2015                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70420 -         ..
P70421 -        By Richard N. Fogoros, MD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70422 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70423 -              http://heartdisease.about.com/bio/Richard-N-Fogoros-M-D-6616.htm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70424 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70425 -            Richard N. Fogoros, M.D. (DrRich) is a former professor of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70426 -            medicine, and a longtime practitioner, researcher and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70427 -            author in the fields of cardiology and cardiac                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P70428 -            electrophysiology. He currently makes his living as a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70429 -            consultant in research and development with biomedical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70430 -            Experience, and as a writer.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P70432 -             ..
P70433 -            Dr Rich practiced and taught clinical cardiology for 20                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70434 -            years, directing cardiac electrophysiology at the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P70435 -            University of Pittsburgh, and then at Allegheny General                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70436 -            Hospital in Pittsburgh. He was listed in Best Doctors in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P70437 -            America from its inception until he retired from practice.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70438 -            He has authored numerous scientific articles, book                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P70439 -            chapters, and books.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70440 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70442 -         ..
P70443 -        Date.................. Updated August 21, 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70445 -         ..
P70446 -        Reviewed by a board-certified health professional.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P70447 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70448 -              http://www.about.com/health/review.htm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P70449 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70450 -        1.  High levels of HDL cholesterol - often called "good"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70451 -            cholesterol - are associated with a reduced risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P70452 -            coronary artery disease (CAD).  It appears that HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P70453 -            particles "scour" the walls of blood vessels, cleaning out                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70454 -            excess cholesterol that otherwise might have been used to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70455 -            make the plaques that cause CAD.  The HDL cholesterol is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P70456 -            then carried to the liver, where it is processed into bile,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70457 -            and secreted into the intestines and out of the body.  So,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70458 -            when we measure a person's HDL cholesterol level, we seem                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70459 -            to be measuring how vigorously his or her blood vessels are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70460 -            being "scrubbed" free of cholesterol.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70462 -             ..
P70463 -            HDL levels below 40 mg/dL are associated with an increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70464 -            risk of CAD, even in people whose total cholesterol and LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70465 -            cholesterol levels are normal.  HDL levels between 40 and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70466 -            60 mg/dL are considered "normal," and do not very much                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70467 -            affect the risk of CAD one way or the other.  However, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70468 -            levels greater than 60 mg/dL are actually associated with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70469 -            reduced risk of heart disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P70470 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70472 -  ..
P70473 - HDL Lose Weight Aerobic Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70474 - HDL Increased with Drugs Caused Increased Cardiac Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P70475 - 
P70476 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70477 -        2.  In recent years it has become apparent that it is a gross                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70478 -            oversimplification to think of HDL cholesterol as always                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P70479 -            being "good." Some methods of increasing HDL levels, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70480 -            turns out, do not reduce cardiac risk.  Specifically,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70481 -            several randomized clinical trials with new drugs aimed at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70482 -            increasing HDL cholesterol have been a big disappointment.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70483 -            Indeed, when HDL was increased with some of these new                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70484 -            drugs, the cardiac risk was increased instead of decreased.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70485 -            (Needless to say, these drugs were never approved by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P70486 -            FDA.) So the HDL story is more complex than scientists                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70487 -            originally had hoped.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70489 -             ..
P70490 -        3.  Fortunately, it is still true that there are several                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70491 -            things we can all do to increase our HDL levels in a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70492 -            healthy way, and in a way that does appear to benefit our                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70493 -            risk of heart disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P70495 -             ..
P70496 -        4.  How can We Increase Our HDL Levels?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P70497 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70498 -            1.  Aerobic exercise.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70499 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70500 -                Many people don't like to hear it, but regular aerobic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70501 -                exercise (any exercise, such as walking, jogging or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70502 -                bike riding, that raises your heart rate for 20 to 30                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70503 -                minutes at a time) may be the most effective way to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70504 -                increase HDL levels.  Recent evidence suggests that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70505 -                duration of exercise, rather than the intensity, is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70506 -                more important factor in raising HDL choleserol.  But                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70507 -                any aerobic exercise helps.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P70509 -                 ..
P70510 -            2.  Lose weight.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P70511 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70512 -                Obesity results not only in increased LDL cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70513 -                but also in reduced HDL cholesterol.  If you are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70514 -                overweight, reducing your weight should increase your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70515 -                HDL levels.  This is especially important if your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70516 -                excess weight is stored in your abdominal area; your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P70517 -                waist-to-hip ratio is particularly important in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P70518 -                determining whether you ought to concentrate on weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70519 -                loss.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70521 -                 ..
P70522 -            3.  Stop smoking.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P70523 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70524 -                If you smoke, giving up tobacco will result in an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P70525 -                increase in HDL levels. (This is the only advantage I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70526 -                can think of that smokers have over non-smokers -- it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70527 -                gives them something else to do that will raise their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70528 -                HDL.)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P70530 -                 ..
P70531 -            4.  Cut out the trans fatty acids.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P70532 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70533 -                Trans fatty acids are currently present in many of your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70534 -                favorite prepared foods -- anything in which the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70535 -                nutrition label reads "partially hydrogenated vegetable                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70536 -                oils" -- so eliminating them from the diet is not a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70537 -                trivial task.  But trans fatty acids not only increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70538 -                LDL cholesterol levels, they also reduce HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P70539 -                cholesterol levels.  Removing them from your diet will                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P70540 -                almost certainly result in a measurable increase in HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P70541 -                levels.  Here's more about quick and easy review of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P70542 -                transfats and the heart.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P70543 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70544 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P70545 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P706 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P803 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P80401 -  ..
P80402 - Processed Food Chips Donuts High Trans Saturated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80403 - LDL Increase Saturated and Trans Saturated Acids                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80404 - Saturated and Trans Saturated Acids Increase LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80405 - Trans Saturated and Saturated Acids Increase LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80406 - 
P80407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80408 -                About.com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P80409 -                Heart Health Center                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80411 -                 ..
P80412 -                Trans Fatty Acids and the Heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80413 -                They're everywhere, and they may be worse than lard                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80414 -                
P80415 -                By Richard N. Fogoros, MD, ref SDS 0 V43O,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P80416 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80417 -                    http://heartdisease.about.com/cs/cholesterol/a/Transfat.htm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80419 -                 ..
P80420 -                Date.................. Updated October 18, 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P80421 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80422 -                1.  What Are Trans Fatty Acids (Trans Fats)?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P80423 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80424 -                    Natural foods (that is, unprocessed foods) contain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80425 -                    two main types of fatty acids - saturated and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P80426 -                    unsaturated.  Saturated fatty acids - which come                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80427 -                    from animal fats (meat, lard, dairy products) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80428 -                    tropical oils such as coconut and palm oils - can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80429 -                    raise your blood levels of LDL cholesterol.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P80430 -                    Unsaturated fats - which come from vegetable oils -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80431 -                    in general do not increase cholesterol levels, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80432 -                    may reduce them.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80434 -                     ..
P80435 -                2.  Trans fatty acids (trans fats) are a third form of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80436 -                    fatty acids. While trans fats do occur in tiny                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80437 -                    amounts in some foods (particularly foods from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80438 -                    animals), almost all the trans fats now in our                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80439 -                    diets come from an industrial process that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P80440 -                    partially hydrogenates (adds hydrogen to)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P80441 -                    unsaturated fatty acids.  Trans fats, then, are a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80442 -                    form of processed vegetable oils.  This means that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80443 -                    in our diets, trans fats are almost exclusively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80444 -                    found in the processed foods we eat.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P80446 -                     ..
P80447 -                3.  The advantage of trans fats to the food processing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80448 -                    industry is that partial hydrogenation solidifies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80449 -                    and stabilizes vegetable oils, which otherwise tend                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80450 -                    to turn rancid relatively quickly.  Because they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80451 -                    exist in solid form instead of liquid form, trans                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80452 -                    fats can be used as substitutes for saturated fats                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80453 -                    in food products that are meant to have a long                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80454 -                    shelf life.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P80456 -                     ..
P80457 -                4.  Trans fats were invented in the 1890s and began                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80458 -                    entering the food supply in the 1910s. However, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80459 -                    use of trans fats in food processing really took                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80460 -                    off in the 1970s and 1980s, when it was learned                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80461 -                    that saturated fats can be bad for your health.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80463 -                     ..
P80464 -                5.  Because trans fats were derived from the more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P80465 -                    healthy vegetable oils, it was assumed that they,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80466 -                    too, would be healthy food products.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P80468 -                     ..
P80469 -                6.  What Is Unhealthy About Trans Fats?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80470 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80471 -                    Unfortunately, as it turns out (and as we were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80472 -                    relatively slow to learn), trans fats increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80473 -                    total cholesterol levels and LDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80474 -                    levels; worse (and in contrast to saturated fats),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80475 -                    they reduce HDL cholesterol levels.  Trans fats                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80476 -                    also appear to interfere with the body's usage of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80477 -                    omega-3 fatty acids, which are important for heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80478 -                    health.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P80480 -                     ..
P80481 -                    In other words, trans fatty acids are bad for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P80482 -                    cardiovascular health.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P80484 -  ..
P80485 - Trans Acids Decrease HDL and Increase LDL Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80486 - 
P80487 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80488 -                7.  Which Is Worse - Saturated Fats or Trans Fats?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80489 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80490 -                    Both. Saturated fats and trans fatty acids are bad                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80491 -                    for you. Saturated fats are almost always found in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80492 -                    foods that also contain cholesterol, so saturated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80493 -                    fats offer a "one-two" punch to heart health.  On                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80494 -                    the other hand, trans fatty acids not only increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80495 -                    LDL cholesterol, they also decrease HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P80496 -                    cholesterol. While nobody can say yet definitively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80497 -                    which is worse, it does appear that both are bad.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80499 -  ..
P80500 - What study shows fatty acids affect health?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P80502 -  ..
P80503 - This representation appears conflicting with prior research indicating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80504 - eating food does not affect cholesterol, because it is excreted, per                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80505 - above. ref SDS 0 PQ81                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80507 -  ..
P80508 - Article "Trans Fatty Acids and the Heart" continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P80509 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80510 -                8.  Which Foods Contain Trans Fats?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80511 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80512 -                    Fortunately, today it is relatively easy to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P80513 -                    identify foods that contain substantial amounts of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80514 -                    trans fats. The easiest way is to check the food                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80515 -                    labels, since by law food manufacturers must now                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80516 -                    disclose how much trans fats they are putting into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80517 -                    their products.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80519 -                     ..
P80520 -                9.  Also, there are certain types of foods that are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80521 -                    very likely to contain trans fats. These include                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80522 -                    margarines. (The more solid the margarine, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P80523 -                    more the trans fatty acids. So, stick margarines                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80524 -                    contain the most, tub margarines less and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P80525 -                    semi-liquid margarines the least trans fats).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P80527 -                     ..
P80528 -               10.  Also, high-fat baked goods (especially doughnuts,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80529 -                    cookies, cakes, chips and crackers); most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P80530 -                    deep-fried foods; and any product that has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P80531 -                    "partially hydrogenated vegetable oils" contain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80532 -                    trans fats.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P80534 -                     ..
P80535 -               11.  What Are the Good Fats?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P80536 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80537 -                    Unsaturated vegetable oils from canola, peanuts,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80538 -                    olive, flax, corn, safflower and sunflower (as long                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P80539 -                    as they have not been subjected to the process of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P80540 -                    hydrogenation) are heart healthy. These oils                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80541 -                    contain monounsaturated or polyunsaturated fatty                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80542 -                    acids that can reduce total cholesterol and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P80543 -                    increase HDL cholesterol levels. These oils also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P80544 -                    contain the essential fatty acids - specific fatty                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80545 -                    acids necessary for life but which the body cannot                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P80546 -                    make itself - such as omega-3 and omega-6 fatty                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P80547 -                    acids.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P80548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80549 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80550 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80551 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P80552 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P806 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P903 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90401 -  ..
P90402 - Test LDL Small Dense Particle Size CAD Patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90403 - 
P90404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90405 - Another article researching cholesterol..                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90407 -        CDPHP Medical Messenger, May 2004                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P90409 -         ..
P90410 -   11.  Beyond Routine Cholesterol Testing:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P90411 -        The Role of LDL Particle Size Assessment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90412 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90413 -              http://www.centerforpreventivemedicine.com/04114med_messenger.pdf                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90414 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90415 -        by Paul E. Lemanski, MD,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90416 -        MS, director of the Center                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90417 -        for Preventive Medicine and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90418 -        Cardiovascular Health,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90419 -        Prime Care Physicians, P.C.,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90420 -        and assistant clinical professor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
P90421 -        of medicine at Albany                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90422 -        Medical College                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90423 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90424 -        1.  Cholesterol testing is an integral part of the global risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90425 -            assessment promoted by the National Cholesterol Education                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90426 -            Program (NCEP) ATP-3 guideline for clinicians.  For the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90427 -            majority of patients, such routine cholesterol testing and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90428 -            risk assessment will provide a fairly unequivocal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90429 -            determination of those needing pharmacological treatment.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90430 -            However, for borderline cases, clinicians have looked to a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90431 -            variety of new tests to further stratify risk.  One such                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90432 -            new test is LDL particle size.  The rationale for the use                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90433 -            of this test and suggestions for how clinical management                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90434 -            may be altered are reviewed below.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90436 -             ..
P90437 -        2.  The NCEP ATP-3 identifies LDL as the primary target of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90438 -            treatment not only because it has been shown to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90439 -            predictive of clinical events and angiographic disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90440 -            progression but also because of ease of measurement and low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90441 -            cost.  The LDL value reported to clinicians is the summed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90442 -            contribution in mg of LDL particles in a deciliter of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90443 -            plasma.  LDL particles are, however, heterogeneous in size,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90444 -            density, and composition.  A growing body of evidence                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90445 -            suggests that LDL particles that are small and dense are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90446 -            more atherogenic than those which are large and "fluffy."1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90447 -            Thus, two patients with the same LDL measurement in mg/dl                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90448 -            may have differing levels of cardiovascular risk depending                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90449 -            on the relative proportions of small, dense and large,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90450 -            fluffy particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90452 -             ..
P90453 -        3.  An increase in the proportion of small, dense LDL may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90454 -            increase risk for any given level of LDL.  This increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90455 -            risk may be due in part to increased deposition in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90456 -            sub-endothelial space where plaque forms.  It may be due                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90457 -            also to increased uptake by macrophages and increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90458 -            susceptibility to oxidation, both early steps in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
P90459 -            atherogenesis.  It may be due in part to decreased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90460 -            clearance because of reduced affinity for the LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90461 -            receptor2.  Observational and epidemiological studies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90462 -            suggest those having a predominance of small, dense                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90463 -            particles may have an increase in risk up to 300 percent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90464 -            greater than those having a predominance of large and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90465 -            fluffy LDL particles.  This observed increase in risk forms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90466 -            the basis of the rationale in using particle size as an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90467 -            adjunct to the standard proven means of risk assessment.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90469 -             ..
P90470 -        4.  Small, dense LDL may be measured directly by various means.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90471 -            Berkeley HeartLab, Inc.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90472 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90473 -                  http://www.bhlinc.com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P90475 -             ..
P90476 -            ...offers an LDL gradient gel electrophoresis; LipoScience,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90477 -            Inc.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90478 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90479 -                  http://www.lipoprofile.com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90480 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90481 -            ...offers a nuclear magnetic resonance (NMR) method;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90482 -            and Atherotec, Inc.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90483 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90484 -                  http://www.thevaptest.com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90486 -             ..
P90487 -            ...has their vertical auto profile (VAP) test.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P90489 -             ..
P90490 -            All measure small, dense LDL and thus may identify patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90491 -            as belonging to LDL subclass "phenotype B."  Phenotype B is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90492 -            terminology used to describe the LDL pattern in which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90493 -            small, dense LDL predominate.  It is seen more commonly in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90494 -            diabetic patients and those with established coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90495 -            artery disease (CAD).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90497 -             ..
P90498 -        5.  Small, dense LDL may also be identified in some situations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90499 -            by routine cholesterol testing.  Small, dense LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90500 -            are found in association with high triglycerides (TG) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90501 -            low HDL.  When TG, in a 12- hour fasting specimen, are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90502 -            increased in the serum, it is usually a result of increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90503 -            VLDL (very low density lipoprotein).  Under these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90504 -            conditions, TG are transferred from VLDL to LDL in exchange                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90505 -            for cholesterol ester by CETP (cholesterol ester transfer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90506 -            protein).  These TG enriched, cholesterol ester depleted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90507 -            LDL particles are then acted upon by hepatic lipase which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90508 -            cleaves out the TG leaving cholesterol ester depleted LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90509 -            particles.  The depleted LDL particles are physically                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90510 -            smaller and because of the resultant relative increase in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90511 -            protein also denser.  The association of TG with small,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90512 -            dense LDL suggests a possible means of establishing the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90513 -            presence of predominant small, dense LDL by use of TG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
P90514 -            measurement.  Indeed, such an association exists and proves                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90515 -            helpful in determining those for whom the test may best be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90516 -            applied.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90517 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90519 -  ..
P90520 - Triglycerides Lower Exercise Weight Loss Niacin Fibrates Increase LDL-P Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90521 - Weight Loss Exercise Niacin Fibrates Reduce Triglycerides Increase LDL-P Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90522 - Exercise Weight Loss Niacin Fibrates Reduce Triglycerides Increase LDL-P Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90523 - Niacin Exercise Weight Loss Fibrates Reduce Triglycerides Increase LDL-P Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90524 - 
P90525 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90526 -        6.  Austin has shown that those with TG above 140 have small,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90527 -            dense LDL and may be classified as LDL phenotype B on the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90528 -            basis of TG alone3.  Consequently, a separate test of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90529 -            particle size to identify individuals at increased risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90530 -            from small, dense LDL would be generally unnecessary for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90531 -            these individuals.  TG may also be used to track response                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90532 -            to treatment because the approaches which lower TG also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90533 -            convert small, dense LDL to large, fluffy, less atherogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90534 -            LDL.  Thus, weight loss, exercise, niacin, and fibrates                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90535 -            which, independently, have been shown to reduce TG, also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90536 -            convert small, dense LDL to larger, fluffy LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P90538 -             ..
P90539 -        7.  Individuals with TG below 70 do not have small, dense LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90540 -            It would not be necessary to measure LDL particle size in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90541 -            these individuals.  For individuals with TG between 70 and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90542 -            140, TG cannot be used to predict those with small, dense                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90543 -            LDL and a test of LDL particle size may be useful.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90544 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90546 -  ..
P90547 - Statins Do Not Change Particle Size Overlooks CVD Risk TG 70 - 40                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90548 - 
P90549 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90550 -        8.  As a class, statin drugs do not change particle size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90551 -            appreciably.  Thus, once patients achieve their NCEP LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90552 -            targets on statin treatment, if they also need                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P90553 -            pharmacological treatment of TG to achieve NCEP TG target                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90554 -            (<150), then a test of LDL particle size would not be
P90555 -            needed.  If the TG were between 70 and 140 and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90556 -            individual was a CAD risk equivalent, or had established                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90557 -            CAD and, more so, if he or she had progressing CAD,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90558 -            consideration may be given to measuring LDL particle size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90559 -            before the addition of niacin or fibric acid derivatives.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90560 -            The higher risk of combination therapy may suggest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
P90561 -            documenting the need for a second agent, especially if the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90562 -            lipid profile was already normalized by NCEP guideline                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90563 -            criteria.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90564 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90566 -  ..
P90567 - LDL Particle Size Measurement TG > 70 < 140 Assess CVD Risk
P90568 - CVD Risk Small Dense LDL Need Measurement LDL Particle Size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90569 - LDL-P Measurement Needed Assess CVD When TG > 70 < 140
P90570 - TG > 70 < 140 Direct Measurement LDL-P Size for Small Dense LDL
P90571 - 
P90572 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90573 -        9.  In summary, the measurement of LDL particle size may be of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90574 -            benefit for cardiovascular risk stratification as an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90575 -            adjunct to routine cholesterol testing and global risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90576 -            assessment for selected populations.  Identification of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
P90577 -            small, dense LDL may alter pharmacological management.  TG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90578 -            may be used to identify the majority of individuals with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90579 -            small, dense LDL.  Individuals with TG between 70 and 140                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90580 -            may require a direct measurement of particle size to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90581 -            establish the presence of small, dense LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90582 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90583 -               [...below on 131125 0005 article diagram shows why LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
P90584 -               particle size measurement essential to assess risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90585 -               arterialsclorsis caused by small, dense LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90586 -               penetrating the endothelial layer of an artery wall and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90587 -               collect to form plaque that progresses over time into a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90588 -               clot or blockage. ref SDS 0 1V4J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
P90590 -             ..
P90591 -       10.  Please see CDPHP resource coordination policy "LDL Particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90592 -            Size 1370/20.000404 for coverage guidelines for particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
P90593 -            size testing."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
P90594 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90595 -            1.  Gardner CD, Fortmann SP, Krauss RM.  Small low density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90596 -                lipoprotein particles are associated with the incidence                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90597 -                of coronary artery disease in men and women.  JAMA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90598 -                1996; 276:875-881.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90600 -                 ..
P90601 -            2.  Lamarche F, Tchernof A, Moorjani S, et al.  Small,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
P90602 -                dense low-density lipoprotein particles as a predictor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90603 -                of the risk of ischemic heart disease in men.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
P90604 -                Circulation. 1997;95:6975.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P90606 -                 ..
P90607 -            3.  Austin MA, King MC, Vranizan KM, Krauss RM.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
P90608 -                Atherogenic lipoprotein phenotype.  A proposed genetic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
P90609 -                marker for coronary heart disease risk.  Circulation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
P90610 -                1990;82:495506.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90612 -             ..
P90613 -       11.  Dr Lemanski may be reached at paul.lemanski@primecarepc.com                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
P90614 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90615 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90616 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90617 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P90618 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
P907 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0401 -  ..
PA0402 - Cholesterol Essential for Life Triglycerides Deliver Energy to Muscles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0403 - Triglycerides Deliver Energy to Muscles Cholesterol Essential for Life                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0404 - 
PA0405 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0406 - Another article researching cholesterol..                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0408 -        Thinking About Nutrition                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0410 -         ..
PA0411 -   12.  Why Cholesterol Misbehaves                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0412 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0413 -        by Doctor Banks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0414 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0415 -              http://www.thinkingaboutnutrition.com/2012/01/why-cholesterol-misbehaves/                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0417 -         ..
PA0418 -        Date....................... 23 January 2012                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0419 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0420 -        1.  "Cholesterol" has become perhaps the greatest health                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0421 -            villain of the past 2 decades.  However, it is really like                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0422 -            Robin Hood in many ways.  Like Robin Hood, cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0423 -            does many good things, but it can have a "bad" aspect in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0424 -            some cases.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0426 -             ..
PA0427 -        2.  As we discussed in the prior blog, cholesterol is an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0428 -            essential molecule in humans.  We have been given the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0429 -            impression that it is an evil invader that breaks into the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0430 -            body through diet.  This is an erroneous assumption that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0431 -            any well-versed physiologist will explain by reminding us                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0432 -            that about 80-85% of the circulating cholesterol in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0433 -            body is made in the liver and only 15-20% comes directly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0434 -            from food.  A large change in dietary cholesterol, let's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0435 -            say 50%, can only affect our circulating level by 7-9%.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0436 -            It is a much more meaningful objective to know why one's                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0437 -            body is choosing to make too much cholesterol and why                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0438 -            cholesterol, an essential part of human function,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PA0439 -            sometimes get in trouble.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0441 -  ..
PA0442 - Cholesterol aids digestion, memory, and immunity, reported in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0443 - connection with guidelines recently released by the American Heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0444 - Association AHA, shown in the record on 131112 1422. ref SDS 42 NF9H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0445 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0446 -               [...above on 131125 0005 reseach discovered Doctor Attia                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0447 -               maintains almost no cholesterol from eating affects body                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0448 -               cholesterol levels, because it is excreted, and that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0449 -               liver is the only source of cholesterol. ref SDS 0 PQ81                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0451 -             ..
PA0452 -        3.  The making too much issue requires examination of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0453 -            regulatory factors in cholesterol production.  Basically,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0454 -            when the things the body does with cholesterol need to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0455 -            done to a greater extent, a regulatory signal to the liver                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0456 -            occurs to increase production.  A common one is decline in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0457 -            hormone production such as by fatigued adrenal glands.  To                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0458 -            resolve this, the body increases the signal to produce                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0459 -            more "raw material" for production, cholesterol.  However,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0460 -            if the adrenal glands cannot do that because they are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0461 -            imbalanced, the cholesterol is not used and builds up.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0462 -            The task here is to figure out why the adrenal glands are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0463 -            fatigued and to revive "them".                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PA0464 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0465 -               [...above on 131125 0005 letter to medical team asks                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0466 -               what is causing HDL to fall and triglycerides to rise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0467 -               when it should be falling based on past patient history,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0468 -               and further asks if some systemic malady may be causing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0469 -               this conflict. ref SDS 0 UK82                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0471 -             ..
PA0472 -        4.  The second issue is the "misbehaving" aspect.  Not all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0473 -            cholesterol causes problems when it is too high in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0474 -            circulation.  LDL or "bad cholesterol" is not a single                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0475 -            type of cholesterol but rather a group with some members                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0476 -            who are not much of a problem and others who cause all of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0477 -            the trouble.  A little bit about how to read a panel of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0478 -            blood lipids helps to understand this.  The typical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0479 -            readings include;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PA0480 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0481 -            1.  Total cholesterol - just the sum weight of HDL (good                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0482 -                cholesterol) and the LDL group                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0484 -                 ..
PA0485 -            2.  HDL - good cholesterol, as it removes cholesterol from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0486 -                the circulation for disposal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0488 -                 ..
PA0489 -            3.  LDL - Delivers cholesterol from the liver to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0490 -                circulation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0492 -                 ..
PA0493 -            4.  VLDL - Helps to deliver cholesterol and triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0494 -                to the circulation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0496 -                 ..
PA0497 -            5.  Triglycerides - small fats produced from either dietary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0498 -                fats or carbohydrates/sugars                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0500 -  ..
PA0501 - Diagram Compare LDL TG Dense and LDL Cholesterol Fluffy Particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0502 - 
PA0503 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0504 -        5.  The LDL molecule is built around two different protein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0505 -            cores, apo B or apo A1.  The core around which a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0506 -            cholesterol particle is built is the primary determinant of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0507 -            how harmful or harmless the LDL molecule is.  Apo B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0508 -            molecules are very small and highly associated with causing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0509 -            vascular disease.  Apo A1 molecules are large and fluffy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0510 -            and much less likely to cause problems.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0511 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0513 -             ..
PA0514 -            Apo B type                 Single Apo B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0515 -            LDL Cholesterol         Cholesterol Particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0516 -                                        "Small Dense"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0517 -                B  B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0518 -              B  B   example dense          d d                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0519 -             B B  --------------------->   d B d                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0520 -                 B  B                       d d   \                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0521 -              B   B B                              \                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0522 -                B  B                               compare with large                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0523 -                                                 fluffy LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0524 -                                                          \                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0525 -                                                          /                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0526 -                                                         /
PA0527 -             ..
PA0528 -            Apo A Type                         Single Apo A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0529 -            LDL Cholesterol                 Cholesterol Particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0530 -                                               "Large Fluffy"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0531 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0532 -                     A                                 f f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PA0533 -               A    A A     A                        f     f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0534 -              A A    A     A A                     f   AAA   f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0535 -               A            A                     f   AAAAA   f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0536 -                        A                         f   AAAAA   f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0537 -                       A A ------------------->    f   AAA   f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0538 -                A       A    example fluffy          f     f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0539 -               A A                                     f f                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PA0540 -                A       A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0541 -                       A A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PA0542 -                        A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0543 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0545 -             ..
PA0546 -        6.  Any given persons total LDL pool is a mix of some apo B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0547 -            particles and some apo A1 particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0548 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0549 -                 LDL Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0550 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0551 -                         A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PA0552 -                        A A B   A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0553 -                         A   B A A  B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0554 -                            B   A      A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0555 -                        BB    B    B  A A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0556 -                            B B  A     A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0557 -                         A   B  A A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0558 -                        A A      A     A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0559 -                         A    A       A A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0560 -                             A A  BB   A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0561 -                              A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0562 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0564 -             ..
PA0565 -        7.  There is relatively weak correlation between simple LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0566 -            cholesterol levels and vascular disease risk such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0567 -            coronary artery disease.  The simple LDL cholesterol value                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0568 -            is only about 50-60% predictive of risk meaning that it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0569 -            tells us only slightly more than the toss of a coin.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0570 -            Knowing the LDL particle size is much more valuable.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0571 -            example below is of two persons both with the same LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0572 -            cholesterol readings of 120 mgs/dL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0574 -             ..
PA0575 -            Blood LDL ("Bad")               Blood LDL ("Bad")                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PA0576 -            Cholesterol Level               Cholesterol Level                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PA0577 -            120 mg/dL                       120 mg/dL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0579 -             ..
PA0580 -            Overall apo B Type               Overall apo A Type                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0581 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0582 -                 A                              A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0583 -                A1A B   A                      A1A     A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0584 -                 A   B A2A  B                   A     A2A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0585 -                    B   A    B              A      B   A      A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0586 -                B  B  B    B               A3A  B         B  A4A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0587 -                    B    A  B               A           A     A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0588 -               A  B  B  A4A                     A   B  A6A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PA0589 -              A3A     B  A   B                 A5A      A     A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0590 -               A    B     B                     A    A       A8A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0591 -                       B                            A7A   A   A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0592 -                                                     A   A9A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0593 -                                                          A
PA0594 -                  ..
PA0595 -                 Type A =  4                 Type A =  9                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0596 -                 Type B = 18                 Type B =  4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PA0598 -             ..
PA0599 -        8.  The 120 mgs/dL simply means that the total weight of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0600 -            cholesterol in a fixed volume of blood (dL or deciliter) is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0601 -            120 mgs.  As the diagram above shows, the same weight of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0602 -            cholesterol can be on fewer, larger apo A particles or on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0603 -            greater numbers of more small apo B particles.  Same total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0604 -            amount of LDL but very different risks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0606 -             ..
PA0607 -        9.  There is another type of "bad" cholesterol, VLDL.  This                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0608 -            type of LDL is always apo B or small particle LDL so when                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0609 -            it is elevated, it always suggest a more dangerous small                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0610 -            particle LDL pattern.  Sometimes a "cholesterol panel" will                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0611 -            be done which does not include VLDL.  Without it, one only                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0612 -            knows half the story of risk.  The true total "bad"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0613 -            cholesterol is LDL + VLDL which is called "non-HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0614 -            cholesterol".  This is a better indicator of positive or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0615 -            negative effects of therapy than is the LDL reading alone.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0616 -            Making more VLDL will usually decrease the levels of HDL or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0617 -            good cholesterol so it is like a double whammy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0619 -             ..
PA0620 -       10.  All of this can be sorted out with a more comprehensive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0621 -            test that measures the number and type of LDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0622 -            called a VAP profile.  This test will show the majority                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0623 -            pattern of LDL particles (large, fluffy, or small and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0624 -            dense).  It is usually shown on a bar graph as seen below:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0626 -               ..
PA0627 -              [_______________] [_______] [_______________________]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0628 -              Pattern B         Pattern                   Pattern A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0629 -              Small Dense LDL     A/B     Large Byoyant LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0630 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0632 -             ..
PA0633 -       11.  Dietary changes may produce only a small drop in "LDL" but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0634 -            VLDL may drop dramatically causing a very good decrease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PA0635 -            total non-HDL cholesterol.  Without looking at total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0636 -            non-HDL or "total bad cholesterol" it is hard to tell if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0637 -            risk is improved or worsened.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0638 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0640 -  ..
PA0641 - Genetic Variability Tolerates Different Dietary Content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0642 - Carbohydrate/sugar Diet Cause Dangerous Small Dense LDL Particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0643 - 
PA0644 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0645 -       12.  Although our tendency to make larger or smaller particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0646 -            is partly set based on genetics, it is also partly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PA0647 -            determined by lifestyle and diet.  Eating a high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0648 -            carbohydrate/sugar diet will cause a shift towards smaller,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0649 -            more dangerous LDL particles.  This is typical of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0650 -            standard "low fat" diet.  Fat calories are replaced with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0651 -            carbohydrates which cause a shift towards more dangerous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0652 -            particles.  There is no "one diet fits all" because                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0653 -            different people by the genetic type tolerate different                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PA0654 -            nutrient diet contents.  Looking at the different factors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0655 -            in a cholesterol test will help to guide individual                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PA0656 -            specific therapy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PA0657 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0658 -                [...above on 131125 0005 patient Internet report that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PA0659 -                low-carb diet supports raising HDL, lowering                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PA0660 -                triglycerides and lowering LDL-P. ref SDS 0 5P5N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0662 -                 ..
PA0663 -                [...above on 131125 0005 article "Doc's Opinion" by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0664 -                Doctor Axel F Sigurdsson recommends low-carb diet for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0665 -                lowering LDL-P. ref SDS 0 QP9F and ref SDS 0 J56H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0667 -             ..
PA0668 -       13.  There are also different nutrients that can be supplemented                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0669 -            that increase particle size, that lower VLDL and total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0670 -            non-HDL and that raise HDL.  Once one's complete picture is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PA0671 -            understood a much more focused nutritional supplement                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PA0672 -            program can be used which will produce better results.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PA0674 -             ..
PA0675 -       14.  This was a lot said to understand "why is my cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PA0676 -            misbehaving" but only looking at one piece of the problem                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0677 -            can often lead to either inadequate realization of risks,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PA0678 -            or over treatment.  It is worth a careful look!                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PA0679 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0680 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0681 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA0682 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PA07 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PB03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PB0401 -  ..
PB0402 - Exercise Lowers Triglycerides Strengthens Cardiovascular Function                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PB0403 - 
PB0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0405 -   13.  Does Exercise Lower Triglyceride Levels?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0407 -        Kristie Leong M.D                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PB0408 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0409 -              http://voices.yahoo.com/does-exercise-lower-triglyceride-levels-10297231.html                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PB0410 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0411 -              http://rustycab.com/does-exercise-lower-triglyceride-levels/                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PB0413 -         ..
PB0414 -        Nov 4, 2011                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PB0415 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0416 -        1.  A high triglyceride level is a risk factor for heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0417 -            disease in the same way an elevated cholesterol is.  A high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PB0418 -            triglyceride level is not only unhealthy for your heart, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PB0419 -            increases the risk of stroke and pancreatitis, an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PB0420 -            inflammatory condition of the pancreas.  Studies show that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0421 -            even "normal" triglyceride levels of arouind 150 mg/dl. are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PB0422 -            a risk factor for heart disease and that people should aim                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0423 -            for levels of 100 mg/dl. or less.  If you have an elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0424 -            triglyceride level, most doctors recommend altering your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0425 -            diet - but what about exercise and triglycerides?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PB0427 -             ..
PB0428 -        2.  Does Exercise Lower Triglycerides?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PB0429 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0430 -            Exercise is effective for lowering triglyceride levels as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0431 -            long as you do it consistently.  Triglycerides are simply                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0432 -            fats that circulate in the blood bound to particles called                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0433 -            lipoproteins that also carry cholesterol.  As they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PB0434 -            circulate, tissues pick up some of these triglycerides to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0435 -            use for energy or store them to use as fuel later.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PB0436 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0437 -                [...above on 131125, another source explains exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PB0438 -                lowers LDL-P. ref SDS 0 QP9F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PB0439 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0441 -             ..
PB0442 -        3.  During moderate-intensity exercise of a longer duration,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0443 -            the body burns mostly fat as fuel, so more triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0444 -            are broken down during aerobic exercise and used as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PB0445 -            energy, which reduces the amount in your bloodstream.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PB0447 -             ..
PB0448 -        4.  To lower triglycerides through exercise, exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PB0449 -            aerobically for at least twenty minutes per session,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0450 -            preferably thirty or more minutes. For the first minutes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0451 -            of exercise, your body burns mostly glycogen, but if you                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0452 -            exercise longer, your body switches to burning mostly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PB0453 -            triglycerides as fuel - if you keep the pace moderate.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PB0455 -             ..
PB0456 -        5.  Exercise and Triglycerides: Morning Exercise May Be Better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0457 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0458 -            A small study carried out at the University of Colorado                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PB0459 -            Health Sciences Center, found that exercising first thing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0460 -            in the morning may have more of an impact on triglyceride                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0461 -            levels than working out later in the day. Keep your                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PB0462 -            exercise shoes by the bed, and do at least a twenty minute                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0463 -            workout as soon as you wake up to get the most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PB0465 -             ..
PB0466 -        6.  If you're a "slow-riser" and can't face exercise before the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PB0467 -            noon hour, don't let it deter you.  Consistency is key -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0468 -            and as long as you do it regularly, you should get modest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0469 -            triglyceride-lowering benefits.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PB0471 -             ..
PB0472 -        7.  Does Exercise Lower Triglycerides: The Bottom Line?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PB0473 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0474 -            Doing aerobic exercise at a moderate-intensity for at least                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PB0475 -            20 minutes per session can help you lower your triglyceride                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PB0476 -            level.  More good news.  It also lowers your risk of heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0477 -            disease independently of your triglyceride level.  If you                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PB0478 -            have an elevated triglyceride level, get out your exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0479 -            shoes - and put them to good use.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PB0481 -             ..
PB0482 -        8.  References                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PB0483 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0484 -            DOC NEWS January 2006 vol. 3 no. 19                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PB0486 -             ..
PB0487 -            University of Maryland Medical Center. "Study Finds                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PB0488 -            "Normal" Triglyceride Levels are Tricky"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PB0489 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0490 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0491 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0492 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB0493 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PB05 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PC03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PC0401 -  ..
PC0402 - Triglycerides Eggs Decrease Improve Control Arterialsclorosis Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PC0403 - HDL Eggs Increase Quantity Quality Control Arterialsclorosis Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PC0404 - Arterialsclorosis CVD Risk Eggs Increase HDL Function Triglycerides Lower                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PC0405 - Eggs HDL Rise Triglycerides Decrease Improve Control CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PC0406 - 
PC0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0408 -        Pubmed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PC0409 -        US National Library of Medicine National Institutes of Health                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0411 -         ..
PC0412 -        Lipids. 2013 Jun;48(6):557-67. doi: 10.1007/s11745-013-3780-8.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PC0414 -         ..
PC0415 -   14.  Egg consumption modulates HDL lipid composition and increases                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0416 -        the cholesterol-accepting capacity of serum in metabolic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0417 -        syndrome.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PC0418 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0419 -              http://www.ncbi.nlm.nih.gov/pubmed/23494579                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PC0421 -         ..
PC0422 -        Andersen CJ, Blesso CN, Lee J, Barona J, Shah D, Thomas MJ,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PC0423 -        Fernandez ML.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0425 -         ..
PC0426 -        Author information                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PC0428 -         ..
PC0429 -        Epub 2013 Mar 15.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PC0431 -         ..
PC0432 -        Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0433 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0434 -        1.  We recently demonstrated that daily whole egg consumption                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0435 -            during moderate carbohydrate restriction leads to greater                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0436 -            increases in plasma HDL-cholesterol (HDL-C) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PC0437 -            improvements in HDL profiles in metabolic syndrome (MetS)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0438 -            when compared to intake of a yolk-free egg substitute.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PC0440 -             ..
PC0441 -        2.  We further investigated the effects of this intervention on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0442 -            HDL composition and function, hypothesizing that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0443 -            phospholipid species present in egg yolk modulate HDL lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0444 -            composition to increase the cholesterol-accepting capacity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PC0445 -            of subject serum.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PC0447 -             ..
PC0448 -        3.  Men and women classified with MetS were randomly assigned                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0449 -            to consume either three whole eggs (EGG, n = 20) per day or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0450 -            the equivalent amount of egg substitute (SUB, n = 17)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PC0451 -            throughout a 12-week moderate carbohydrate-restricted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PC0452 -            (25-30 % of energy) diet.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0454 -             ..
PC0455 -        4.  Relative to other HDL lipids, HDL-cholesteryl ester content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0456 -            increased in all subjects, with greater increases in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PC0457 -            SUB group.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PC0459 -             ..
PC0460 -        5.  Further, HDL-triacylglycerol content was reduced in EGG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PC0461 -            group subjects with normal baseline plasma HDL-C, resulting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0462 -            in increases in HDL-CE/TAG ratios in both groups.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PC0464 -             ..
PC0465 -        6.  Phospholipid analysis by mass spectrometry revealed that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PC0466 -            HDL became enriched in phosphatidylethanolamine in the EGG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PC0467 -            group, and that EGG group HDL better reflected                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PC0468 -            sphingomyelin species present in the whole egg product at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PC0469 -            week 12 compared to baseline.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PC0471 -             ..
PC0472 -        7.  Further, macrophage cholesterol efflux to EGG subject serum                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0473 -            increased from baseline to week 12, whereas no changes were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0474 -            observed in the SUB group.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PC0476 -             ..
PC0477 -        8.  Together, these findings suggest that daily egg consumption                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PC0478 -            promotes favorable shifts in HDL lipid composition and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PC0479 -            function beyond increasing plasma HDL-C in MetS.  PMID:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PC0480 -            23494579 [PubMed - indexed for MEDLINE] PMCID:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PC0481 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0482 -                [...above on 131125 clinical study found consuming 750                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PC0483 -                ml orange juice per day raised HDL 21%. ref SDS 0 R48K                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PC0485 -             ..
PC0486 -            PMC3869568 [Available on 2014/6/1]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PC0487 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0488 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0489 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0490 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC0491 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PC05 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PD03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0401 -  ..
PD0402 - LDL Pattern A > 250 AN LDL Pattern B < 250 AN Penetrate Endothelial Lining Artery
PD0403 - 
PD0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0405 -        Journal of Lipid Research Volume 31, 1990                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0407 -   15.  Differences in carbohydrate content of low density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0408 -        lipoproteins associated with low density lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PD0409 -        subclass patterns                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PD0411 -         ..
PD0412 -        Michael La Belle' and Ronald M. Krauss                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0413 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0414 -              http://www.jlr.org/content/31/9/1577.full.pdf                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0416 -         ..
PD0417 -        Donner Laboratory, University of California, and Molecular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0418 -        Medicine Research Program,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0420 -         ..
PD0421 -        Research Medicine and Radiation Biophysics Division, Lawrence                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0422 -        Berkeley Laboratory, 1 Cyclotron Road, Berkeley, CA 94720                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0424 -         ..
PD0425 -        Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0427 -         ..
PD0428 -        The neutral carbohydrate content of both the protein (apoB) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0429 -        lipid fractions of low density lipoproteins (LDL) from subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0430 -        with a predominance of small, dense LDL (sub- class pattern B)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0431 -        was found to be lower than in subjects with larger LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0432 -        (subclass pattern A): 45 * 12 versus 64 * 13 mg/g apoLDL, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0433 -        58 * 8 versus 71 * 8 mg/g apoLDL (P<0.0005 for both).  Sialic
PD0434 -        acid content of LDL lipids, but not apoB, was also reduced in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0435 -        subclass pattern B.  ApoB and glycolipid carbo- hydrate content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0436 -        of total LDL and LDL density subfractions declined with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0437 -        increasing LDL density and decreasing particle diameter.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0438 -        Moreover, in LDL subfractions from pattern B subjects,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0439 -        carbohydrate content of LDL apoB, but not LDL glycolipid, was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0440 -        significantly lower in comparison with particles of simiiar                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0441 -        size from pattern A subjects.  Thus, in LDL subclass pattern B,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0442 -        reductions in LDL carbohydrate content are associated both with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0443 -        reduced concentrations of larger carbohydrate-enriched LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0444 -        subclasses, and with reduced glycosylation of apoB in all LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0445 -        particles.  LDL glycolipids may vary with overall lipid con-                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0446 -        tent of LDL particles, but variation in apoB glycosylation may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0447 -        indicate differences in pathways for LDL production, and re-                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0448 -        duced apoB glycosylation may reflect the altered metabolic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0449 -        state responsible for LDL subclass pattern B.-La Belle, M., and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0450 -        R M Krause.  Differences in carbohydrate content of low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0451 -        density lipoproteins associated with low density lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0452 -        subclass patterns.  J Lipid Rcs. 1990. 31: 1577-1588.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0454 -         ..
PD0455 -        Abbreviations:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0456 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0457 -        1.  LDL, low density lipoprotein;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PD0458 -        2.  apoB, apolipoprotein B;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0459 -        3.  VLDL, very low density lipoprotein;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0460 -        4.  IDL, intermediate density lipoprotein;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0461 -        5.  HDL, high density lipoprotein;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0462 -        6.  apoLDL, LDL protein;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0463 -        7.  FH, familial hypercholesterolemia;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0464 -        8.  kD, kdodalton;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0465 -        9.  SDS, sodium dodecyl sulfate;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PD0466 -       10.  WGA, wheat germ agglutinin;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0467 -       11.  VNTR, variable number of terminal repeats;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0468 -       12.  ER, endoplasmic reticulum;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0469 -       13.  LCP, lipoprotein-complexing proteoglycan;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0470 -       14.  BSA, bovine serum albumin.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0472 -         ..
PD0473 -        Low density lipoproteins (LDL) in humans function as the major                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0474 -        carriers of plasma cholesterol and levels of LDL cholesterol in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0475 -        the plasma have been correlated with the risk of heart disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0476 -        (1, 2).  In addition, a positive correla- tion has been found                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0477 -        between coronary heart disease and high levels of plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0478 -        triglyceride, very low density lipo- proteins (VLDL), and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0479 -        intermediate density lipoproteins (IDL) (3-5), while levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0480 -        high density lipoprotein (HDL) choleste disease (6, 7).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0482 -         ..
PD0483 -        Earlier work has shown heterogeneity of LDL particle size,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0484 -        density, and composition (8-16) and the existence of distinct                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0485 -        subclasses of LDL that can be identified by ultra- centrifugal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0486 -        and gel electrophoretic techniques (13-16).  Analysis of LDL by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0487 -        gradient gel electrophoresis showed that LDL from most subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0488 -        falls into one of two distinct LDL subclass patterns, A or B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0489 -        (16, 17).  LDL subclass pattern A is characterized by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0490 -        presence of a major LDL with a large diameter (usually greater                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0491 -        than 255 A) and a secondary LDL peak of smaller diameter, while                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0492 -        LDL subclass pattern B has a major LDL peak of smaller                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0493 -        diameter, usually less than 255 A in diameter, and a secondary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0494 -        LDL peak of larger diameter than the major peak (Fig. 1).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0495 -        Complex segregation analysis has shown that these LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0496 -        patterns are influenced by a common allele at a single genetic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0497 -        locus (18).  The pattern B-associated allele has a population                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0498 -        frequency of approximately 25% and is dominant, but with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0499 -        reduced penetrance in young males (<20 yr) and premenopausal
PD0500 -        women (17).  Individuals with LDL subclass pattern B have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0501 -        relatively increased levels of triglyceride, VLDL, and IDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0502 -        decreased levels of HDL cholesterol (16-18), a profile that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0503 -        would predict an increased risk of atherosclerosis.  A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0504 -        subsequent study of LDL subclass patterns versus risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0505 -        myocardial infarction found that individuals with LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0506 -        pattern B have up to a threefold in- crease in risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0507 -        myocardial infarction (19).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0508 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0509 -        ********************                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PD0510 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0511 -                 269 A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0512 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0513 -                   |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0514 -                  | |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0515 -                  | |                       251 A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0516 -                  / \                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0517 -                  | |                         |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0518 -                  | |                        / |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0519 -                  | |  263 A                 | |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0520 -                  /  \               264 A   | |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0521 -                 /    \/\                  /\/ |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0522 -                .        .                /    \                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0523 -               .           .             .      .                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0524 -             .               . .       .          . . ...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PD0526 -         ..
PD0527 -        Fig I.  Densitometric scans of plasma low density lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0528 -        particles electrophoresed under nondenaturing conditions on 2 %                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0529 -        to 16 % gradient gel and stained with Oil Red 0.  Left: scan of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0530 -        LDL subclass pattern A, which is characterized by a felatively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0531 -        large major LDL peak (269 A) and a smaller diameter (263 A)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0532 -        secondary peak.  Right: scan of LDL subclass pattern B,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0533 -        characterized by a. relatively small major LDL peak (251 A) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0534 -        a larger diameter (264 A) secondary LDL peak                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0535 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0536 -        **********************                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0538 -         ..
PD0539 -        The smaller LDL species that predominate in LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0540 -        pattern B have also been shown to have a higher buoyant density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0541 -        and relatively lower 1ipid:protein ratio than the larger LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0542 -        that predominate in subclass pattern A (15).  The question                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0543 -        arises as to whether there are other structural differences                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0544 -        between the LDL found in subclass pattern A and B that may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0545 -        relate to the genetic basis of the LDL subclass patterns and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0546 -        that might contribute to differences in coronary disease risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0547 -        associated with these patterns.  Low density lipoproteins are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0548 -        complex macromo- lecules consisting of a core of esterified                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0549 -        cholesterol (with a small amount of triglyceride) surrounded by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0550 -        a layer of more polar lipids (free cholesterol and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0551 -        phospholipids) and a single large ( = 550 kD) glycoprotein,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0552 -        apolipoprotein B (apoB).  The amount of carbohydrate present on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0553 -        apoB has been reported to range from 4% to 10% (40 to 100 mg/g                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0554 -        apoB) by weight (20-28).  At least 50% of the carbohy- drate on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0555 -        apoB is present in the form of either of two types of N-linked                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0556 -        carbohydrate chains: a high-mannose olig- osaccharide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0557 -        containing six mannose and two N-acetyl- glucosamine residues                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0558 -        and a complex-type oligosaccharide containing two sialic acid,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0559 -        two galactose, five mannose, and three N-acetylglucosamine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0560 -        residues (22).  In addition, other investigators report the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0561 -        presence of high-mannose N-linked oligosaccharides composed of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0562 -        six to nine man- nose residues and one N-acetylglucosamine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0563 -        residue (27).  The function of the carbohydrate moiety of apoB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0564 -        in VLDL and LDL is unknown.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0566 -         ..
PD0567 -        In this study we report on differences in the carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0568 -        content of the LDL isolated from subjects with LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0569 -        pattern A or B.  The results demonstrate that LDL from subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0570 -        with subclass pattern B have sig- nificantly less neutral                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0571 -        carbohydrate and sialic acid than LDL from subjects with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0572 -        subclass pattern A and that this difference is due to reduced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0573 -        carbohydrate in both the lipid and protein fractions of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0574 -        pattern B LDL particles.  In addition, there is a linear                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0575 -        relationship between LDL carbohydrate content and size of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0576 -        major LDL peak.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0578 -         ..
PD0579 -        Table 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0580 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0581 -          Comparison of age, sex, B.M.I. (body mass index), plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0582 -          triglyceride levels, cholesterol levels, and diameter of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0583 -          main LDL of subjects in LDL subclass pattem A versus subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0584 -          in LDL subclass pattem B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0585 -        ..
PD0586 -                                                         Particle
PD0587 -        Pattern  Age  Sex BMI   Triglycerides Total  HDL  LDL  Diameter                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0588 -                               2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0589 -                          kg/cm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0590 -        A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PD0591 -        n = 31    21   M  24.8        97       136    46   71     263                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0592 -                  22   M  23.6        66       155    52   90     258                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0593 -                  26   M  22.0        85       174    69   88     264                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0594 -                  35   M  25.6       120       220    37  159     267                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0595 -                  37   M  20.6        50       139    61   68     263                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0596 -                  37   M  23.0        76       201    63  123     265                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0597 -                  39   M  21.3        95       206    51  136     265                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0598 -                  43   M  22.2        62       188    36  140     267                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0599 -                  45   M  22.0        47       137    47   81     275                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0600 -                  47   M  22.2        51       135    39   86     257                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0601 -                  47   M  24.0       137       194    41  126     261                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0602 -                  51   M  24.4        80       153    70   67     264                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0603 -                  57   M  20.1       132       237    61  150     262                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0604 -                  64   M  27.9        99       176    61   95     267                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0605 -                  72   M  25.4        86       183    48  118     266                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0606 -                  20   F  20.7        93       145    61   65     276                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0607 -                  24   F  20.7        47       186    72  105     275                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0608 -                  26   F  21.8        29       190    72  112     274                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0609 -                  28   F  19.0        50       184    77   97     270                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0610 -                  29   F  25.7        75       166    69   82     272                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0611 -                  29   F  22.5        87       196    77  102     265                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0612 -                  30   F  21.3        37       198    95   96     271                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0613 -                  34   F  20.4        70       248    86  148     272                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0614 -                  35   F  19.8        53       154    66   77     272                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0615 -                  35   F  20.6        92       199    69  112     262                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0616 -                  40   F  25.6        95       174    72   83     272                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0617 -                  42   F  23.3        77       235    93  127     276                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0618 -                  43   F  21.1        78       211    64  131     278                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0619 -                  44   F  21.9        76       150    36   99     262                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0620 -                  55   F  29.1        65       207    60  134     272                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0621 -                  68   F  20.0       145       253    78  146     261
PD0622 -         ..
PD0623 -        Average   40      22.7        79       185    62  107     267                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0624 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0626 -         ..
PD0627 -        B         31   M  28.4       210       217    37  138     247                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0628 -        n = 34    35   M  23.6       151       221    31  160     251                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0629 -                  35   M  23.7       179       193    29  128     248                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0630 -                  36   M  23.7        99       241    39  182     250                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0631 -                  36   M  22.0        88       146    28  100     252                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0632 -                  37   M  25.1        74       180    47  118     259                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0633 -                  39   M  21.6       170       198    44  120     248                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0634 -                  40   M  35.9       223       175    24  106     245                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0635 -                  41   M  21.0       286       222    27  138     245                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0636 -                  42   M  26.3       216       251    27  181     248                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0637 -                  43   M  27.0       396       200    37   84     246                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0638 -                  44   M  37.4       133       211    34  150     252                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0639 -                  44   M  27.6       275       288    36  197     246                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0640 -                  46   M  29.6       212       205    34  129     245                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0641 -                  46   M  23.7       263       199    35  111     242                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0642 -                  49   M  24.3       237       197    32  118     244                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0643 -                  49   M  22.7       316       294    33  198     248                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0644 -                  50   M  24.3       269       225    32  139     249                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0645 -                  51   M  27.3       104       190    49  120     259                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0646 -                  54   M  26.4       128       219    38  155     246                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0647 -                  54   M  28.3       365       190    39   78     262                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0648 -                  55   M  23.0       222       220    34  142     245                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0649 -                  56   M  23.8       187       243    52  154     249                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0650 -                  57   M  29.3       185       201    31  133     248                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0651 -                  60   M  29.6       251       173    31   92     254                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0652 -                  61   M  28.2       124       222    44  153     260                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0653 -                  68   M  32.2       217       156    22   91     242                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0654 -                  23   F  20.9       129       216    39  151     249                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0655 -                  51   F  27.3       107       261    57  183     249                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0656 -                  65   F  25.2       161       241    37  172     259                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0657 -                  67   F  25.7       180       257    41  180     258                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0658 -                  72   F  25.6       145       258    37  192     250                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0659 -                  82   F  20.7       120       240    63  153     262                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0660 -                  84   F  22.1       436       258    35  136     243
PD0661 -         ..
PD0662 -        Average   50      26         202       217    37  141     250                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0663 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0665 -         ..
PD0666 -        [...omit materials and methods...]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0668 -         ..
PD0669 -        Results                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0671 -         ..
PD0672 -        Table 1 presents the clinical characteristics of the study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0673 -        subjects, their plasma lipid levels and the diameters of their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0674 -        predominant LDL peak as determined by nondenaturing gradient                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0675 -        gel electrophoresis.  As a group, the subjects with LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0676 -        subclass pattern B were older and had greater body mass than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0677 -        the subjects with pattern A.  Triglyceride, total cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0678 -        and LDL cholesterol were all significantly greater (P< 0.0005)
PD0679 -        and HDL cholesterol levels were significantly lower (P<0.0005)
PD0680 -        in the LDL subclass pattern B group than in the pattern A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0681 -        group.  These differences, as well as differences in particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0682 -        size of the predominant LDL species, are similar to those                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0683 -        reported previously (17, 19).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0685 -         ..
PD0686 -        Determination of the neutral carbohydrate content of isolated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0687 -        LDL samples (Table 2) revealed significantly lower levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0688 -        total LDL carbohydrate in pattern B than in pattern A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0689 -        (P<O.O005).  This difference was dye to significantly lower
PD0690 -        levels of carbohydrate in both the glycolipid (P<O.O005) and
PD0691 -        apoprotein (P<0.0005) components of LDL in pattern B subjects.
PD0693 -         ..
PD0694 -        Table 2 also shows that sialic acid content of total LDL was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0695 -        significantly lower in subjects with LDL subclass pattern B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0696 -        than in subjects with pattern A, by approximately one mole per                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0697 -        mole of LDL.  However, sialic acid content of apoLDL,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0698 -        determined in subgroups of 12 subjects each with LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0699 -        patterns A and B, was similar in the two groups: 3.2 f 0.7                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0700 -        versus 3.3 * 0.8 mol/mol apoLDL.  Thus, the difference in total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0701 -        LDL sialic content between LDL subclass patterns A and B is due                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0702 -        to the lower glycolipid content of LDL in pattern B subjects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0703 -        Comparison of LDL electrophoretic mobility on agarose before                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0704 -        and after exposure to neuraminidase in 10 pattern A and 9                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0705 -        pattern B subjects showed a significantly greater reduction in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0706 -        pattern A versus pattern B mobility (54 * 4% vs 45 * 4%,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0707 -        P<O.Ol), consistent with the presence of less sialic acid in
PD0708 -        glycolipids from pattern B LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0710 -         ..
PD0711 -        To determine whether the increased carbohydrate content of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0712 -        apoLDL in subclass pattern A was due to the presence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0713 -        glycolipoproteins other than apoB-100, such as apoE (43), apoD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0714 -        (44), or apoC-I11 (45), nitrocellulose blots of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0715 -        electrophoretically separated apoLDL samples pooled from 12                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0716 -        subjects each with LDL subclass pattern A and B were stained                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0717 -        for protein or probed for glycoprotein with the biotinylated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0718 -        lectin WGA (Fig. 2).  In both samples, only a single apoB-100                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0719 -        band was visualized by each procedure.  Since WGA binds                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0720 -        specifically to Nacetyl- D-glucosamine and sialic acid (42),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0721 -        and N-acetyl- D-glucosamine is part of the core structure of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0722 -        both high mannose and complex N-linked carbohydrate chains,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0723 -        this result argues against the presence of significant amounts                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0724 -        of glycoproteins other than apoB-100 in the LDL preparations.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0726 -         ..
PD0727 -        Individual values for LDL carbohydrate measurements are shown                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0728 -        in Fig. 3 in relation to the particle diameter of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0729 -        predominant LDL subspecies on gradient gel electrophoresis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0730 -        Significant positive correlations with peak LDL diameter were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0731 -        observed for total LDL carbohydrate, LDL glycolipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PD0732 -        carbohydrate, and apoLDL carbohydrate (Fig. 3A-C), consistent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0733 -        with the mean differences between subjects with predominantly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0734 -        smaller and larger LDL.  Correlations of carbohydrate content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0735 -        with peak LDL particle diameter within the phenotypes were not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0736 -        statistically significant.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0738 -         ..
PD0739 -        In a subject with familial hypercholesterolemia, the peak LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0740 -        particle diameter was 274 (LDL subclass pattern A) and LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0741 -        carbohydrate content was 170 mg/g apoLDL (105 mg/g apoLDL in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0742 -        protein and 65 mg/g apoLDL in lipids).  In addition, sialic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0743 -        acid content was 4.9 0.3 mol/mol LDL.  These findings were all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0744 -        consistent with those of normolipidemic subjects with LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0745 -        subclass pattern A.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PD0747 -         ..
PD0748 -        In view of the differences in plasma lipid levels as well as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0749 -        mean age and body mass index between subjects with differing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0750 -        LDL subclass patterns, relationships were sought between these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0751 -        variables and carbohydrate and sialic acid content of isolated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0752 -        LDL.  There were significant inverse correlations ( r ) of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0753 -        carbohydrate measurements with levels of plasma triglyceride: -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0754 -        0.71 for glycolipid carbohydrate, - 0.57 for apoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0755 -        carbohydrate, and - 0.58 for total sialic acid (all P<O.OOl).
PD0756 -        Stepwise multiple logistic regression analysis showed that LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0757 -        particle diameter was a significant predictor of LDL total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0758 -        carbohydrate, apoprotein carbohydrate, and glycolipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0759 -        carbohydrate content.  Plasma triglyceride level contributed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0760 -        independently but less strongly to LDL total carbohydrate and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0761 -        glycolipid carbohydrate content, as well as to total sialic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0762 -        acid content.  Inclusion of HDL cholesterol, LDL cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0763 -        body mass index and age in the regression models did not change                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0764 -        these results.  Fig. 4 shows the relationships of plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0765 -        triglyceride concentration to LDL content of total carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0766 -        (Fig. 4A), apoprotein carbohydrate (Fig. 4B), and glycolipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0767 -        carbohydrate (Fig. 4C).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0769 -         ..
PD0770 -        HDL cholesterol concentration was positively correlated with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0771 -        glycolipid carbohydrate (7 = 0.39) and with glycoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0772 -        carbohydrate ( r = 0.49, P<O.Ol and P< 0.001, respectively) and
PD0773 -        less strongly with sialic acid ( r = 0.31, P<O.O5).  LDL
PD0774 -        cholesterol level showed a weak inverse correlation with LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0775 -        sialic acid content ( r = - 0.32, P<0.05), but not
PD0776 -        significantly with other carbohydrate parameters.  Body mass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0777 -        index was inversely correlated with LDL apoprotein carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0778 -        (r = - 0.39, P<O.Ol), and age was weakly correlated with
PD0779 -        glycolipid carbohydrate ( r = - 0.28, P<0.05).
PD0781 -         ..
PD0782 -        Table 3 presents apoprotein and glycolipid carbohydrate content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0783 -        of 11 LDL density subfractions isolated from six subjects each                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0784 -        with LDL patterns A and B.  Also shown are the buoyant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0785 -        densities and protein content of each fraction, as well as mean                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0786 -        particle diameters determined by gradient gel electrophoresis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0787 -        The distribution of protein mass across the density fractions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0788 -        differed as expected between the two groups of subjects, with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0789 -        relative increased mass of more buoyant and larger LDL in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0790 -        fractions 3 and 4 in subjects with pattern A (PCO.01 and P<
PD0791 -        0.05, respectively, by analysis of variance), and increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0792 -        mass of more dense and smaller LDL in fraction 7 in subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0793 -        with pattern B (P<0.05).  Both LDL particle diameter and LDL
PD0794 -        glycolipid carbohydrate declined significantly with increasing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0795 -        density of the LDL fractions, but analysis of variance showed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0796 -        no significant differences in these variables between pattern A                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0797 -        and pattern B subjects.  In contrast, analysis of variance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0798 -        revealed significant differences of apoLDL carbohydrate content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0799 -        both among the LDL subfractions (P< 0.0001) and between
PD0800 -        subjects with LDL subclass patterns A and B (P< O.OOOl), with
PD0801 -        no significant interaction between these parameters.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0802 -        results in Table 3 may also be compared with those shown in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0803 -        Table 2 and Fig. 2 for apoprotein and glycolipid carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0804 -        content of unfractionated LDL from subjects with LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0805 -        patterns A and B.  For subjects with pattern A, the peak                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0806 -        particle diameter (267 * 6 A, Table 1) and glycolipid and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0807 -        apoprotein carbohydrate content (Table 2) of unfractionated LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0808 -        are consistent with the size and carbohydrate content of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0809 -        particles isolated in density gradient fractions 3-6, which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0810 -        contain the bulk of LDL mass in pattern A subjects (Table 3).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0811 -        On the other hand, for subjects with pattern B, peak LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0812 -        diameter (250 * 6, Table 1) and LDL protein and lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0813 -        carbohydrate content (Table 2) of unfractionated LDL are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0814 -        comparable to the values for LDL particles in density fractions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0815 -        7-9 (Table 3).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0817 -         ..
PD0818 -        Discussion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0820 -         ..
PD0821 -        Previous studies using density gradient ultracentrifugation and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0822 -        nondenaturing gradient gel electrophoresis (13- 16) have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0823 -        established the existence of multiple distinct subclasses of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0824 -        plasma LDL.  Differences in lipid content (15, 46-48),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0825 -        apolipoprotein content (49, 50), and apoB immunoreactivity (32)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0826 -        have been reported across the LDL particle spectrum.  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0827 -        present study provides evidence that LDL carbohydrate content                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0828 -        also differs as a function of LDL diameter, since variation in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0829 -        total LDL carbohydrate content among individuals is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PD0830 -        proportional to LDL particle size as determined by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0831 -        nondenaturing gradient gel electrophoresis.  Approximately                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0832 -        one-half of the total carbohydrate is present as glycolipids,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0833 -        and the variation in glycolipid carbohydrate appears to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0834 -        directly proportional to the total lipid content of LDL.  Thus,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0835 -        it is possible that LDL glycolipid content may depend on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0836 -        metabolic events, such as lipolytic and transfer activities,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0837 -        that affect other LDL lipids.  Consistent with this is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0838 -        observation that plasma triglyceride level, which is related to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0839 -        relative LDL lipid content (49), was significantly associated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0840 -        with LDL glycolipid content.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0842 -         ..
PD0843 -        On the other hand, carbohydrate content of apoB also varies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0844 -        over a wide range (approximately 30-100 mg/g apoLDL), and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0845 -        relationship of apoLDL (apoB-100) carbohydrate to peak LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0846 -        particle diameter in both unfractionated LDL and LDL density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0847 -        subfractions suggests that the previously reported differences                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0848 -        in apoB carbohydrate in the range of 40-100 mg/g apoLDL (20-28)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0849 -        may be related in part to factors responsible for predominance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0850 -        of LDL subclasses of varying size.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0852 -         ..
PD0853 -        The relationship of apoB carbohydrate content to LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0854 -        size contributes to differences in apoB carbohydrate between                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0855 -        individuals with a predominant peak of larger LDL subclasses                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0856 -        (pattern A) and a major peak of smaller LDL (pattern B).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0857 -        Previous studies have shown that these two subclass patterns                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0858 -        appear to be under the influence of a dominant gene with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0859 -        population frequency of approximately 0.25 and full penetrance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0860 -        in men above age 20 and in women after menopause (17, 18).  The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0861 -        present findings suggest that differences in glycosylation of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0862 -        apoB, and possibly in glycosylation of LDL lipids, may be an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0863 -        important feature distinguishing the LDL of individuals with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0864 -        these two lipoprotein subclass phenotypes, and conceivably                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0865 -        could relate to the genetic determinant of these phenotypes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0867 -         ..
PD0868 -        Reduced carbohydrate content of LDL apoB in subjects with LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0869 -        subclass pattern B is not due simply to the predominance of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0870 -        smaller, denser, carbohydrate-depleted LDL subspecies.  LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0871 -        particles isolated across the entire size and density range                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0872 -        from pattern B subjects showed reduced apoB carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0873 -        content (but no differences in glycolipid carbohydrate content)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0874 -        in comparison with particles of comparable size and density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0875 -        from pattern A subjects.  Thus, in subjects with LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0876 -        pattern B, reductions in LDL apoB and glycolipid carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0877 -        content are associated both with reduced concentrations of more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0878 -        buoyant, carbohydrate-enriched LDL subspecies, and with reduced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0879 -        glycosylation of apoB in all LDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0881 -         ..
PD0882 -        Differences in apoB carbohydrate content between LDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0883 -        of differing size and density and between the two LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0884 -        patterns could originate with intrahepatic glycosylation of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0885 -        precursors, or could result from intravascular processing of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0886 -        lipoprotein particles.  Intravascular modification of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0887 -        glycoprotein or glycolipid could involve differential action of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0888 -        plasma glycosidases.  Plasma is known to contain a number of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0889 -        lysosomally derived glycosidases (51-58) including alpha and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0890 -        beta mannosidases and a neuraminidase activity.  In subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0891 -        with LDL subclass pattern B, there could be high activity of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0892 -        one or more of these enzymes, or possibly greater exposure to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0893 -        enzyme activity due to prolonged LDL plasma residence time.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0894 -        However, with the exception of neuraminidase (pH optimum of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0895 -        5.5), these acid glycosidases have pH optima below pH 5.0 and,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0896 -        based on their pH activity curves (54, 56-58), should not be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0897 -        active at plasma pH of 7.4.  In addition, kinetic studies in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0898 -        humans with primary hypertriglyceridemia (59) have found that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0899 -        relatively dense LDL with reduced cholesterol content typical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0900 -        of the smaller LDL species which predominate in LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0901 -        pattern ?3 (15) had a higher turnover rate, and thus a shorter                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0902 -        plasma residence time than did less dense LDL.  To further test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0903 -        for a possible role of plasma residence time, we isolated LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0904 -        from a subject heterozygous for familial hypercholesterolemia,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0905 -        a condition resulting from defective or absent LDL receptors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0906 -        and associated with reduced LDL clearance rate (60).  If                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0907 -        prolonged plasma residence time were responsible for reduced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0908 -        LDL carbohydrate content, LDL carbohydrate would be expected                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0909 -        to be reduced in such subjects.  However, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0910 -        hypercholesterolemic subject was found to have a predominance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0911 -        of large LDL particles and the high levels of carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0912 -        characteristic of pattern A LDL.  Although this observation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0913 -        will require confirmation in larger numbers of subjects, it is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0914 -        consistent with the findings described above which suggest that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0915 -        plasma glycoside activities are not responsible for observed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0916 -        differences in LDL carbohydrate content between pattern A and B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0917 -        LDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PD0919 -         ..
PD0920 -        There are several possible mechanisms by which carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0921 -        content of LDL precursors could be affected prior to secretion.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0922 -        Conceivably, the glycolipid and glycoprotein differences                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0923 -        between pattern A and B LDL could be due to a variation in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0924 -        apoB gene.  Restriction fragment length polymorphisms (RFLPs)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0925 -        in the apoB gene have been associated with altered                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0926 -        triglyceride, cholesterol, and apoB levels (61-65) and several                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0927 -        of these RFLPs have also been found to be associated with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0928 -        increased risk of coronary heart disease (65, 66).  Examination                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0929 -        of the nucleic acid sequence of apoB (37) shows that there are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0930 -        19 potential sites for N-glycosidic linkage (67) and at least                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0931 -        16 of these sites are reported to be glycosylated (68).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0932 -        Genetic differences in apoB structure might affect the number                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0933 -        of sites available for glycosylation or the transport of apoB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0934 -        through the Golgi apparatus with resulting differences in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0935 -        degree of glycosylation of both protein and lipids.  Recently                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0936 -        we have used analysis of the 3' hypervariable region of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0937 -        apoB gene (69) in six families to exclude linkage between the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0938 -        apoB gene and LDL subclass patterns (70).  Thus variation in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0939 -        the apoB gene does not appear to be the basis for differences                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0940 -        in LDL between subjects with LDL subclass patterns A and B.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0942 -         ..
PD0943 -        There are several steps in the post-translation processing of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0944 -        the apoB where differences in carbohydrate could be introduced.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0945 -        Although glycosylation begins in the rough ER during protein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0946 -        synthesis, the majority of carbohydrate processing occurs after                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0947 -        transfer to the Golgi apparatus where further processing of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0948 -        oligosaccharide chains continues as the nascent glycoprotein is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0949 -        transported from the cis Golgi through the medial and tram                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0950 -        Golgi.  Since subclass pattern B LDL have less neutral                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0951 -        carbohydrate than pattern A LDL, there may be a difference in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0952 -        transport to the tram Golgi or in oligosaccharide processing of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0953 -        complex chains in the tram Golgi.  As a result there may be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0954 -        fewer andfor less complete carbohydrate chains present in LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0955 -        from subjects with the LDL subclass pattern B phenotype.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0956 -        Possibly such differences in Golgi processing could be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0957 -        associated with other lipid abnormalities found in subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0958 -        with LDL subclass pattern B (17, 19).  Investigation of these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0959 -        possibilities will require isolation and sequencing of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PD0960 -        carbohydrate chains from both the pattern A and pattern B LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0961 -        subclasses, and further information regarding mechanisms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0962 -        involved in hepatic apoB glycosylation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0964 -         ..
PD0965 -        Another mechanism that could contribute to the differences in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0966 -        LDL carbohydrate between subjects with the two LDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0967 -        patterns is differential plasma clearance of carbohydrate-rich                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0968 -        LDL.  In this regard, it is interesting to note that clearance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0969 -        of many plasma glycoproteins involves a system of receptors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0970 -        that recognize desialylated (Le., mannose, N-acetylglucosamine,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0971 -        or L-fucose terminated) glycoproteins (71-74).  However, it is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0972 -        unlikely that such a system accounts for the differences we                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD0973 -        find since it has been reported that there are no differences                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0974 -        in catabolism of native and desialylated LDL in the pig (25) or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0975 -        binding to skin fibroblasts (75).  Further, treatment of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0976 -        with a mixture of glycosidases, which removed at least 80 7% of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0977 -        the carbohydrate on apoB, did not affect LDL binding and uptake                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0978 -        by human fibroblasts (26).  However, at present we cannot                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0979 -        exclude the possiblity that there is selective removal of LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0980 -        or LDL precursors based on differences in carbohydrates other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0981 -        than sialic acid, such as the absolute number or relative                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0982 -        content of high mannose and complex chains.  Either possibility                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0983 -        could result in differential clearance rates such as those                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0984 -        reported for rat liver glycoproteins (76); those with high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD0985 -        mannose chains were cleared much more rapidly than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PD0986 -        unglycosylated glycoproteins which, in turn, were cleared                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD0987 -        faster than glycoproteins with the complex type carbohydrate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0988 -        chains.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD0990 -         ..
PD0991 -        Differences in clearance or catabolism of LDL with differing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD0992 -        carbohydrate content could not, however, account for the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD0993 -        presence of differing amounts of apoB glycosylation among LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0994 -        particles in individual subjects.  Given the evidence reviewed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD0995 -        above that these differences are likely to arise from variation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0996 -        in intrahepatic processing of LDL precursors prior to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PD0997 -        secretion, the present observation suggests that some or all of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD0998 -        the multiple discrete subclasses of LDL described in previous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD0999 -        reports arise in parallel from different hepatic precursors,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1000 -        rather than sequentially from intravascular metabolism of a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1001 -        common precursor.  Such a conclusion is compatible with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD1002 -        previous evidence for the presence of multiple discrete VLDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1003 -        and IDL subclasses in human plasma (77), which in turn give                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1004 -        rise to different LDL products with in vitro lipolysis (78) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1005 -        intravascular metabolism in rats (79).  Studies are currently                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD1006 -        in progress to evaluate the possiblity that differential                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD1007 -        glycosylation of apoB among these precursors corresponds to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1008 -        differences in apoB glycosylation among their LDL products.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1010 -         ..
PD1011 -        An important question raised by this study is what role, if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1012 -        any, differences in LDL carbohydrate content may play in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1013 -        increased risk of heart disease present in individuals with LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1014 -        subclass pattern B (19) and a predominance of small, dense LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1015 -        (26, 50).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD1017 -         ..
PD1018 -        Direct interaction of LDL with components of artery walls is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1019 -        thought to play an important role in the development of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD1020 -        atherosclerosis.  Immunochemical methods have shown that apoB                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD1021 -        is present in atherosclerotic lesions (80) and LDL particles,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD1022 -        in the form of insoluble proteoglycan-lipoprotein complexes,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1023 -        have also been found to be present preferentially in these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PD1024 -        lesions (80-82).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PD1026 -         ..
PD1027 -        A negatively charged lipoprotein-complexing proteoglycan (LCP)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1028 -        has been isolated from human artery wall and was found to form                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1029 -        soluble and insoluble complexes with LDL (83).  Initially, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD1030 -        was found that LDL from different individuals formed different                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1031 -        amounts of insoluble complexes with LCP, with the largest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD1032 -        amount of insoluble complex formed from LDL with higher                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD1033 -        affinity for LCP (84, 85).  This led to the hypothesis that LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1034 -        with the higher affinity for LCP could be preferentially                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD1035 -        involved in the development of atherosclerosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1037 -         ..
PD1038 -        Later work found that the LDL population with greater affinity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1039 -        for LCP, and the greater tendency to form insoluble LDL-LCP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1040 -        complexes, possessed significantly less sialic acid than the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1041 -        LDL subclass with relatively low affinity for LCP (84).  In                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1042 -        addition, desialation of LDL with neuraminidase was found to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1043 -        increase affinity of LDL for LCP (84) and, in vivo, to increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1044 -        uptake of LDL by the arterial intima-media (85).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PD1046 -         ..
PD1047 -        Based on these reports, LDL subclass pattern B LDL, with its                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1048 -        lower sialic acid content, would be predicted to show stronger                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1049 -        binding than LDL from subclass pattern A to at least one human                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PD1050 -        arterial proteoglycan with potential for increasing deposits of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1051 -        an insoluble LDL-LCP complex in the arterial wall.  Since we                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PD1052 -        have shown here that the reduction in LDL sialic content in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PD1053 -        pattern B subjects is related to differences in LDL glycolipids                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PD1054 -        and not to apoB glycosylation, it may be that altered LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PD1055 -        glycolipid composition could contribute to the increased risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PD1056 -        of coronary heart disease found in individuals with LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PD1057 -        subclass pattern B.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PD1058 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD1059 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD1060 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD1061 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PD11 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PE03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PE0401 -  ..
PE0402 - HDL Particle Count Increased with Exercise Lowers CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0403 - 
PE0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0405 -        Medscape                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0407 -   16.  Higher HDL-Particle Concentrations Associated With Reduced CHD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0408 -        Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0410 -              http://www.medscape.com/viewarticle/767250                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0412 -         ..
PE0413 -        Michael O'Riordan                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PE0415 -         ..
PE0416 -        July 11, 2012                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0417 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0418 -        1.  July 11, 2012 (Pittsburgh, Pennsylvania) - A new analysis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0419 -            of the Multi-Ethnic Study of Atherosclerosis (MESA) sheds                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0420 -            some light on the complicated association between HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0421 -            cholesterol and coronary heart disease risk, with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PE0422 -            researchers showing that the concentration of HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PE0423 -            particles was independently associated with carotid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0424 -            intima-media thickness (cIMT) and coronary heart disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0425 -            [1].                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0427 -             ..
PE0428 -        2.  HDL cholesterol was also inversely associated with cIMT and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0429 -            coronary heart disease events, but the association was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0430 -            attenuated when adjusted for atherogenic lipoproteins and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0431 -            HDL particles.  In contrast, the association between                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0432 -            HDL-particle concentration and cIMT and coronary heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0433 -            disease risk was unaffected when adjusted for atherogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0434 -            lipoproteins, HDL cholesterol, and mean HDL-particle size.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0436 -             ..
PE0437 -        3.  "Our study, essentially, wasn't measuring the cargo the HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0438 -            cholesterol was carrying," lead investigator Dr Rachel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0439 -            Mackey (University of Pittsburgh, PA) told heartwire . "As                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0440 -            we're seeing more and more puzzling results by using HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0441 -            cholesterol to represent the particles, it makes a lot of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0442 -            sense that these other atherogenic functions of HDL would                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0443 -            be better represented by how many particles there are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0444 -            rather than by the cholesterol they carry.  I'm not sure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0445 -            there is even a biological reason to think that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0446 -            cholesterol they carry would be a good measure--it was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0447 -            simply what was able to be checked."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0449 -             ..
PE0450 -        4.  The results suggest that quantification of HDL cholesterol,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0451 -            which is the cholesterol carried by HDL particles, might                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0452 -            not "fully capture the HDL-related risk," according to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0453 -            researchers.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PE0455 -             ..
PE0456 -        5.  In an editorial accompanying the study [2], Drs Emil                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0457 -            deGoma and Daniel Rader (University of Pennsylvania,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0458 -            Philadelphia) state that in the setting of HDL-directed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0459 -            therapies, "a consistent inverse relationship between HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0460 -            cholesterol and cardiovascular risk can no longer be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0461 -            assumed." The independent association of HDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0462 -            with coronary heart disease suggests that it might serve                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0463 -            as a better marker of risk than HDL cholesterol and might                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0464 -            prove more useful to assess HDL-directed pharmacotherapies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0465 -            and that increasing HDL-particle concentrations might                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0466 -            prove to be more appropriate than increasing HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0467 -            cholesterol for reducing the risk of cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0468 -            events.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0470 -             ..
PE0471 -        6.  The results of the study and the editorial are published                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0472 -            online July 11, 2012 in the Journal of the American                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0473 -            College of Cardiology.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0475 -             ..
PE0476 -        7.  HDL Particles Measured With NMR Spectroscopy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PE0478 -             ..
PE0479 -            To heartwire , Mackey noted that the particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PE0480 -            concentrations of LDL, in certain populations, are a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0481 -            better reflection of atherogenic lipoprotein particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0482 -            than the cholesterol carried by the LDL molecule.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PE0483 -            Similarly, the HDL particles are known to have a variety                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0484 -            of functions, including carrying the cholesterol, and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0485 -            group hypothesized that if they measured the lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0486 -            particles using nuclear magnetic resonance (NMR)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0487 -            spectroscopy it might provide a better picture of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0488 -            functionality of HDL. Mackey noted that HDL is a complex                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0489 -            molecule and that in addition to reverse cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0490 -            transport, the molecule also appears to carry antioxidant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0491 -            proteins and have anticoagulant and anti-inflammatory                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0492 -            effects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0494 -             ..
PE0495 -        8.  Using data from the MESA study, a study of 5598 men and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0496 -            women aged 45 to 84 years old without baseline coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0497 -            heart disease, the researchers tested the associations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0498 -            between HDL cholesterol and NMR spectroscopy-measured                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0499 -            HDL-particle numbers with cIMT and incident MI, coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0500 -            heart disease death, and angina. After a mean six-year                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0501 -            follow-up, 227 coronary heart disease events were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PE0502 -            documented.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0504 -                ..
PE0505 -               [On 140201 1159 obtained blood draw for Lipid NMR test                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PE0506 -               LDL-P at Labcor on Health Testing Centers order # 27716.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0507 -               ref SDS 53 KQ4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0509 -             ..
PE0510 -        9.  Overall, HDL-particle concentrations were positively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0511 -            correlated with HDL-cholesterol levels and both had an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0512 -            inverse correlation with LDL cholesterol, LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0513 -            concentrations, and with other metabolic risk factors.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0514 -            Adjusted for confounding variables, mean cIMT was lower                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0515 -            among patients with higher concentrations of HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0516 -            cholesterol and HDL particles. One-standard-deviation (SD)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0517 -            increase in the concentrations of HDL cholesterol (15                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0518 -            mg/dL) or HDL particles (6.64 µmol/L) was associated with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0519 -            a 0.026-mm and 0.030-mm reduction in cIMT, respectively.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0520 -            Each SD-increase in HDL cholesterol and HDL-particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0521 -            concentrations was also associated with a significant 26%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0522 -            and 30% lower risk of coronary heart disease events.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0524 -             ..
PE0525 -       10.  Risk of Incident Coronary Heart Disease With 1-SD Increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0526 -            in HDL Cholesterol and HDL-Particle Concentration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PE0528 -             ..
PE0529 -            [...table omitted...]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0531 -             ..
PE0532 -       11.  The inverse relationship between HDL cholesterol and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0533 -            coronary heart disease events and carotid atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0534 -            was attenuated when separately adjusted for LDL- and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0535 -            HDL-particle concentrations and disappeared entirely when                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0536 -            adjusted for both.  On the other hand, HDL-particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0537 -            concentrations remained associated with cIMT and coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0538 -            heart disease events after adjustment for LDL particles,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0539 -            HDL cholesterol, or both.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0541 -             ..
PE0542 -       12.  "When we adjust for the atherogenic particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PE0543 -            [concentration] that HDL cholesterol is associated with, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PE0544 -            explains a large amount of the inverse association between                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0545 -            HDL cholesterol and outcomes," said Mackey. "It explains                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0546 -            pretty much none of the relationship between HDL particles                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0547 -            and outcomes."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PE0549 -             ..
PE0550 -       13.  Future Studies Need to Account for HDL-Particle Changes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0552 -             ..
PE0553 -            The assay used to measure HDL and LDL particles--which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0554 -            detects distinct lipoprotein subclass by subjecting them to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0555 -            electromagnetic pulses--is already commercially available,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0556 -            the authors note. The ability to measure HDL-particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0557 -            concentrations does not eliminate the importance of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0558 -            traditional lifestyle modifications known to influence HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0559 -            cholesterol, however.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0560 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0562 -  ..
PE0563 - CVD Risk Requires Measuring HDL Particle Count with NMR Testing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0564 - Exercise HDL Particle Count Decrease Lowers CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0565 - HDL Exercise Increase Particle Count Lowers CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0566 - Medication Raises HDL Cholosterol But Not HDL Particle Count                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PE0567 - 
PE0568 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0569 -       14.  "So, on the one hand, for the average person, raising HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0570 -            cholesterol with physical activity, smoking cessation, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0571 -            watching your diet is a good idea, as it should also raise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0572 -            the HDL particles," Mackey told heartwire . "Where this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0573 -            becomes really important is with trials focusing on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0574 -            pharmacologically raising HDL cholesterol. We've seen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0575 -            several where it's been raised, but HDL particles have not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0576 -            been raised, and so we're not seeing the expected benefit.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0577 -            Our study would suggest that as people are moving forward                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0578 -            in the HDL therapeutic area, they should pay attention to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0579 -            what's going with the particles."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PE0581 -             ..
PE0582 -       15.  In their editorial, deGoma and Rader note that few studies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0583 -            have examined the effect of existing and emerging drugs on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0584 -            HDL-particle concentrations.  A post hoc analysis of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0585 -            Veterans Affairs High-Density Lipoprotein Intervention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0586 -            Trial (VA-HIT) with gemfibrozil did show on-treatment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0587 -            HDL-particle levels were strongly associated with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0588 -            reduction in coronary heart disease events while HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0589 -            cholesterol was not.  A similar analysis of the AIM-HIGH                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0590 -            study, where extended-release niacin failed to show a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PE0591 -            benefit, would be of interest, as would the effect of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PE0592 -            new cholesteryl ester-transfer protein (CETP) inhibitors on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0593 -            HDL-particle concentrations.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PE0595 -             ..
PE0596 -       16.  The editorialists highlight several important questions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0597 -            that need to be addressed in future studies.  What, they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0598 -            ask, is the biological explanation for the more robust                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0599 -            association between HDL particles and cardiovascular risk?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0600 -            "Identifying which aspects of HDL functionality are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PE0601 -            uniquely captured by [HDL particles] and not HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PE0602 -            cholesterol represents an important next step," they write.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0603 -            In addition, they wonder in which patients HDL-particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0604 -            measurements might be reasonable to help refine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PE0605 -            cardiovascular risk.  Calibration, discrimination, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0606 -            reclassification analyses will be needed to help clarify                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0607 -            the role of HDL-particle measurements above and beyond                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0608 -            traditional cardiovascular risk factors, they write.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0610 -             ..
PE0611 -       17.  This research was supported by contracts from the National                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0612 -            Heart, Lung, and Blood Institute.  Mackey was supported by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PE0613 -            an unrestricted research grant from LipoScience to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PE0614 -            University of Pittsburgh.  Disclosures for the coauthors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PE0615 -            are listed in the paper. deGoma has reported that he has no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PE0616 -            relationships relevant to the contents of this paper to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0617 -            disclose.  Rader has relationships with LipoScience and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PE0618 -            Vascular Strategies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0619 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0620 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0621 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE0622 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PE07 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PF03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PF0401 -  ..
PF0402 - HDL Large Particle Size Lowers CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PF0403 - 
PF0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0405 -        Pubmed.gov                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PF0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0407 -        Atherosclerosis. 2009 Sep;206(1):276-81. doi:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PF0408 -        10.1016/j.atherosclerosis.2009.01.044. Epub 2009 Feb 12.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0410 -         ..
PF0411 -   17.  HDL particle size and the risk of coronary heart disease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PF0412 -        apparently healthy men and women: the EPIC-Norfolk prospective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PF0413 -        population study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PF0414 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0415 -              http://www.ncbi.nlm.nih.gov/pubmed/19268944                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PF0417 -         ..
PF0418 -        Arsenault BJ, Lemieux I, Després JP, Gagnon P, Wareham NJ,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PF0419 -        Stroes ES, Kastelein JJ, Khaw KT, Boekholdt SM.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0421 -         ..
PF0422 -        Author information                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PF0424 -         ..
PF0425 -        Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0426 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0427 -        1.  OBJECTIVE:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PF0428 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0429 -            To evaluate the association between HDL particle size                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PF0430 -            measured by gradient gel electrophoresis and risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0431 -            incident coronary heart disease (CHD) in apparently healthy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0432 -            men and women.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PF0434 -             ..
PF0435 -        2.  METHODS:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PF0436 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0437 -            We performed a prospective case-control study nested in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0438 -            EPIC-Norfolk cohort.  Cases were apparently healthy men and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0439 -            women aged 45-79 years who developed fatal or nonfatal CHD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PF0440 -            (n=1035). They were matched to 1920 controls who remained                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PF0441 -            free of CHD over the follow-up period of 6 years.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PF0443 -             ..
PF0444 -        3.  RESULTS:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PF0445 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0446 -            Participants with the smallest HDL particles had the most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PF0447 -            unfavourable cardiometabolic risk profile whereas those                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PF0448 -            with the largest HDL particles had the most favourable risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0449 -            profile.  Plasma HDL cholesterol levels were found to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PF0450 -            the best correlate of HDL particle size (r=0.58 and r=0.62,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0451 -            respectively, for men and women, p<0.001).  Men in the
PF0452 -            highest quartile of HDL particle size had an unadjusted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PF0453 -            odds ratio (OR) for future CHD of 0.75 (95% CI, 0.57-0.97)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PF0454 -            compared to those in the bottom quartile.  For women, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PF0455 -            equivalent OR was 0.50 (0.35-0.71).  After additional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PF0456 -            adjustment for diabetes, body mass index, systolic blood                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PF0457 -            pressure, LDL and HDL cholesterol levels, the ORs were 1.43                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0458 -            (1.01-2.03) in men and 0.84 (0.52-1.35) in women.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PF0460 -             ..
PF0461 -        4.  CONCLUSIONS:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PF0462 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0463 -            A decreased HDL particle size is associated with an adverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PF0464 -            cardiometabolic risk profile.  Small HDL particle size was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PF0465 -            also associated with an increased CHD risk, but this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0466 -            association was largely explained by traditional risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PF0467 -            factors.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PF0468 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0469 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0470 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0471 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0472 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF0473 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PF05 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0401 -  ..
PG0402 - HDL Very Large Particle Size Increases CVD Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0403 - 
PG0404 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0405 -        Medscape                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0407 -   18.  HDL Cholesterol, HDL Particle Size and Apolipoprotein A-I:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0408 -        Significance for Cardiovascular Risk ? The IDEAL &                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0409 -        EPIC-Norfolk Studies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0411 -         ..
PG0412 -        Wim A van der Steeg, MD, Christopher P Cannon, MD, FACC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0413 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0414 -              http://www.medscape.com/viewarticle/571347_1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0415 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0416 -        1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0417 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0418 -            The European Prospective Investigation into Cancer and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0419 -            Nutrition (EPIC)-Norfolk study is part of the largest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0420 -            prospective evaluation of diet and health ever undertaken.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0421 -            The entire EPIC study involves more than half a million                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0422 -            people in 10 countries. The EPIC-Norfolk portion of this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0423 -            effort is a prospective population study of 25,663 men and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0424 -            women aged 45-79 years residing in Norfolk, United                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0425 -            Kingdom, who completed a baseline questionnaire survey and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0426 -            attended a clinic visit.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0428 -             ..
PG0429 -        2.  EPIC should produce much more specific information about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0430 -            the effect of diet and lifestyle on long-term health than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0431 -            previous studies. Moreover, the database includes the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0432 -            potential for many other studies given the detailed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0433 -            information collected on height, weight, waist and hip                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0434 -            measurements, and blood samples stored in liquid nitrogen.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0435 -            To date, some 100 papers have been published using the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0436 -            EPIC-Norfolk cohort.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0438 -             ..
PG0439 -        3.  For example, the data have been used in a series of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0440 -            studies to determine the value of lipid subfractions in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0441 -            clinical risk assessment. In early 2007, Harchaoui and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0442 -            colleagues reported in JACC the results of a nested                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0443 -            case-control study of EPIC-Norfolk participants.[1]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0444 -            Several lines of evidence had suggested that small, dense                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0445 -            low-density lipoprotein (LDL) particles are more highly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0446 -            atherogenic than larger-sized particles, yet the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0447 -            traditional lipid profile cannot discern whether elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0448 -            levels of LDL reflect small or large particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG0449 -            EPIC-Norfolk participants were used to find individuals                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0450 -            who developed coronary artery disease (CAD) during 6-year                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0451 -            follow-up (cases, n = 1,003) and for control subjects (n =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0452 -            1,885), who were matched for age, gender, and enrollment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0453 -            time.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0455 -             ..
PG0456 -        4.  The investigators compared the ability of LDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0457 -            number (LDL-P), LDL particle size (LDL-S), and several                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0458 -            established cardiovascular risk factors to predict the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0459 -            first cardiac event in these subjects. LDL-S correlated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0460 -            inversely with risk for coronary artery disease, and LDL-P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0461 -            was more predictive than LDL alone (Figure 1); however,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0462 -            after adjusting for high-density lipoprotein cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0463 -            (HDL-C) and triglycerides, neither test was superior. The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0464 -            study confirmed that LDL-P and LDL-S add additional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0465 -            information to cardiovascular risk, but little additional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0466 -            information compared to non-HDL-C.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0468 -             ..
PG0469 -        5.  They concluded that their findings do not support routine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0470 -            use of LDL-P in CAD risk assessment strategies for primary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0471 -            prevention.  However, the added recognition that patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0472 -            with low HDL-C and/or high triglycerides often have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0473 -            elevated numbers of LDL particles without having elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0474 -            LDL-C may enable their LDL-related CAD risk to be managed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0475 -            more effectively.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PG0477 -             ..
PG0478 -        6.  Apolipoproteins for Risk Assessment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0479 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0480 -            So, LDL-P may play a useful role in patient management by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0481 -            helping judge the adequacy of LDL-lowering therapy,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0482 -            particularly among those with elevated triglycerides and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0483 -            reduced HDL-C. Such a role also has been proposed for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0484 -            apolipoprotein B (apo B). Indeed, both non-HDL-C and apo B                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0485 -            have been proposed as secondary treatment targets after                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0486 -            LDL-C goals have been achieved.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG0488 -             ..
PG0489 -        7.  A few months after the 2007 JACC study was published, many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0490 -            of the same investigators ? this time led by Wim A. van                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0491 -            der Steeg, MD ? published a paper looking at the role of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0492 -            the apo B-apolipoprotein A-I (apo B-apo A-I) ratio in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0493 -            cardiovascular risk assessment.[2] Prior to this analysis,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0494 -            recent studies had shown that the apo B apoA-I ratio was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0495 -            strongly associated with future CAD. This association and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0496 -            the ability to measure apolipoprotein in nonfasting blood                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0497 -            samples had led to recommendations that the apo B-apo A-I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0498 -            ratio be used in routine clinical care,[3] despite the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0499 -            fact that it was not known whether this ratio is better                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0500 -            than traditional lipid values for risk assessment and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0501 -            prediction and whether it adds predictive value to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0502 -            Framingham risk score.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0504 -             ..
PG0505 -        8.  The EPIC-Norfolk investigation was used to select cases,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0506 -            who were apparently healthy men and women (45 to 79 years                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0507 -            of age) who developed fatal or nonfatal CAD (n = 869), and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0508 -            controls (n = 1,511), who were persons without CAD and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0509 -            again were matched for age, sex, and enrollment period.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0510 -            (Note: Few people with diabetes and no one using                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0511 -            lipid-lowering medication participated in the study.) The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0512 -            apo B-apo A-I ratio was associated with future CAD events,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0513 -            independent of traditional lipid values (adjusted odds                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0514 -            ratio, 1.85 [95% CI, 1.15 to 2.98]), including the total                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0515 -            cholesterol-HDL-C ratio, and independent of the Framingham                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0516 -            risk score (adjusted odds ratio, 1.77 [CI, 1.31 to 2.39]).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0518 -             ..
PG0519 -        9.  However, it did no better than lipid values at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PG0520 -            discriminating between CAD cases and controls and added                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0521 -            little to the predictive value of the Framingham risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0522 -            score. Moreover, it incorrectly classified 41.1% of cases                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0523 -            and 50.4% of controls.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0525 -             ..
PG0526 -       10.  In the February 12th, 2008 issue of JACC, van der Steeg et                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0527 -            al. assessed the relationships of plasma HDL-C and HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0528 -            particle size with CAD risk, with a particular emphasis on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0529 -            very high values of these parameters.[4] They also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0530 -            evaluated the relationship for apoA-I.  This post-hoc                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0531 -            analysis used data from the EPIC-Norfolk study as well as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0532 -            the large Incremental Decrease in End Points through                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0533 -            Aggressive Lipid Lowering (IDEAL) trial (n = 8,888), which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0534 -            compared the efficacy of high-dose to usual-dose statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0535 -            treatment for the secondary prevention of cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0536 -            events (Figure 2).[5] The IDEAL dataset contained data on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0537 -            HDL-C and apoA-I, whereas the EPIC-Norfolk dataset (858                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0538 -            cases, 1,491 control patients) additionally had values of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0539 -            HDL particle size as measured by nuclear magnetic resonance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0540 -            (NMR) spectroscopy.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0542 -             ..
PG0543 -       11.  When researchers adjusted for levels of apo B and apo A-I,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0544 -            very high values of HDL-C (>70 mg/dl) and HDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0545 -            size (>9.5 nm) were associated with increased risk of CAD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PG0546 -            (Figure 3 and Figure 4). These results suggest that large                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0547 -            HDL particles increase cardiac risk, possibly by serving                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0548 -            as cholesterol donors rather than scavengers.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PG0550 -             ..
PG0551 -       12.  This summary, prepared for Cardiosource by Wim A van der                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0552 -            Steeg, MD, of the University of Amsterdam, Amsterdam,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0553 -            Netherlands, discusses this new study in JACC and how the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0554 -            observations may have important consequences for future CAD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0555 -            risk assessment and novel treatment strategies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG0557 -             ..
PG0558 -       13.  Summary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0560 -             ..
PG0561 -            High plasma levels of high-density lipoprotein cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0562 -            (HDL-C) are inversely related to the risk of coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0563 -            artery disease (CAD).[6,7] For apolipoprotein A-I (apo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0564 -            A-I), which is the main protein constituent of the HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0565 -            particle, identical results have been reported.[8] These                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0566 -            observations have led to the development of novel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PG0567 -            therapies that raise plasma levels of HDL-C or apoA-I in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0568 -            order to further decrease risk of CAD.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0570 -             ..
PG0571 -       14.  Recently, a couple of clinical studies were published,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0572 -            evaluating the effect of elevation of plasma HDL-C levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0573 -            via torcetrapib, which is an inhibitor of the cholesteryl                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0574 -            ester transfer protein.[9-12] In these studies,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG0575 -            considerable increases of plasma HDL-C and apoA-I were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0576 -            observed in patients receiving torcetrapib. Nevertheless,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0577 -            torcetrapib did not induce the expected regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0578 -            atherosclerosis. In fact, an increase of atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0579 -            was observed.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PG0581 -             ..
PG0582 -       15.  As extensively discussed in literature, this unexpected                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0583 -            outcome is hypothesized to relate to the rise of systolic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0584 -            blood pressure observed in patients receiving torcetrapib.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0585 -            However, a second possible explanation pertains to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0586 -            structural changes of the HDL particle induced by CETP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0587 -            inhibition. In fact, it has been hypothesised that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0588 -            very large HDL particles, which become predominant when                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0589 -            HDL-C levels rise upon CETP inhibition, may be less                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0590 -            effective in exerting antiatherogenic functions.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0592 -             ..
PG0593 -       16.  This would suggest that the previously reported inverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0594 -            relationships of HDL-C and apo A-I with CAD do not hold                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0595 -            true for very high levels of these parameters. Therefore,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0596 -            the present study was conducted to reassess the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG0597 -            relationship of HDL-C, HDL particle size and apo A-I with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0598 -            the occurrence of CAD, with a focus on the effect of very                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0599 -            high values of these parameters.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0601 -             ..
PG0602 -       17.  To accomplish this, we performed a post-hoc analysis of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0603 -            two prospective studies: the Incremental Decrease in End                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0604 -            Points through Aggressive Lipid Lowering (IDEAL) trial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0605 -            (n=8,888) comparing the efficacy of high-dose to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0606 -            usual-dose statin treatment for the secondary prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0607 -            of cardiovascular events,[4] and the European Prospective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0608 -            Investigation into Cancer and Nutrition (EPIC)-Norfolk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0609 -            case-control study, including apparently healthy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0610 -            individuals who did (cases, n=858) or did not (controls,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0611 -            n=1,491) develop CAD during follow-up.[4] In IDEAL, only                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0612 -            HDL-C and apo A-I were available; in EPIC-Norfolk, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0613 -            particle sizes determined by nuclear magnetic resonance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0614 -            (NMR) were also available.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0616 -             ..
PG0617 -       18.  The occurrence of a major adverse coronary event (MACE)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0618 -            was selected as the outcome variable for this analysis. In                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0619 -            the IDEAL study, this was the primary endpoint, defined as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0620 -            coronary death, non-fatal myocardial infarction, or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0621 -            resuscitation after cardiac arrest. In EPIC-Norfolk, MACE                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0622 -            included fatal or nonfatal CAD, defined as codes 410-414                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0623 -            according to the International Classification of Diseases,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0624 -            9th revision.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PG0626 -             ..
PG0627 -       19.  In the IDEAL dataset, the relationships of HDL-C and apo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0628 -            A-I with MACE were calculated by a Cox proportional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0629 -            hazards model, yielding values for relative risk (RR) for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0630 -            a one standard deviation (SD) increase of HDL-C or apo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0631 -            A-I. The basic regression model included covariates for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0632 -            age, sex, and smoking status (current, former, never)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0633 -            recorded at baseline. Body mass index (BMI) was not taken                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0634 -            into account because this parameter did not significantly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0635 -            contribute to the regression models. Data on alcohol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0636 -            consumption were not available in the IDEAL database.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0638 -             ..
PG0639 -       20.  In EPIC-Norfolk, the relationships of HDL-C, HDL particle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0640 -            size, and apo A-I with MACE were determined by conditional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0641 -            logistic regression analysis that took into account the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0642 -            matching for age, gender, and enrollment period, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0643 -            included the covariates smoking status (current, former,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0644 -            never), BMI, and alcohol consumption (number of units per                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0645 -            week) (basic model). MACE risk estimates were expressed as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0646 -            odds ratios (OR) for a one SD increase of HDL-C, HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0647 -            particle size, or apo A-I, with 95% confidence intervals.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0649 -             ..
PG0650 -       21.  When HDL-C and HDL particle size were evaluated, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0651 -            regression models were additionally adjusted for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0652 -            confounding by apo A-I. When apo A-I was evaluated,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0653 -            additional adjustment was performed for HDL-C or HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0654 -            particle size. Finally, all statistical models included apo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0655 -            B to account for differences in the proatherogenic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PG0656 -            lipoprotein fraction.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0658 -             ..
PG0659 -       22.  In the IDEAL study, we observed that plasma levels of HDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0660 -            were indeed inversely related to MACE following adjustment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0661 -            for the basic covariates as well as for apo A-I and apo B.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0662 -            However, at very high levels of HDL-C (?70 mg/dL), this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0663 -            inverse relationship disappeared. In fact, HDL-C turned out                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0664 -            to be a statistically significant risk factor at these high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0665 -            values.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0667 -             ..
PG0668 -       23.  Identical results were obtained for HDL particle size in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0669 -            EPIC-Norfolk. This parameter was inversely related to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0670 -            occurrence of MACE, but turned to a significant risk factor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0671 -            in the tail of its distribution upon adjustment for the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0672 -            basic covariates and apo A-I and apo B. In contrast, apo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0673 -            A-I remained negatively associated across the major part of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0674 -            its distribution in both studies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PG0676 -             ..
PG0677 -       24.  These data demonstrate that when apoA-I and apoB are kept                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0678 -            constant, HDL-C and HDL particle size may confer risk at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0679 -            very high values. This may suggest that the unexpected                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0680 -            outcome of the torcetrapib trials indeed results from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0681 -            factors related to the induced increase of HDL-C or the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0682 -            size of this lipoprotein. However, additional studies are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0683 -            required to further substantiate this hypothesis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PG0685 -             ..
PG0686 -       25.  There is no clear biological explanation how HDL can become                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0687 -            proatherogenic. This only permits speculation when it comes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0688 -            to biological mechanisms for our observations. First, some                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0689 -            of the exchange of cholesterol esters between HDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0690 -            peripheral cells is known to be bidirectional, in part                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0691 -            mediated by the scavenger receptor class B1.[13]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0693 -             ..
PG0694 -       26.  This observation gives rise to the hypothesis that very                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PG0695 -            large HDL, which are cholesterol enriched, may at some                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0696 -            point become a cholesterol donor instead of an acceptor.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0697 -            Second, although it has widely been acknowledged that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0698 -            anti-inflammatory capacity of HDL contributes to its                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0699 -            antiatherogenic potency, several studies have demonstrated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0700 -            that HDL can also turn into a proinflammatory particle.[14]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0701 -            Possibly, via these two latter mechanisms, a very high                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0702 -            plasma concentration of large HDL particles might in fact                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0703 -            induce a proatherogenic lipoprotein profile.  However,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0704 -            whether any of these two mechanisms has any physiological                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0705 -            relevance in humans needs certainly to be confirmed in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PG0706 -            further studies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PG0708 -             ..
PG0709 -       27.  Guidelines: Executive summary of the third report of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0710 -            National Cholesterol Education Program (NCEP) expert panel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0711 -            on detection, evaluation, and treatment of high blood                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PG0712 -            cholesterol in adults (Adult Treatment Panel III).  JAMA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PG0713 -            2001;285:2486-97.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PG0715 -             ..
PG0716 -       28.  Grundy SM, Cleeman JI, Merz CN; Coordinating Committee of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PG0717 -            the National Cholesterol Education Program. Implications of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PG0718 -            recent clinical trials for the National Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PG0719 -            Education Program Adult Treatment Panel III Guidelines.  J                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PG0720 -            Am Coll Cardiol 2004;44:720-32.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PG0721 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0722 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0723 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG0724 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PG08 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PH03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0401 -  ..
PH0402 - Regression Arterialsclerosis Occurs with Lower LDL and Higher HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0403 - Arterialsclerosis Regression Occurs with Lower LDL and Higher HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0404 - 
PH0405 - Patient suffered arterial plaque buildup that required CABG x4 on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0406 - 091022, ref SDS 5 PQWU, following report of chest pain while hiking                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0407 - hills a month earlier on 090908 1130. ref SDS 3 MY4N   Arterial plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0408 - buildup is evident in patient history of lipid panel showing low HDL <
PH0409 - 33 at least for period 2006 - 2009, when surgery was performed,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0410 - reported several months hence on 140203 1147. ref SDS 54 W25L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0412 -  ..
PH0413 - Subsequent to surgery in 2009, and beginning in 2011, HDL has steadily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0414 - increased to 61 in Labcorp blood test on 140201 1159. ref SDS 53 5C7M                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PH0415 - Concurrently, triglycerides have consistently dropped below 100, shown                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0416 - in VA lab 2 days later - TG 47 - on 140203 1147. ref SDS 54 5C7M                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0418 -  ..
PH0419 - While this condition seems to suggest progression of plaque buildup in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0420 - arteries has ended, there is a question if existing plaque can regress                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0421 - to clear prior buildup?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0423 -  ..
PH0424 - Research found...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0425 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0426 -   19.  Nature Clinical Practice                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0427 -        Cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0428 -        Medicine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0430 -         ..
PH0431 -        Rapid regression of atherosclerosis:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0432 -        insights from the clinical and experimental literature                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0433 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0434 -              http://www.nature.com/nrcardio/journal/v5/n2/full/ncpcardio1086.html                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0436 -         ..
PH0437 -        Nature Clinical Practice Cardiovascular Medicine (2008) 5,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0438 -        91-102                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0439 -        doi:10.1038/ncpcardio1086                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0440 -        Received 7 March 2007 | Accepted 17 October 2007                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0442 -         ..
PH0443 -        Kevin Jon Williams*, Jonathan E Feig and Edward A Fisher*                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0445 -         ..
PH0446 -        About authors...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0447 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0448 -              http://www.nature.com/nrcardio/journal/v5/n2/authors/ncpcardio1086.html                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PH0450 -         ..
PH0451 -        Email k_williams@mail.jci.tju.edu                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PH0452 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0453 -        1.  The idea that human atheromata can regress at all has met                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0454 -            considerable resistance over the decades.1, 2 Resistance to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0455 -            the idea of lesion regression is strengthened by the fact that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0456 -            advanced atheromata in humans and in animal models contain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0457 -            components that give an impression of permanence, such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0458 -            necrosis, calcification and fibrosis. In addition, numerous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0459 -            theories have been proposed to explain atherogenesis that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0460 -            include processes thought to be difficult, if not impossible,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PH0461 -            to reverse including oxidation,3 injury,4 and cellular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0462 -            transformations resembling carcinogenesis.5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0464 -             ..
PH0465 -        2.  In this Review we summarize the failure of many established                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0466 -            and experimental interventions to induce plaque regression,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0467 -            and examine other data indicating that sufficiently drastic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0468 -            changes in the plaque environment can stabilize and cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0469 -            regression of even advanced lesions.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0471 -  ..
PH0472 - CT & Intravasuclar Ultrasonography IVUS Quantify Arterial Plaque Change                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0473 - IVUS Intravasuclar Ultrasonography CT & Quantify Arterial Plaque Change                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0474 - Regression Atherosclerosis Measure Plauqe with CT and IVUS Technology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0475 - Atherosclerosis Regression Measure Plauqe with CT and IVUS Technology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0476 - 
PH0477 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0478 -        3.  REGRESSION DOCUMENTED BY DIRECT VESSEL-WALL IMAGING                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0479 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0480 -            Statins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0482 -             ..
PH0483 -            In order to track potentially more important changes in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0484 -            plaque composition, and to avoid the confounding effects of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0485 -            lesion remodeling on lumen size, arterial wall imaging is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0486 -            required.  Recent human trials have switched from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0487 -            quantitative angiography, which images only the vascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0488 -            lumen, to techniques that image plaque calcium (e.g.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0489 -            electron-beam CT) and plaque volume (e.g. intravascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0490 -            ultrasonography; IVUS).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0491 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0493 -  ..
PH0494 - Regression Arterialsclerosis Plaque 6.8% Rosuvastatin High Dose 18 Months                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PH0495 - Statin High Dose 18 Months Lower LDL-C < 60 and > 50% Reduce Plaque 6.8%
PH0496 - 
PH0497 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0498 -            A retrospective analysis found that aggressive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0499 -            LDL-cholesterol lowering with statins correlated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PH0500 -            significantly with reduction in coronary calcium-volume                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0501 -            score by electron-beam CT, indicating that coronary artery                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0502 -            calcifications can shrink.66  In the Reversal of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PH0503 -            Atherosclerosis with Aggressive Lipid Lowering (REVERSAL)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0504 -            study67 and A Study to Evaluate the Effect of Rosuvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0505 -            on Intravascular Ultrasound-Derived Coronary Atheroma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0506 -            Burden (ASTEROID),68 patients with acute coronary syndromes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0507 -            were treated for over a year with high-dose statins and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0508 -            evaluated by IVUS.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0510 -             ..
PH0511 -        4.  The REVERSAL trial compared the high-dose statin therapy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0512 -            with a conventional, less-potent statin regimen.  During 18                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0513 -            months of treatment, patients treated with the conventional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0514 -            regimen exhibited statistically significant progression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0515 -            atheroma volume (+ 2.7%), despite achieving average                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0516 -            LDL-cholesterol levels of 2.8 mmol/l (110 mg/dl) which was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0517 -            close to the then-current Adult Treatment Panel III goal.69                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0519 -             ..
PH0520 -        5.  By contrast, the high-dose statin group experienced no                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0521 -            significant progression of atheroma volume (average                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0522 -            LDL-cholesterol level, 2 mmol/l [79 mg/dl]).  Importantly,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0523 -            analysis across the treatment groups found that LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0524 -            reduction exceeding approximately 50% was associated with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0525 -            decrease in atheroma volume.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0527 -             ..
PH0528 -        6.  In ASTEROID all patients received the same high-dose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0529 -            therapy for 24 months and pretreatment and post-treatment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0530 -            IVUS findings were compared.  During treatment, LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0531 -            cholesterol dropped to an average of 1.6 mmol/l (60.8                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0532 -            mg/dl), and atheroma volume shrank by a median of 6.8%.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0534 -             ..
PH0535 -        7.  Hence, in both of these studies, extensive LDL-cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0536 -            lowering over an extended period caused established plaques                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0537 -            to shrink.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0539 -             ..
PH0540 -        8.  The greater efficacy seen in ASTEROID could be explained by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0541 -            the lower median LDL-cholesterol level, but also by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0542 -            longer treatment period and higher HDL cholesterol levels                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0543 -            achieved in this study than in REVERSAL.  As in earlier                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0544 -            angiographic studies, we believe that these reductions in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0545 -            plaque volume are accompanied by favorable alterations in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0546 -            plaque biology, a theory which is further supported by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0547 -            evidence that robust plasma LDL lowering to 1.0-1.6 mmol/l                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0548 -            or below (less than or equal to 40-60 mg/dl) is associated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0549 -            with further reductions in cardiovascular events.70                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0551 -  ..
PH0552 - This study does not report side effects taking Rosuvastatin; how many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0553 - patients had to stop the statin to achieve published results.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0555 -  ..
PH0556 - There is no report in this study on side effects of lowering                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0557 - cholesterol, per se, despite its essential role to sustain human life,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0558 - reported above. ref SDS 0 VP5H and ref SDS 0 VT8L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0560 -  ..
PH0561 - Cholesterol aids digestion, memory, and immunity, reported in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0562 - connection with guidelines recently released by the American Heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0563 - Association AHA, shown in the record on 131112 1422. ref SDS 42 NF9H                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PH0564 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0566 -  ..
PH0567 - Rapid Regression Atherosclorotic Plaques Elevated HDL and EPCs                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0568 - Regression Atherosclerosis Plaque Caused By Elevation HDL and Lower LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PH0569 - HDL Elevation and Lower LDL Could Cause Rapid Atherosclerosis Plaque Regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0570 - Atherosclerosis Plaque Regression Caused By HDL Elevation and Lower LDL Could                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0571 - 
PH0572 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0573 - Rapid regression atherosclerosis article continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0574 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0575 -        9.  APOB-LIPOPROTEINS AND FUNCTIONAL HDL IN ATHEROMATA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0576 -            REGRESSION IN HUMANS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0578 -             ..
PH0579 -            To date, human vessel-wall imaging studies suggest that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0580 -            intensive lowering of plasma LDL-cholesterol concentrations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0581 -            concomitant with elevation of functional HDL-cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0582 -            levels could achieve rapid plaque regression.  This                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0583 -            hypothesis is consistent with well-established                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0584 -            epidemiology, the earlier intervention trials that show a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0585 -            positive correlation between clinical end points and low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0586 -            LDL and high HDL levels, a recent meta-analysis of IVUS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0587 -            trial data82 and our recent, aforementioned, experimental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0588 -            studies in mice.  Furthermore, these strategies reduce                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0589 -            cardiovascular events in at-risk subjects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0590 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0591 -               [...below on 131125 0005 another article presents HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0592 -               and endothelium repair as driving regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0593 -               atherosclerosis. ref SDS 0 Z49G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0595 -                ..
PH0596 -               [...below on 131125 0005 article reports small study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0597 -               finding statin treatment for 12 months with Atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0598 -               80 mg combined with ezetimibe 10 mg resulted in 0.4%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0599 -               regression of atherosclerosis plaques. ref SDS 0 Z56P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0601 -  ..
PH0602 - This protocol to lower LDL and increase HDL seems conflicting or at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0603 - least incomplete compared with research above that arterialslerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0604 - occurs from small, dense LDL particles that are cholesterol depleted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0605 - and triglyceride rich, i.e., they are small and dense because they are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0606 - cholesterol depleted, and they are cholesterol depleted because they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0607 - are triglyceride rich, and they are triglyceride rich, because                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0608 - patients are overweight, and do not exercise enough to burn off                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0609 - tryglycerides. (see Doc's opinion written and edited by Axel F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0610 - Sigurdsson, ref SDS 0 M95O; as well, see Doctor Attia's article.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0611 - ref SDS 0 JT6K)  Thus, this article might be more helpful to clarify                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0612 - the prescription of...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0613 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0614 -            ...intensive lowering of plasma LDL-cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PH0615 -            concentrations...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0616 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0617 - ...to say something like...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PH0618 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0619 -            ...intensive lowering of plasma LDL-cholesterol "particle"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0620 -            concentrations...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0621 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0622 - ...thus differentiating LDL-C from LDL-P, per Attia's article                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0623 - presented above. ref SDS 0 FI3G  It may be that he authors intend the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0624 - formulation "LDL-cholesterol concentrations" to simply state in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0625 - another way "LDL particle concentrations", but that is not clear in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0626 - the article.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0628 -  ..
PH0629 - Rapid regression atherosclerosis article continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0630 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0631 -       10.  THE RESOLVING PLAQUE: RAPID STABILIZATION AND REGRESSION                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0632 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0633 -            The key initiating event in atherosclerosis is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0634 -            retention, or trapping, of cholesterol-rich lipoproteins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0635 -            within the arterial wall.15, 83, 84                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0637 -             ..
PH0638 -            The retained lipoproteins become modified, particularly by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0639 -            local enzymes, and they provoke a series of responses that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0640 -            can account for all known features of this disease,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0641 -            including endothelial dysfunction and the development of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0642 -            the lipid-rich, vulnerable plaque.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0644 -             ..
PH0645 -            Recruitment of macrophages into early-stage lesions could                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0646 -            enable phagocytosis and disposal of small quantities of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0647 -            retained lipoproteins.  Our recent work indicates that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0648 -            downstream products of retained and modified lipoproteins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0649 -            are particularly dangerous because they eventually block                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0650 -            the normal emigration of monocyte-derived cells (i.e.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0651 -            macrophages, dendritic cells) from the plaque, thereby                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0652 -            accelerating disease progression.44, 47 These cells then                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0653 -            become abnormally persistent within the lesion and exhibit                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0654 -            a series of strikingly maladaptive responses that include                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0655 -            the secretion of lipases, which greatly accelerate further                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0656 -            lipoprotein retention and modification,85, 86 proteases,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0657 -            which weaken the overlying fibrous cap,87 and tissue                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0658 -            factor, which ensures vigorous clot formation upon plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0659 -            rupture (Figure 2).88                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0661 -  ..
PH0662 - What causes plaque "rupture" mentioned in last sentence of this para?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0663 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0664 -       11.  These data imply a simple model for plaque regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0665 -            (Figure 2).  Major reduction in plasma apoB-lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0666 -            concentrations slows further entry and retention within the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0667 -            arterial wall.  Major enhancement of reverse lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0668 -            transport [...HDL...??] removes cellular but also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0669 -            extracellular lipid deposits.  An early change seen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0670 -            following these environmental changes is restoration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0671 -            normal endothelial function.18, 94, 95                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0673 -             ..
PH0674 -       12.  We hypothesize that at some point, lipoprotein-derived                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0675 -            lipids that had been blocking monocyte-derived cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0676 -            emigration become scarce enough to enable monocytes to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0677 -            leave the plaque, via a process resembling dendritic cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0678 -            emigration.  The emigrating cells take with them their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0679 -            intracellular lipid, and their potential for secretion of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0680 -            unhelpful lipases, proteases and tissue factor.44, 45                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0681 -            Removal of necrotic debris, calcifications and fibrosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0682 -            also occurs,6, 10, 43, 66 facilitated, in theory, by new,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0683 -            normally functioning macrophages (i.e. they enter the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0684 -            regressing plaque, phagocytose and digest what they can,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0685 -            and donate exchangeable material to acceptor lipoproteins,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0686 -            but then leave).14, 96 Our study group18, 44, 45 and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0687 -            others30 have shown that these processes can occur                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0688 -            surprisingly rapidly.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0690 -             ..
PH0691 -       13.  CONCLUSIONS AND FUTURE DIRECTIONS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0692 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0693 -            For regression of atheromata to become a realistic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PH0694 -            therapeutic goal, clinical practitioners must be provided                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0695 -            with tools that extensively change plasma lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0696 -            concentrations and plaque biology while avoiding adverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0697 -            effects.  To date, the animal and human studies that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0698 -            achieved clear-cut plaque regression required large                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0699 -            reductions in plasma levels of apoB-lipoproteins, sometimes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0700 -            combined with brisk enhancements in reverse lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0701 -            transport.  Agents to lower plasma apoB-lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PH0702 -            concentrations include statins and cholesterol-absorption                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0703 -            inhibitors.  Although these two classes of agents have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0704 -            proven safe in widespread clinical use, most patients will                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0705 -            not achieve and sustain the dramatically low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0706 -            LDL-cholesterol levels seen in chow-fed nonhuman                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PH0707 -            primates.97 Efforts to explore other strategies that lower                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0708 -            apoB-lipoprotein levels are underway,98, 99 but progress                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0709 -            may be difficult because of potential adverse effects or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0710 -            inconvenient modes of administration.  Experimental agents                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0711 -            designed to accelerate reverse lipid transport from plaques                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0712 -            into the liver include PC liposomes, apoA-I/PC complexes,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0713 -            apoA-I mimetic peptides, and two remaining CETP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PH0714 -            inhibitors.15, 100, 101 These experimental agents are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0715 -            either in clinical trials or preclinical testing.15, 81,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0716 -            101 An extracorporeal device that delipidates HDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PH0717 -            returns the unloaded particles to the circulation is also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0718 -            undergoing testing.81 Besides the CETP inhibitors, other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0719 -            orally administered small molecules have been investigated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0720 -            preclinically for their potential to enhance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0721 -            HDL-cholesterol levels and reverse lipid transport, such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0722 -            agonists for LXR and peroxisome proliferator-activated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0723 -            receptors.81                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PH0724 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0726 -  ..
PH0727 - Regression Arterialsclorosis Plaque Occurs Lower LDL-P Increased HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0728 - 
PH0729 - This explanation seems to align with the Russert case of low LDL, but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0730 - also very low HDL, i.e., statins lower LDL to target, but do not raise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PH0731 - HDL, and likely not LDL-P, since HDL was low and triglycerides likely                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0732 - high due to metabolic syndrome (overweight).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0734 -             ..
PH0735 -       14.  On the basis of experimental data summarized above, we                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0736 -            expect that the best regression results will be observed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0737 -            when plasma LDL-cholesterol concentrations are reduced and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0738 -            HDL function in reverse lipid transport is enhanced.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0739 -            Additional strategies, such as specific induction of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0740 -            pro-emigrant molecules to provoke the emigration of foam                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0741 -            cells from the arterial wall, should also attract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0742 -            pharmaceutical interest.  Rapid stabilization and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0743 -            regression of established plaques occurs in experimental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PH0744 -            settings in animals and humans, and we should know shortly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PH0745 -            whether plaque regression is within our grasp in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0746 -            broader clinical setting as well.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PH0748 -  ..
PH0749 - Seems like the author's expectation in 2007, when this article was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PH0750 - published, per above, ref SDS 0 KU6J, that clinical interventions to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PH0751 - reduce plaque buildup from arterialsclorosis would become evident                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0752 - "shortly," would be manifest in published studies in the past few                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PH0753 - years, now 7 years later.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PH0754 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0755 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0756 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH0757 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PH08 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0401 -  ..
PI0402 - Prevention Reversal Atherosclerosis Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0403 - Regression Atherosclerosis Plaque Prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0404 - Atherosclerosis Regression Plaque Prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0405 - 
PI0406 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0407 - This is another article...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0408 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0409 -   20.  PMC US National Library of Medicine                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0410 -        National Institutes of Health (NIH)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0411 -        Dovepress Vascular Health and Risk Management                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0413 -         ..
PI0414 -        The prevention and regression of atherosclerotic plaques: emerging treatments                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0415 -        
PI0416 -        by:  Atul Ashok Kalanuria,1 Paul Nyquist,1 and Geoffrey Ling1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0418 -         ..
PI0419 -        Published online........................ 2012 September 25                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0420 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0421 -              http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459726/#b28-vhrm-8-549                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0422 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0423 -        1Division of Neuro Critical Care, Department of Anesthesiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0424 -        and Critical Care Medicine, The Johns Hopkins University                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0425 -        School of Medicine, Baltimore                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0426 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0427 -        2Department of Neurology, Uniformed Services University of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0428 -        Health Sciences, Bethesda, MD, USA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PI0430 -         ..
PI0431 -        Correspondence: Geoffrey Ling, Medical Corps, US Army,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0432 -        Uniformed Services University of the Health Sciences, 4301                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0433 -        Jones Bridge Road, Bethesda, MD 20814, USA, Tel +1 301 295                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0434 -        3643, Fax +1 301 295 0620, Email akalanu1@jhmi.edu                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PI0436 -             ..
PI0437 -        1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0438 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0439 -            Occlusive vascular diseases, such as sudden coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0440 -            syndromes, stroke, and peripheral arterial disease, are a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0441 -            huge burden on the health care systems of developed and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0442 -            developing countries.  Tremendous advances have been made                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0443 -            over the last few decades in the diagnosis and treatment of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0444 -            atherosclerotic diseases.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0446 -             ..
PI0447 -            Intravascular ultrasound has been able to provide detailed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0448 -            information of plaque anatomy and has been used in several                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0449 -            studies to assess outcomes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0451 -             ..
PI0452 -            The presence of atherosclerosis disrupts the normal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0453 -            protective mechanism provided by the endothelium and this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0454 -            mechanism has been implicated in the pathophysiology of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0455 -            coronary artery disease and stroke.  Efforts are being put                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0456 -            into the prevention of atherosclerosis, which has been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0457 -            shown to begin in childhood.  This paper reviews the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0458 -            pathophysiology of atherosclerosis and discusses the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0459 -            current options available for the prevention and reversal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0460 -            of plaque formation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0462 -             ..
PI0463 -        2.  Introduction.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PI0464 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0465 -            According to the 2012 American Heart Association (AHA)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0466 -            statistical update, every year, approximately 795,000                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0467 -            people experience a new or recurrent stroke.  Stroke                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0468 -            accounts for about one of every 18 deaths in the USA, with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0469 -            a stroke occurring every 40 seconds, and is a major cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0470 -            of disability in the elderly.1 Although death rates from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0471 -            cardiovascular diseases (CVDs) have declined, the burden of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0472 -            disease remains high.  An estimated 82.6 million American                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0473 -            adults have vascular disease, with coronary heart disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0474 -            (CHD) and stroke accounting for 16.3 and 7 million,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0475 -            respectively.  Mortality data show that CVD accounted for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0476 -            32.8% of all deaths in 2008, or one of every three deaths                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0477 -            in the USA.  The total direct and indirect cost of CVD and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0478 -            stroke in the USA for 2008 is estimated to be USD$297.7                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0479 -            billion.1 The AHA has put forth a goal to improve                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0480 -            cardiovascular health in the USA by 2020 by reducing deaths                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0481 -            from CVD and stroke by 20%.  By 2030, the AHA estimates                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0482 -            that 40.5% of the US population will have some form of CVD,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0483 -            with direct costs estimated at USD$818 billion.2 Effective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0484 -            prevention strategies are needed if the growing burden of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0485 -            CVD is to be arrested.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0487 -             ..
PI0488 -        3.  Brief pathophysiology of atherosclerosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0489 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0490 -            Atherosclerosis is a multifactorial, multistep disease that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0491 -            involves chronic inflammation from initiation to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0492 -            progression.  All the risk factors contribute to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0493 -            pathogenesis by aggravating the underlying inflammatory                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0494 -            process.3 Destruction of endothelium leads to loss of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0495 -            antithrombic and fibrinolytic factors and nitrous oxide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0496 -            (NO), an increase in the production of vasoconstrictors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0497 -            (thromboxane A2 and prostaglandins), and an increase in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0498 -            intracellular calcium-derived vasoconstricting factors.3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0499 -            Endothelial damage also causes platelets to aggregate at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0500 -            damaged sites, causing monocytes to enter the intima and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0501 -            proliferate.  Intracellular lipid peroxidation leads to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0502 -            formation of lipoperoxides, which are toxic to plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0503 -            membranes and combine with apolipoprotein (apo) B and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0504 -            phospholipids to prevent low-density lipoprotein (LDL) from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0505 -            binding to the LDL receptor.  LDL is oxidized and acts as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0506 -            an attractant to macrophages and monocytes.  Macrophages                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0507 -            ingest LDL and become foam cells, while monocyte mobility                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0508 -            is hampered.  Several other mechanisms have been implicated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0509 -            in the formation of atheromatous plaques, including                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0510 -            imbalance between the coagulation cascade and fibrinolytic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0511 -            systems, accumulation of free radicals, certain infections                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0512 -            and leukocytes and adhesion molecules.3 Elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0513 -            homocysteine in blood leads to thrombosis, intimal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0514 -            thickening, generation of free radicals, and alteration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0515 -            the methylation status of genes.3,4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0517 -             ..
PI0518 -        4.  Role of nitrous oxide NO                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0519 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0520 -            Nitrous oxide and prostacyclin mediate vasodilatation of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0521 -            the endothelium.5 Nitric oxide (NO) is synthesized from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0522 -            the amino acid L-arginine in endothelial cells by nitric                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0523 -            oxide synthase (NOS), which maintains vascular homeostasis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0524 -            by modulation of vascular dilator tone, regulation of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0525 -            local cell growth, and protection of the vessel from the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0526 -            injurious consequences of platelets and cells circulating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0527 -            in the blood.6 Conversion of angiotensin I to angiotensin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0528 -            II also acts as a vasoconstrictor, modulating the effect                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0529 -            of the vasododilators.5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0531 -             ..
PI0532 -        5.  Disruption of protective mechanisms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0533 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0534 -            Development of atherosclerosis leads to the disruption of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0535 -            the mentioned protective mechanisms inherent to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0536 -            endothelium and causes the formation of plaque and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0537 -            thrombosis.  Coronary artery occlusion is the direct effect                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0538 -            of thrombus formation on ruptured and unruptured plaques at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0539 -            the site of atherosclerosis and is responsible for 60%?80%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0540 -            of acute coronary syndrome (ACS) cases.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0541 -            Inflammation-mediated neovascularization and intra-plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0542 -            hemorrhage, along with necrosis in the lipid core, are most                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0543 -            often the cause of thrombogenesis.7 Rarely, genetic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0544 -            disorders like familial lecithin:cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PI0545 -            acyltransferase deficiency and fish-eye disease cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0546 -            low-plasma high-density lipoprotein (HDL) and accumulation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0547 -            of unesterified cholesterol in the body.8                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0549 -             ..
PI0550 -        6.  Role of plaque formation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0551 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0552 -            Atherosclerosis with thrombus formation has been recognized                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0553 -            as a major cause of cardiovascular death.  It begins early                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0554 -            in childhood and progresses in adult life when it can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0555 -            potentially manifest as coronary artery disease (CAD),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0556 -            stroke, and/or peripheral vascular disease.  Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0557 -            formation is favored by a zone of absence of shear stress,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0558 -            which occurs mostly, ref SDS 0 6I3K, at arterial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0559 -            bifurcations.  This is hypothesized to be related to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0560 -            absence of elastin at this location and the presence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0561 -            collagen-proteoglycan complexes, which causes LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0562 -            retention.9 Plaque rupture is the most common cause of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0563 -            arterial thrombosis coronary artery syndrome and is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0564 -            hypothesized to be a common cause of large-vessel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0565 -            atherosclerotic stroke.  Anatomically, a ruptured plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0566 -            contains a large lipid-rich core and a thin fibrous cap                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0567 -            with smooth muscles and macrophages, angiogenesis,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0568 -            adventitial inflammation, and remodeling.10                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0570 -             ..
PI0571 -            In a recent study of 697 patients, plaque morphology was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0572 -            studied in the setting of ACS.  Stone et al evaluated these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0573 -            patients with three vessel angiograms and intravascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0574 -            ultrasound (IVUS) and conducted follow-up for a median of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0575 -            3.4 years.11 Adverse cardiac events occurred in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0576 -            distributions of previously ?non-culprit? areas with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0577 -            fibroatheromas or a large plaque burden.11 Increases in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0578 -            intimal and medial thickness of the carotid artery                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0579 -            (measured by ultrasonography) are directly associated with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0580 -            an increased risk of myocardial infarction and stroke in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0581 -            adults > 65 years old without a history of CVD.12                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0582 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0584 -             ..
PI0585 -        7.  Primary Prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0586 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0587 -            Since atherosclerosis begins in childhood, primary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0588 -            prevention must begin as early as possible. To this end,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0589 -            screening, risk-factor reduction, and appropriate use of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0590 -            primary prevention medications are now being applied to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0591 -            children. The 2003 AHA guidelines for primary prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0592 -            of atherosclerosis beginning in childhood recommend that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0593 -            children older than 2 years with a family history of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0594 -            hyperlipidemia or premature cardiac disease should have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0595 -            targeted screening of fasting lipids. Concern should be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0596 -            raised if HDL levels are <35 mg/dL, total cholesterol is
PI0597 -            borderline (> 170 mg/dL) or elevated (>200 mg/dL),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0598 -            low-density-lipoprotein cholesterol (LDL-C) is borderline                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0599 -            (>110 mg/dL) or elevated (>130 mg/dL) or triglycerides are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0600 -            >150 mg/dL. Screening is also recommended if family                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0601 -            history is unknown or other risk factors are present.13                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0602 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0604 -  ..
PI0605 - Atherosclerosis Test Imaging Intravascular Ultrasound IVUS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0606 - IVUS Intravascular Ultrasound Atherosclerosis Test Imaging                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0607 - Atherosclerosis Test Imaging Carotid Artery Intimal-Medial Thickness CIMT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0608 - CIMT Carotid Artery Intimal-Medial Thickness Atherosclerosis Test Imaging                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0609 - 
PI0611 -             ..
PI0612 -            The 2010 American College of Cardiology Foundation/AHA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0613 -            guidelines recommend measurement of carotid artery                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0614 -            intimal-medial thickness (CIMT) for cardiovascular risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0615 -            assessment in asymptomatic adults at intermediate risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0616 -            (Class IIa recommendation, level of evidence: B).14                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0618 -             ..
PI0619 -        8.  Role of screening tools                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0620 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0621 -            Recently, in a National Institutes of Health-sponsored                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0622 -            multi-ethnic study conducted to validate imaging for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0623 -            primary prevention of atherosclerosis, Zeb and Budoff                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0624 -            showed that coronary artery calcium scores and CIMT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0625 -            evaluation are validated as a marker of atherosclerosis.16                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0626 -            Current national guidelines recommend using coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0627 -            artery calcium as a screening tool for risk stratification                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0628 -            of intermediate-risk (10%-20% 10-year risk), asymptomatic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0629 -            population (Class IIa recommendation), and low- to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0630 -            intermediate-risk populations (6%-10% 10-year risk; level                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0631 -            of evidence: B).14,16                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0633 -             ..
PI0634 -            The Screening for Heart Attack Prevention and Education                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0635 -            (SHAPE) task force conducted noninvasive screening of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0636 -            asymptomatic men aged 45-75 years and asymptomatic women                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0637 -            aged 55-75 years. The primary goal was to detect and treat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0638 -            all those with subclinical atherosclerosis except those                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0639 -            considered very low risk. In addition to screening for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0640 -            risk-factor assessment (lifestyle, family history, blood                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0641 -            pressure, diabetes, hyperlipidemia, etc), the authors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0642 -            advocate additional arterial structure testing, such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0643 -            carotid ultrasound, coronary calcium score by computed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0644 -            tomography (CT) imaging, cardiac and aortic magnetic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0645 -            resonance imaging (MRI), and ankle-brachial index.17                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0646 -            Additional arterial function testing, such as ultrasound                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0647 -            brachial vasoreactivity, as well as radial and fingertip                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0648 -            tonometry, can also be considered.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0650 -             ..
PI0651 -            In an observational study of 1118 Spanish patients over 30                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0652 -            years of age, Aguilar-Shea et al identified 320 subjects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0653 -            as low-intermediate cardiovascular risk using the European                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0654 -            Systematic Coronary Risk Evaluation (SCORE).18 After                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0655 -            B-mode ultrasound, 18.4% of the subjects were reclassified                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0656 -            to the high-risk category, suggesting that CIMT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0657 -            measurement could be a useful preventive tool.18                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0659 -             ..
PI0660 -            An article by Hecht has further stressed the importance of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0661 -            imaging modalities in the primary prevention of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0662 -            atherosclerosis.19 Indeed, a focused analysis of vascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0663 -            anatomy often leads to the recategorizing of the risk of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0664 -            asymptomatic individuals irrespective of their cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0665 -            levels.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0667 -             ..
PI0668 -        9.  Role of antioxidants                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0669 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0670 -            In recent years, there has been significant discussion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0671 -            about antioxidants and their possible role in prevention of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0672 -            atherosclerosis.  The antioxidant market is a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PI0673 -            multi-billion-dollar industry, but there are no randomized                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0674 -            clinical studies providing support that they are of benefit                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0675 -            in the prevention of CVD.22                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0677 -             ..
PI0678 -            [...rest of this section omitted...]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0680 -             ..
PI0681 -       10.  Role of diet                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PI0682 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0683 -            The American heart Association provides recommendations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0684 -            for diet and lifestyle modifications (Table 1). The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0685 -            importance of diet in cardiovascular health has been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0686 -            summarized by Dauchet et al.25 As noted in their review,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0687 -            most of the evidence supporting the cardio protective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0688 -            properties of fruits and vegetables is based on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0689 -            observational epidemiological studies, which have reported                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0690 -            either weak or associations of low significance.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0692 -             ..
PI0693 -            [...rest of this section omitted...]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0695 -  ..
PI0696 - Exercise Vigorous 150 Minutes Moderate 75 Minutes Per Week - AHA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0697 - 
PI0698 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0699 -       11.  Role of exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0700 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0701 -            It is now well accepted that a sedentary lifestyle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0702 -            increases the risk of atherosclerosis.  The AHA guidelines                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0703 -            recommend at least 150 minutes per week of moderate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0704 -            exercise or 75 minutes per week of vigorous exercise or a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0705 -            combination of moderate and vigorous activity.  There are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0706 -            several mechanisms by which exercise promotes protection                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0707 -            against atherosclerosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0709 -             ..
PI0710 -            Exercise reduces or prevents oxidative stress and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0711 -            inflammation through downregulation of endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0712 -            angiotensin II type 1 receptor expression.  This leads to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0713 -            decreases in nicotinamide adenine dinucleotide                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PI0714 -            phosphate-oxidase activity and superoxide anion production,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0715 -            which in turn decreases reactive oxygen species generation,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0716 -            preservation of endothelial NO bioavailability and its                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0717 -            protective anti-atherogenic effects.  This is caused by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0718 -            endothelial activation from laminar shear stress.  Skeletal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0719 -            muscle contraction releases anti-inflammatory cytokines,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0720 -            such as interleukin-6, which inhibits tumor necrosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0721 -            factor-alpha production in adipose tissue and macrophages.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0723 -  ..
PI0724 - Weight Loss Increases HDL Lowers Blood Pressure Aided Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0725 - Exercise Weight Loss Aids HDL Increase and Lowers Blood Pressure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0726 - Exercise Lowers Triglycerides LDL-P Apo B Increases HDl Decrease Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PI0727 - 
PI0728 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0729 -            Exercise-associated weight loss also leads to a lowering of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0730 -            blood pressure, improvement in insulin sensitivity, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0731 -            increased HDL.27 A recent review of several observational                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0732 -            and interventional trials of the effects of physical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0733 -            activity on CVD has found that regular exercise leads to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0734 -            triglyceride reduction, apo B reduction, and HDL increase.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0735 -            In addition, physical activity can also lead to an increase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0736 -            in tissue plasminogen activator activity and a decrease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0737 -            coronary artery calcium.28                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0739 -             ..
PI0740 -            As mentioned, risk-factor assessment is the first step in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0741 -            the primary prevention of atherosclerotic disease. The next                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0742 -            stage of evaluation could include blood tests like lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0743 -            profile as well as new markers like C-reactive protein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0744 -            (CRP), lipoprotein-associated phospholipase A2, LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0745 -            subfraction analysis, apo B/apo A-I ratio, and lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0746 -            A. Assessment of coronary calcification and CIMT contribute                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0747 -            to risk stratification. There is also suggestion that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0748 -            influenza vaccine may have a preventive effect and that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0749 -            gene therapy with genetic subtyping and proteomics may lead                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0750 -            to new preventive clinical insights.29                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0751 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0753 -             ..
PI0754 -       12.  Plaque regression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0755 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0756 -            It is now known that plaques are able to regress.  Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0757 -            reversal occurs by removal of lipids and necrotic material,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0758 -            endothelial repair, or halt of vascular smooth muscle cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0759 -            proliferation.  Several mechanisms explain this reversal,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0760 -            such as high-density lipoprotein cholesterol (HDL-C)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0761 -            action, destruction of foam cells and macrophages in lymph                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0762 -            nodes and restoration of endothelium by neighboring cells                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0763 -            or circulating progenitors.39                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PI0765 -  ..
PI0766 - This representation citing HDL combined with "circulating progenitors"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0767 - to restore endothelium enables regression of atherosclerotic plaques,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0768 - does not say lowering LDL-C, which seems to be presented in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0769 - article above. ref SDS 0 6S7F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0770 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0771 -               [...below on 131125 0005 article reports small study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0772 -               finding statin treatment for 12 months with Atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0773 -               80 mg combined with ezetimibe 10 mg resulted in 0.4%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0774 -               regression of atherosclerosis plaques. ref SDS 0 Z56P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0776 -  ..
PI0777 - Article continues - ...regression of atherosclerotic plaques...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0778 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0779 -       13.  Role of statins, phosphodiesterase inhibitors, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0780 -            thiazolidinediones                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0782 -             ..
PI0783 -            In a recent meta-analysis of eight trials, 919 patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0784 -            (461 patients in the statin group and 458 in the placebo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0785 -            group) were studied with IVUS.40 There was no significant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0786 -            difference between the two groups in terms of their plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0787 -            characteristics at baseline.  However, there was a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0788 -            statistically significant mean difference in coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0789 -            atheroma volume between the statin therapy and the placebo                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0790 -            arms, which was ?3.573 (95% CI ?4.46 to ?2.68; P < 0.01).
PI0791 -            This suggests that statins have the potential to induce                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0792 -            plaque reversal.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0794 -             ..
PI0795 -       14.  One small study analyzed the effects of rosuvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0796 -            combined with ramipril on atheroma volume and its mechanism                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0797 -            in patients with intermediate CAD.41 In this study, 21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0798 -            patients received rosuvastatin (20 mg daily) and 19                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0799 -            patients received rosuvastatin along with ramipril (20 mg                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0800 -            and 10 mg, respectively) for 9 to 12 months.  The study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0801 -            focused on measurement of TAV per 10 mm segment along with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0802 -            lipids, metabolic parameters (adiponectin, insulin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0803 -            sensitivity), and biomarkers (high-sensitivity [hs]-CRP,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0804 -            matrix metalloproteinase-9) at baseline and end of study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0805 -            There was decrease in the TAV in both groups, with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0806 -            reduction in the CRP levels in the combination treatment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0807 -            group.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0809 -             ..
PI0810 -       15.  Takayama and colleagues studied the effect of rosuvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0811 -            on plaque volume on 126 patients with stable CAD on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0812 -            lipid-lowering therapy at 37 centers in a 76-week                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0813 -            open-label study.42 Subjects received rosuvastatin 2.5 mg                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0814 -            per day (with the potential to be increased at 4-week                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0815 -            intervals to up to 20 mg per day).  The primary end point                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0816 -            of percent change of plaque volume, as evaluated by IVUS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0817 -            was ?5.1% ± 14.1% in the rosuvastatin group (P < 0.0001).
PI0819 -             ..
PI0820 -       16.  Hibi et al studied effects of statin treatment on plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0821 -            regression in patients with polyvascular disease versus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0822 -            those with CAD alone.43 They studied 252 patients (at 33                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0823 -            centers) with a history of an ACS, who underwent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PI0824 -            percutaneous intervention to localize the lesion followed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0825 -            by treatment with atorvastatin (20 mg per day) or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0826 -            pitavastatin (4 mg per day). Both groups showed regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0827 -            of plaques, as assessed by IVUS at baseline and at 8?12                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0828 -            months follow-up. A sub-analysis of this study showed that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0829 -            aggressive lipid lowering by pitavastatin and atorvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0830 -            results in marked regression of atherosclerotic coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0831 -            lesions after ACS. The study involved data from 251                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0832 -            patients (73 were diabetic) and the authors studied the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0833 -            association of lipid levels after statin therapy with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0834 -            regression of atherosclerotic coronary lesions and major                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0835 -            cardiovascular events in patients after ACS. The results                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0836 -            showed that decrease in LDL-C, non-HDL-C, LDL-C/HDL-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0837 -            ratio, and apo B levels were all associated with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0838 -            progressively smaller plaque burden. In diabetic patients,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0839 -            further reduction of these parameters was associated with a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0840 -            significantly greater reduction in plaque volume.44                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0842 -             ..
PI0843 -       17.  In a prospective randomized comparative study using                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0844 -            rosuvastatin 20 mg (n = 65) and atorvastatin 40 mg (n =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0845 -            63), IVUS was used at baseline and at 11-month follow-up,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0846 -            to show effective plaque regression. TAV and percent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0847 -            atheroma volume (PAV) was measured. Plaque was decreased in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0848 -            99 of 128 patients (77%; 85% [55/65] in the rosuvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0849 -            group vs 70% [44/63] in the atorvastatin group).  Both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0850 -            groups showed change in TAV: ?4.4 ± 7.3 mm3 for the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0851 -            rosuvastatin group and ? 3.68 ± 6.8 mm3 for the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0852 -            atorvastatin group (P = 0.5). The difference in PAV between                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0853 -            the two groups was not statistically significant (P =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0854 -            0.14). These results demonstrate that both statins are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0855 -            effective in reducing plaque burden.45                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0857 -             ..
PI0858 -       18.  Tani et al studied the effect of pravastatin on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0859 -            atherosclerotic plaque in a 6-month prospective study of 64                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0860 -            patients. Pravastatin reduced plaque volume, as measured by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0861 -            volumetric intravascular ultrasonography, by 12.6% (P <
PI0862 -            0.0001 vs baseline).46 The authors also found a significant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0863 -            reduction in the apoB/apoA-1 ratio (P < 0.0001 vs
PI0864 -            baseline).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0866 -             ..
PI0867 -       19.  The effect of atorvastatin on MRI changes in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PI0868 -            atherosclerotic plaques in the thoracic and abdominal aorta                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0869 -            was studied in a prospective study in which 87 patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0870 -            with hypercholesterolemia were administered either                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0871 -            atorvastatin (n = 42) or atorvastatin plus etidronate (n =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0872 -            47) for 12 months.47 LDL levels and wall thickness in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0873 -            thoracic aorta were reduced in both groups (?15% and ?14%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0874 -            for the combination therapy and monotherapy group,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0875 -            respectively; P < 0.001 vs baseline for both groups).
PI0876 -            However, only patients in the combination group had a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0877 -            reduction in wall thickness of the abdominal aorta (?14%; P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0878 -            < 0.001 vs baseline).
PI0880 -             ..
PI0881 -       20.  The SECURE study was an ongoing Phase IV double-blind                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0882 -            randomized controlled multicenter clinical trial of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0883 -            patients who were given either a combination of cilostazol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0884 -            and probucol or cilostazol alone.48 Plaque volume and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0885 -            composition using IVUS was studied as the primary end point                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0886 -            at baseline and 9-month follow-up. This study has been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0887 -            completed and results are awaited.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0888 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0890 -  ..
PI0891 - Atorvastatin 80 Ezetimibe 10 Yield Atherosclerosis Regression 0.4%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0892 - 
PI0893 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0894 -       21.  Kovarnik et al randomized 89 patients to receive either                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0895 -            atorvastatin 80 mg plus ezetimibe 10 mg or standard                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0896 -            treatment per the patients' general practitioner for 12                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0897 -            months.49 The authors found a decrease in the coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0898 -            artery PAV (-0.4%) in the group on combination treatment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0899 -            versus an increase (+ 1.4%) in the other group (P = 0.014),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0900 -            as measured by IVUS. There was also an increased frequency                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0901 -            of combined atherosclerosis regression (increased lumen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0902 -            volume plus decreased PAV) in patients taking both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0903 -            medications (40.5%) compared with the group on monotherapy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0904 -            (14.9%) (P = 0.007).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0906 -  ..
PI0907 - Doctor Alba planning treatment trial at VA Medical Center in San                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0908 - Francisco, combining Atorvastatin 10 mg with ezetimibe 10 mg, reported                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0909 - on 131121. ref SDS 44 6H6K  Atorvastatin 10 mg is well below 80 mg                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PI0910 - dose prescribed for the study that seems to report 0.4% regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0911 - atherosclerosis plaques over 1 year, thus indicating regression in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0912 - this case would not be related to drug treatments.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0913 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0914 -               [...above on 131125 0005 article HDL combined with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0915 -               "circulating progenitors" to restore endothelium enables                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0916 -               regression of atherosclerotic plaques, ref SDS 0 Z49G,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0917 -               does not say lowering LDL-C, which seems to be presented                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0918 -               in another article further above. ref SDS 0 6S7F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0920 -  ..
PI0921 - Article continues - ...regression of atherosclerotic plaques...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0922 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0923 -       22.  A recent study used cardiovascular magnetic resonance (MR)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0924 -            to study volumetric carotid plaque measurement on 26                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0925 -            subjects who had carotid plaques greater than 1.1 mm and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0926 -            coronary or cerebrovascular atherosclerotic disease (mean                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0927 -            age 67 ± 2 years, 7 females).50 The subjects underwent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0928 -            evaluation with 3 Tesla MR (T1, T2, proton density, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0929 -            time of flight sequences) and two-dimensional ultrasound at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0930 -            baseline and after 6 months of statin therapy.  Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0931 -            volume as measured by MR decreased by 5.8% ± 2% (1036 ± 59                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0932 -            to 976 ± 65 mm3; P = 0.018) while mean plaque volume, as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0933 -            measured by ultrasound, was unchanged (1.12 ± 0.06 vs 1.14                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0934 -            ± 0.06 mm; P = not significant). Those patients (n = 13)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0935 -            who had an initiation or increase of statins had ?8.8% ±                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0936 -            2.8% change (P = 0.001), as compared with an insignificant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0937 -            change in patients (n = 13) who were on statin maintenance.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0939 -             ..
PI0940 -       23.  Nicholls et al compared serial intravascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PI0941 -            ultrasonography in 1039 patients with coronary disease, at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0942 -            baseline and after 104 weeks of treatment with either                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PI0943 -            atorvastatin, 80 mg daily, or rosuvastatin 40 mg daily.51                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0944 -            In the atorvastatin group, the atheroma volume decreased by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0945 -            0.99% (95% CI ?1.19 to ?0.63) and 1.22% (95% CI -1.52 to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0946 -            -0.90) in rosuvastatin group (P = 0.17). The normalized TAV                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0947 -            was -6.39 mm3 (95% CI, -7.52 to -5.12) with rosuvastatin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0948 -            and -4.42 mm3 (95% CI, -5.98 to -3.26) with atorvastatin (P                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0949 -            = 0.01). The side-effect profiles were acceptable in both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0950 -            groups.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0952 -             ..
PI0953 -       24.  A previous review of four prospective randomized trials                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0954 -            showed significant regression in coronary atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0955 -            associated with the lowering of LDL-C levels and an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0956 -            increase in HDL.52 This post-hoc analysis included 1455                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0957 -            patients with angiographic CAD who underwent serial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PI0958 -            intravascular ultrasonography while receiving statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0959 -            treatment for 18 to 24 months.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PI0961 -             ..
PI0962 -       25.  In their 6-month study, Yang and colleagues studied the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0963 -            effect of pioglitazone on coronary plaque area and plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0964 -            burden in patients with impaired glucose tolerance and CAD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0965 -            who were taking atorvastatin 20 mg daily for 3 months,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PI0966 -            followed by 10 mg daily for the next 3 months.53 At the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0967 -            completion of treatment, they underwent IVUS. Compared with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0968 -            the control group, 6 months' treatment with pioglitazone                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0969 -            significantly decreased coronary plaque burden (50.7 ± 11.1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0970 -            vs 64.1% ± 10.3%; P < 0.05), decreased plaque area (6.22 ±
PI0971 -            2.03 vs 8.31 ± 4.29; P < 0.05), decreased thin-cap
PI0972 -            fibroatheroma prevalence (11% vs 22%; P < 0.05), and
PI0973 -            decreased percentage of necrotic core area (16% ± 8% vs 31%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0974 -            ± 7%; P < 0.05). Incidentally, the patients taking
PI0975 -            pioglitazone had significantly lower hs-CRP and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PI0976 -            endothelin-1 levels and higher adiponectin levels.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0978 -             ..
PI0979 -       26.  Another study of 26 patients evaluated the effect of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0980 -            pioglitazone on coronary plaque structure. IVUS was used to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0981 -            demonstrate that pioglitazone reduced plaque burden without                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0982 -            LDL-C reduction in patients suffering from diabetes and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0983 -            impaired glucose tolerance.54 Thirteen patients received                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0984 -            pioglitazone 15 mg per day for an initial 14 days after                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PI0985 -            percutaneous coronary intervention followed by 30 mg per                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0986 -            day with the remaining patients as control. At the end of 6                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PI0987 -            months, the pioglitazone group had significantly reduced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0988 -            plaque volume (101.3 ± 32.1 to 94.6 ± 33.6 mm3, ?7.2%; P =                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PI0989 -            0.0023). Serum cholesterol levels were also significantly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PI0990 -            improved in the pioglitazone group; they had lower                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PI0991 -            triglyceride and CRP levels and higher HDL levels at the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PI0992 -            end of the study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PI0993 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0994 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0995 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0996 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0997 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI0998 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PI10 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PJ03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0401 -  ..
PJ0402 - Triglycerides Lower Endurance Exercise Increase HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0403 - Endurance Exercise Increase HDL Lowers Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0404 - Exercise HDL Increase Triglyceride Lower Endurance Training                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PJ0405 - HDL Increase Endurance Exercise Lowers Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0406 - 
PJ0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0408 - Another article says...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0410 -        American Heart Association                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0412 -         ..
PJ0413 -        Arteriosclerosis, Thrombosis, and Vascular Biology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PJ0415 -         ..
PJ0416 -        Atherosclerosis and Lipoproteins                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0418 -         ..
PJ0419 -   21.  Effects of Endurance Exercise Training on Plasma HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PJ0420 -        Cholesterol Levels Depend on Levels of Triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PJ0422 -         ..
PJ0423 -        Received January 29, 2001.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0424 -        Accepted April 6, 2001.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0425 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0426 -              http://atvb.ahajournals.org/content/21/7/1226.full                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0428 -         ..
PJ0429 -        Evidence From Men of the Health, Risk Factors, Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0430 -        Training and Genetics (HERITAGE) Family Study                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0432 -         ..
PJ0433 -        Charles Couillard, Jean-Pierre Despr's, Beno't Lamarche,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0434 -        Jean Bergeron, Jacques Gagnon, Arthur S. Leon, DC Rao,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0435 -        James S Skinner, Jack H Wilmore, Claude Bouchard                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0436 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0437 -            From the Lipid Research Center (C.C., J.-P.D., B.L., J.B.)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0438 -            and the Laboratory of Molecular Endocrinology (J.G.),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0439 -            Laval University Medical Research Center, CHUL Pavilion,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0440 -            Sainte-Foy, Québec, Canada; the Physical Activity Sciences                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0441 -            Laboratory (J.G.), Department of Kinesiology, and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0442 -            Department of Food Sciences and Nutrition (J.-P.D., B.L.),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0443 -            Laval University, Sainte-Foy, Québec, Canada; the Québec                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0444 -            Heart Institute (J.-P.D.), Laval Hospital Research Center,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0445 -            Sainte-Foy, Québec, Canada; the School of Kinesiology and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0446 -            Leisure Studies (A.S.L.), University of Minnesota,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0447 -            Minneapolis; the Division of Biostatistics (D.C.R.),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0448 -            Washington University Medical School, St. Louis, Mo; the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0449 -            Department of Kinesiology (J.S.S.), Indiana University,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0450 -            Bloomington; the Department of Health and Kinesiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0451 -            (J.H.W.), Texas A&M University, College Station; and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0452 -            Pennington Biomedical Research Center (C.B.), Louisiana                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0453 -            State University, Baton Rouge.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PJ0455 -         ..
PJ0456 -        Correspondence to Jean-Pierre Despr's, PhD, Quebec Heart                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0457 -        Institute, Pavilion Mallet, 2nd Floor, 2725 chemin Sainte-Foy,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0458 -        Sainte-Foy, Quebec, Canada G1V 4G5. E-mail                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0459 -        Jean-Pierre.Despres@crchul.ulaval.ca                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PJ0460 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0461 -        1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0462 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0463 -            High density lipoprotein (HDL) cholesterol concentrations                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0464 -            have been shown to increase with regular endurance exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0465 -            and, therefore, can contribute to a lower risk of coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0466 -            heart disease in physically active individuals compared                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0467 -            with sedentary subjects.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0469 -  ..
PJ0470 - Hypoalphalipoproteinemia - Low HDL < 35
PJ0471 - 
PJ0472 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0473 -        2.  Although low HDL cholesterol levels are frequently observed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0474 -            in combination with hypertriglyceridemia [...triglycerides                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0475 -            elevated above 150...], some individuals may be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PJ0476 -            characterized by isolated hypoalphalipoproteinemia, ie, low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0477 -            HDL cholesterol levels in the absence of elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PJ0478 -            triglyceride (TG) concentrations.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PJ0480 -  ..
PJ0481 - Low HDL and low triglycerides seems evident in patient history for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0482 - lipid profile the past 9 years, reported on 140203 1147. ref SDS 54                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PJ0483 - W25L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0485 -  ..
PJ0486 - AHA Article Published January 29, 2001 continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0487 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0488 -        3.  The present study compared the responses of numerous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0489 -            lipoprotein-lipid variables to a 20-week endurance exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0490 -            training program in men categorized on the basis of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0491 -            baseline TG and HDL cholesterol concentrations: (1) low TG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0492 -            and high HDL cholesterol (normolipidemia), (2) low TG and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0493 -            low HDL cholesterol (isolated low HDL cholesterol), (3)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0494 -            high TG and high HDL cholesterol (isolated high TGs), and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0495 -            (4) high TGs and low HDL cholesterol (high TG/low HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0496 -            cholesterol).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PJ0498 -             ..
PJ0499 -        4.  A series of physical and metabolic variables was measured                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0500 -            before and after the training program in a sample of 200                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0501 -            men enrolled in the Health, Risk Factors, Exercise Training                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0502 -            and Genetics (HERITAGE) Family Study.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0504 -             ..
PJ0505 -        5.  At baseline, men with high TG/low HDL cholesterol had more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0506 -            visceral adipose tissue than did men with isolated low HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0507 -            cholesterol and men with normolipidemia.  The 0.4% (not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0508 -            significant) exercise-induced increase in HDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0509 -            levels in men with isolated low HDL cholesterol suggests                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0510 -            that they did not benefit from the "HDL-raising" effect of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0511 -            exercise.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0513 -             ..
PJ0514 -        6.  In contrast, men with high TG/low HDL cholesterol showed a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0515 -            significant increase in HDL cholesterol levels (4.9%,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0516 -            P<0.005).  Whereas both subgroups of men with elevated TG
PJ0517 -            levels showed reductions in plasma TGs (??15.0%, P<0.005),
PJ0518 -            only those with high TG/low HDL cholesterol showed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0519 -            significantly reduced apolipoprotein B levels at the end of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0520 -            the study (?6.0%, P<0.005).
PJ0522 -             ..
PJ0523 -        7.  Multiple regression analyses revealed that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PJ0524 -            exercise-induced change in abdominal subcutaneous adipose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0525 -            tissue [... fat ...] (10.6%, P<0.01) was the only
PJ0526 -            significant correlate of the increase in plasma HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0527 -            cholesterol with training in men with high TG/low HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0528 -            cholesterol.  Results of the present study suggest that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0529 -            regular endurance exercise training may be particularly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0530 -            helpful in men with low HDL cholesterol, elevated TGs, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0531 -            abdominal obesity.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0533 -             ..
PJ0534 -        8.  Endurance Exercise Training Program                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0535 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0536 -            Participants trained under supervision in the clinical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0537 -            centers on a cycle ergometer (Universal Aerobicycle) for 60                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0538 -            sessions by using the same standardized training protocol.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0539 -            They were required to complete the 60 sessions within 21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0540 -            weeks.  They could not exercise >1 session per day, >4                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0541 -            sessions per week, or <1 session per week.
PJ0543 -  ..
PJ0544 - This study tested patients for endurance exercise using a stationary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0545 - bicycle - Universal Aerobicycld...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0546 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0547 -              http://www.shopwiki.com/l/universal-aerobicycle-upright-stationary-exercise-bikes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0549 -  ..
PJ0550 - AHA Article Published January 29, 2001 continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0551 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0552 -        9.  Training sessions during the first 2 weeks began at an HR                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0553 -            associated with 55% VO2max for 30 minutes. Either duration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0554 -            or intensity was then increased each 2 weeks until the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0555 -            14th week of training, when participants exercised at the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0556 -            HR associated with 75% of their initial VO2max for 50                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0557 -            minutes. This was then maintained for the next 6 weeks.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0559 -  ..
PJ0560 - Training 3 - 4 days per week for 50 minutes does not seem like                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0561 - "endurance" training.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0563 -  ..
PJ0564 - The critical factor is level of effort.  Longer distances and higher                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0565 - speeds for longer periods increases results at low initial levels.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0567 -  ..
PJ0568 - How would this compare to training 6 days per week for 180 minutes per                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0569 - session?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PJ0570 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0572 -  ..
PJ0573 - HDL Low Biggest Risk CVD CAD Heart Attack                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PJ0574 - VA HDL Intervention Study Found HDL Strongest Protection Against CVD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0575 - 
PJ0576 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0577 -       10.  It is well established that low plasma HDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0578 -            levels are associated with an increased risk of CHD.33 34                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0579 -            Indeed, a low HDL cholesterol concentration has been shown                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0580 -            to be the most prevalent abnormality of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0581 -            lipoprotein-lipid profile reported among men with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PJ0582 -            documented CHD.35 In this regard, the recently published                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0583 -            results of the Veterans Affairs High-Density Lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0584 -            Intervention Trail (VA-HIT) Study36 clearly show that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0585 -            pharmacotherapy aimed at increasing plasma HDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0586 -            levels reduces the risk of CHD, even in the absence of any                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0587 -            change in plasma LDL cholesterol levels; this latter                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0588 -            finding is commonly observed when CHD patients with low HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0589 -            cholesterol levels are treated with a fibrate such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0590 -            gemfibrozil.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0592 -  ..
PJ0593 - This finding aligns with patient profile history showing relatively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0594 - low triglycerides, but also low HDL with LDL not excessively elevated.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0595 - 140203 1147, ref SDS 54 W25L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0597 -  ..
PJ0598 - The factor in this case seems to be weight control.  For most of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0599 - time from 2006 until CABG +4 surgery on 091022, patient weighed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0600 - 200-210.  On or about August/July 2009 patient suddenly lost about 30                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0601 - pounds over a period of 2 months, due to accumulated effects of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0602 - achalasia (swallowing problems).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0604 -  ..
PJ0605 - AHA Article Published January 29, 2001 continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0606 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0607 -       11.  It is now fairly well recognized that endurance exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0608 -            training can increase plasma HDL cholesterol levels1 2 3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0609 -            if the exercise training stimulus is sufficient.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PJ0611 -             ..
PJ0612 -       12.  Furthermore, several studies have suggested that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0613 -            HDL-raising effect of endurance exercise training could be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0614 -            largely explained by the concomitant loss of body mass or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0615 -            fat.37                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0617 -             ..
PJ0618 -       13.  Therefore, among high-risk overweight dyslipidemic patients                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0619 -            with insulin resistance, hyperinsulinemia,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0620 -            hypertriglyceridemia, and low HDL cholesterol levels, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0621 -            net increase in the daily energy expenditure produced by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0622 -            regular endurance exercise may eventually induce                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PJ0623 -            mobilization of body fat and weight loss.  In turn, this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0624 -            may ultimately reduce the amount of abdominal fat, improve                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0625 -            insulin action, lower TG levels, and increase plasma HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0626 -            cholesterol concentrations.38 These favorable metabolic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0627 -            improvements explain why regular endurance exercise of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0628 -            moderate intensity but of long duration is advocated for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0629 -            the management of obesity and of its related high TG/low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0630 -            HDL cholesterol dyslipidemia.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PJ0632 -  ..
PJ0633 - Exercise protocol for reducing weight, lowering triglycerides, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0634 - raising HDL is low intensity for long duration.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0636 -  ..
PJ0637 - Hiking 3 - 4 hours (11 - 15 miles) per day for 7 days meets this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0638 - criteria.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PJ0640 -             ..
PJ0641 -       14.  However, low plasma HDL cholesterol is a heterogeneous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0642 -            condition.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0644 -             ..
PJ0645 -            Apart from rare monogenic disorders,39 40 41 it is not                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0646 -            uncommon to find individuals with low HDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0647 -            levels in the absence of abdominal obesity, insulin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PJ0648 -            resistance, or hypertriglyceridemia.  For instance, in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0649 -            present study, 38 men of the total sample of 200 men (19%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0650 -            of the sample) had plasma HDL cholesterol levels <0.92
PJ0651 -            mmol/L, while simultaneously having plasma TG levels <1.34
PJ0652 -            mmol/L.  This group with isolated low HDL cholesterol had                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0653 -            very low average plasma cholesterol as well as LDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0654 -            cholesterol, apoB, and apoA-I levels.  Furthermore, they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0655 -            were not obese and did not differ from normolipidemic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0656 -            subjects for abdominal fat accumulation.  It also seems                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0657 -            important to point out that men with isolated low HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0658 -            cholesterol had a VO2max at baseline as high as that of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0659 -            normolipidemic men, suggesting that they were as physically                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0660 -            fit as normolipidemic men.  These results are consistent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0661 -            with our previously published study in which we reported                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0662 -            that patients with isolated hypoalphalipoproteinemia were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0663 -            not characterized by abdominal obesity or by the features                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0664 -            of insulin resistance.12 Because these patients were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0665 -            neither overweight nor hyperinsulinemic, we hypothesized                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0666 -            that they might show a specific response pattern to a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0667 -            standardized endurance exercise training program.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PJ0669 -             ..
PJ0670 -       15.  Indeed, men with high TG/low HDL cholesterol displayed the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0671 -            expected favorable changes in the lipoprotein profile in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0672 -            response to the standardized exercise training program (eg,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0673 -            decrease in plasma TG, cholesterol, LDL cholesterol, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0674 -            apoB levels and an increase in apoA-I and HDL cholesterol).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0675 -            Furthermore, the concomitant increases in HDL2 cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0676 -            and apoA-I in men with high TG/low HDL cholesterol suggest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0677 -            simultaneous effects of exercise training on the density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0678 -            and number of HDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PJ0680 -             ..
PJ0681 -       16.  On the other hand, exercise training was unsuccessful in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0682 -            raising plasma HDL cholesterol levels in subjects with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0683 -            isolated low HDL cholesterol.  The lack of response in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0684 -            subjects with isolated low HDL cholesterol could not be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0685 -            attributed to differences in the compliance to the training                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0686 -            program or to difference in cardiorespiratory adaptations,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0687 -            inasmuch as the absolute and relative increase in VO2max                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0688 -            was similar among all study groups.  Furthermore, all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0689 -            groups displayed similar favorable changes in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PJ0690 -            PH-HL/PH-LPL ratio, which we have previously shown to be a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0691 -            significant correlate of plasma HDL cholesterol levels.28                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0693 -             ..
PJ0694 -       17.  However, Williams et al43 also reported a significant and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0695 -            positive association between baseline HDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PJ0696 -            levels and the subjects' running mileage during the trial,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0697 -            which led them to suggest that greater distances and a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PJ0698 -            more important weight loss may have accounted, at least in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0699 -            part, for the larger increase in HDL cholesterol levels in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0700 -            these individuals.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PJ0702 -  ..
PJ0703 - This is the main issue on raising HDL - longer distance and weight                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0704 - loss, which means in part diet control and hiking faster, i.e.,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0705 - causing the body to reach an energy "burn-rate" sufficient to trigger                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PJ0706 - release of reserves, commonly called "fat."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PJ0708 -  ..
PJ0709 - It would seem this requires subjecting the body to conditions from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PJ0710 - which human biology evolved that required a lot of effort to obtain                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PJ0711 - life-sustaining, scarce food supply, while moving fast enough to avoid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PJ0712 - becoming food supply for others. (see next article, ref SDS 0 E265).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PJ0713 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0714 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0715 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0716 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ0717 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PJ08 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0401 -  ..
PK0402 - Exercise Genetic Requirement Human Cardiovascular Survival                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0403 - Endurance Exercise Effects Cardiovascular Endothelial Function                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0404 - Exercise Recovery Cardiovasular Disease Endothelial Function                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0405 - Cardiovasular Disease Exercise Recovery Endothelial Function                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0406 - 
PK0408 -         ..
PK0409 -        American Heart Association                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0411 -         ..
PK0412 -        Circulation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0414 -         ..
PK0415 -   22.  Exercise in Cardiovascular Disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0416 -        Cardiovascular Effects of Exercise Training                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0417 -        Molecular Mechanisms                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0418 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0419 -              http://circ.ahajournals.org/content/122/12/1221.full#sec-34                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0421 -         ..
PK0422 -        Stephan Gielen, MD; Gerhard Schuler, MD; Volker Adams, PhD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0424 -         ..
PK0425 -        Correspondence to Volker Adams, PhD, Department of Internal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0426 -        Medicine/Cardiology, University of Leipzig, Heart Center,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0427 -        Strümpellstraße 39, 04289 Leipzig, Germany. E-mail                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0428 -        adav@medizin.uni-leipzig.de                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0429 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0430 -        1.  In the natural habitat of our ancestors, physical activity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0431 -            was not a preventive intervention but a matter of survival.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0432 -            In this hostile environment with scarce food and ubiquitous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0433 -            dangers, human genes were selected to optimize aerobic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0434 -            metabolic pathways and conserve energy for potential future                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0435 -            famines.1 Cardiac and vascular functions were continuously                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0436 -            challenged by intermittent bouts of high-intensity physical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0437 -            activity and adapted to meet the metabolic demands of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0438 -            working skeletal muscle under these conditions.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0440 -             ..
PK0441 -        2.  The statistical average of physical activity in Western                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0442 -            societies is so much below the levels normal for our                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0443 -            genetic background that sedentary lifestyle in combination                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0444 -            with excess food intake has surpassed smoking as the No. 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0445 -            preventable cause of death in the United States.2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0447 -             ..
PK0448 -        3.  Cardiac Effects of Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0450 -  ..
PK0451 - This section omitted to save time, since at the moment focus of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0452 - research is on regression (i.e., recovery from) atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0453 - plaque (lesions).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0454 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0455 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0456 -        4.  Vascular Effects of Exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PK0457 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0458 -            There are several reasons why endothelial research became                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0459 -            so significant for today's mechanistic concepts of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0460 -            exercise-mediated cardiovascular effects:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0461 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0462 -            1.  Endothelial dysfunction has been found to be a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0463 -                condition sine qua non for atherogenesis (ie, an obligatory                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0464 -                initial step in early atherosclerosis).102 Thus, prevention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0465 -                of endothelial dysfunction will necessarily prevent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0466 -                atherosclerosis development.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0468 -                 ..
PK0469 -            2.  The presence of endothelial dysfunction predicts future                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0470 -                cardiovascular events.103,104 Hence, endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0471 -                function measurements were proposed as a surrogate end                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0472 -                point in clinical research.105                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0474 -                 ..
PK0475 -            3.  Endothelial function can be assessed by a large variety                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0476 -                of methods in both animal and human studies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0477 -                Surgical/invasive methods include organ bath                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0478 -                measurements of arterial rings harvested in animals or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0479 -                during aortocoronary bypass surgery in humans and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0480 -                catheter-based assessment of acetylcholine-induced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0481 -                vasodilatation with angiography of the target vessel.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0483 -                 ..
PK0484 -                Noninvasive methods such as brachial/radial ultrasound,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0485 -                magnetic resonance imaging, and venous occlusion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0486 -                plethysmography permit serial studies comparing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0487 -                endothelial function before and after an exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0488 -                intervention.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0490 -                 ..
PK0491 -                These classic methodologies are increasingly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0492 -                supplemented by commercial semiautomatic devices using,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0493 -                for example, digital pulse amplitude tonometry to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0494 -                measure microvascular function.106                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0496 -             ..
PK0497 -        5.  Exercise and Conduit Vessel Vasomotor Function in Coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0498 -            Artery Disease                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0500 -             ..
PK0501 -        6.  The clinical effects of endurance exercise training on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0502 -            coronary endothelial function were first studied in humans                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0503 -            by Hambrecht et al117:  A 4-week endurance training program                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0504 -            was effective in attenuating the paradoxical arterial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0505 -            vasoconstriction in epicardial conduit vessels by -54% and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0506 -            increased average peak flow velocity by +78% in response to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0507 -            intracoronary acetylcholine infusion.  The improvements in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0508 -            coronary endothelial function were partially lost during a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0509 -            consecutive 5-month home-based endurance training program                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0510 -            at lower intensity, and changes were related to daily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0511 -            training durations.118                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0513 -             ..
PK0514 -        7.  In a subsequent study examining training effects on the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0515 -            peripheral conduit artery function, Gokce et al119                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0516 -            measured brachial and femoral artery endothelial function                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0517 -            in patients with coronary artery disease before and after                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0518 -            a 10-week leg exercise program. They documented                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0519 -            significant improvement in endothelium-dependent,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0520 -            flow-mediated dilation in conduit arteries of the leg but                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0521 -            not the arm and hypothesized that training effects could                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0522 -            be limited to the trained limb. This may, however, also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0523 -            depend on the distribution of endothelial dysfunction and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0524 -            the intensity of the training program because Linke et                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0525 -            al120 were able to confirm improved radial artery                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0526 -            endothelial function after pure bicycle ergometer training                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0527 -            in patients with CHF.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0528 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0530 -  ..
PK0531 - Atherosclerosis Regression EPCs Increase Exercise Signals Bone Marrow                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0532 - Regression Atherosclerosis EPCs Increase Exercise Signals Bone Marrow                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0533 - EPCs Produced Bone Marrow Increased Exercise Repair Endothelial Lining                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PK0534 - 
PK0535 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0536 -        8.  Exercise and EPCs.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0537 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0538 -            The first description of postnatal vasculogenesis and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0539 -            characterization of EPCs derived from adult bone marrow                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0540 -            changed our concept of vascular plasticity in health and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0541 -            disease.138 In addition to EPCs, mesenchymal stem cells                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0542 -            also possess the potential for vascular regeneration.139                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0543 -            Both mesenchymal stem cells and EPCs are mobilized from the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0544 -            bone marrow in response to ischemia, exercise, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0545 -            neurohormonal factors (eg, vascular endothelial growth                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0546 -            factor [VEGF], placental growth factor) and critically                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0547 -            contribute to maintaining the integrity of the endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0548 -            cell layer.  EPC number and function correlate with the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0549 -            number of cardiovascular risk factors and disease severity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0550 -            and predict cardiovascular events and death from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0551 -            cardiovascular causes.140                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0553 -             ..
PK0554 -            It is a matter of continuing debate whether                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0555 -            training-induced flow changes or ischemia induction is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0556 -            required to stimulate EPC release.  In 2 clinical studies,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0557 -            we demonstrated that an increase in circulating EPCs was                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0558 -            only achieved in response to exercise-induced ischemia,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0559 -            whereas matrigel assays indicated improved EPC function in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0560 -            nonischemic training, as well.141,142 Other authors showed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0561 -            exercise-related EPC increase also in the absence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0562 -            ischemia.143,144 Prolonged strenuous exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PK0563 -            (half-marathon, marathon, or spartathlon), however, showed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0564 -            no change or a significant increase in circulating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0565 -            progenitor cells.145,?,148                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0567 -             ..
PK0568 -            The principal mechanism of EPC mobilization from the bone                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0569 -            marrow seems to depend on the activation of eNOS in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0570 -            presence of several mobilizing factors such as VEGF149 or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0571 -            placental growth factor.150 Gene-targeting studies using                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0572 -            either MMP-2151 or MMP-9152 knockout mice demonstrated that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0573 -            the presence of MMPs is crucial in ischemia-induced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0574 -            mobilization of EPCs and hence neovascularization.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0576 -             ..
PK0577 -        9.  At the molecular/cellular level, the following scenario for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0578 -            the mobilization is proposed (Figure 5):  Under steady                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0579 -            state conditions, progenitor cells reside in a niche of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0580 -            bone marrow, bound to stroma cells via adhesion molecules                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0581 -            such as vascular cell adhesion molecule/very late                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0582 -            antigen-4.153 Signal-induced upregulation of MMP-9 results                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0583 -            in a release of sKitL, conferring signals that enhance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0584 -            mobility of progenitor cells into a vascular-enriched niche                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0585 -            favoring liberalization of the cells into the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PK0586 -            circulation.154                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0588 -             ..
PK0589 -       10.  How can we explain the exercise-induced mobilization of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0590 -            EPCs?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0592 -             ..
PK0593 -            In several studies, it was demonstrated that exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0594 -            increases the concentration of NO,132 which in turn can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0595 -            activate MMP-9 in bone marrow,155 leading to enhanced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0596 -            mobilization of progenitor cells, as depicted above.  As                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0597 -            soon as the EPCs are circulating, the most important                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0598 -            factors for tissue engraftment of the mobilized cells are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0599 -            the local concentration of stromal-derived factor-1? and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0600 -            its cell receptor CXCR4.156 This notion is further                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0601 -            supported by the observation that mice lacking CXCR4 die in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0602 -            utero because of defects in vascular development.157                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0603 -            Although the animal data make shear stress-induced NO                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0604 -            generation a likely mechanism for NO-mediated EPC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0605 -            mobilization, animal experiments with ischemic exercise are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0606 -            still lacking.  Therefore, the aforementioned controversy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0607 -            still awaits experimental resolution.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0608 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0610 -  ..
PK0611 - Exercise Causes Atherosclerosis Regression for Endurance Training                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0612 - 
PK0613 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0614 -       11.  Exercise and Plaque Regression in CAD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0615 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0616 -            Although it is high on the agenda in lipid research, plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0617 -            regression ceased to be a research focus of exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0618 -            research in recent years.  Two decades ago, a series of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0619 -            angiographic long-term follow-up studies documented that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0620 -            regular endurance exercise training can retard the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0621 -            progression of coronary atherosclerosis158,159 or even                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0622 -            reduce stenosis diameter if combined with lipid-management                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0623 -            techniques of smoking cessation and other lifestyle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0624 -            interventions.160,161 Surprisingly, not a single study has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0625 -            addressed exercise-mediated changes in plaque volume by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0626 -            intravascular ultrasound thus far to control the findings                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0627 -            of the early regression studies with a more accurate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0628 -            technique, which also permits insight into changes of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0629 -            plaque composition.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0631 -  ..
PK0632 - Atherosclerotic plaque regression through regular endurance exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0633 - training may have ceased to be a focus of research studies noted in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0634 - this article, ref SDS 0 XY7L, because getting enough subjects with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0635 - time and capacity may be difficult.  Generally, patients retired or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0636 - unable to work due to medical impairments have time available every                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0637 - day, but often lack capacity to perform daily endurance exercise at a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0638 - level sufficient to trigger increase in HDL and EPCs.  Patients with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0639 - capacity for endurance exercise training at a level sufficient to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0640 - increase HDL and EPCs lack the time to perform daily endurance                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0641 - training because of obligations to work and family life.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PK0642 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0643 -               [...above on 131125 0005 another article presents theory                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0644 -               and practice finding elevated HDL and EPCs cause rapid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0645 -               regression of atherosclerotic plaques. ref SDS 0 6S7F                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0646 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0648 -  ..
PK0649 - Article Exercise in Cardiovascular Disease continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0650 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0651 -       12.  Conclusion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0652 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0653 -            To summarize, cardiac effects of exercise include an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0654 -            improved protection against I/R injury primarily as a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0655 -            result of higher antioxidative protection and improved LV                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0656 -            diastolic and systolic function in chronic heart failure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0657 -            due to favorable changes in neurohormonal state,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0658 -            activation of PI3K (p110?) attenuating pathological                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0659 -            hypertrophy, normalization of cardiomyocyte calcium                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0660 -            handling, and inhibition of the catabolic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0661 -            ubiquitin-proteasome system.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PK0663 -             ..
PK0664 -       13.  Vascular effects are based on improved endothelium-mediated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0665 -            flow-induced vasodilatation in conduit arteries and larger                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0666 -            resistance arteries, higher myogenic control, and increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0667 -            metabolic vasodilatation in small resistance arteries.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0668 -            Vascular regeneration by mobilization of endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0669 -            progenitor cells is augmented by exercise.  Recently,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0670 -            improved endothelial vasodilatation has also been confirmed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0671 -            in the pulmonary artery.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0672 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0673 -               [On 140515 2043 letter to VA requests adding EPC to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0674 -               supplemental lab for Electrolyte Panel (Chem Profile),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0675 -               and for the purpose of evaluating prospects for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PK0676 -               regression of atherosclerotic plaques. ref SDS 61 YM61                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0678 -                ..
PK0679 -               [On 140520 0732 letter to VA notifies Doctor Alba about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0680 -               adding EPC to follow up lab ordered to test Electrolyte                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0681 -               panel (Chem Profile). ref SDS 64 4U46                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0683 -                ..
PK0684 -               [On 140520 0732 at 1028 letter from Doctor Alba requests                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0685 -               clarification for adding EPC to lab order. ref SDS 64                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0686 -               654J Called to explain scope of EPC lab, but encountered                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0687 -               poor connection using cell phone. ref SDS 64 U63N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0689 -                ..
PK0690 -               [On 140626 1652 letter notifies VA of case studies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0691 -               showing failure to perform timely testing causes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0692 -               negative patient outcomes. ref SDS 65 MY51  VA reference                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0693 -               to patient having vessel plaques 5 years ago, begs the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0694 -               question of testing to determine currently how much                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0695 -               plaque, and level of care required, if any, to treat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0696 -               current condition. ref SDS 65 MZ33  Evidence shows CTA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0697 -               common procedure to evaluate current condition post CABG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0698 -               surgery. ref SDS 65 MZ54                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PK0700 -                ..
PK0701 -               [On 140703 1938 Doctor Alba reports EPC issue discussed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PK0702 -               among team at VA in detail; determined no justification                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0703 -               to evaluate EPC toward coronary CTA to assess regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PK0704 -               of atherosclerosis, ref SDS 66 H167, which VA maintains                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0705 -               requires treatment, shown in Progress Notes on 140519                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0706 -               0800, ref SDS 63 OW76, based solely on history of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0707 -               atherosclerosis requiring CABG x4 surgery on 091022, 5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0708 -               years ago, as presented in VA Progress Notes on 140519                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0709 -               0800, ref SDS 63 OW49, and without knowledge of actual                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PK0710 -               current condition resulting from intervening events,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0711 -               e.g., 120% rise from HDL 30 to HDL 67, shown in labs on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0712 -               140514 0950. ref SDS 58 W25L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0714 -             ..
PK0715 -       14.  Extending our concept of molecular mechanisms of exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0716 -            is essential to further optimize training interventions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PK0717 -            with regard to their clinical efficacy and to identify                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PK0718 -            novel targets for pharmaceutical intervention.  However,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PK0719 -            certain areas (ie, microcirculation and the venous system)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PK0720 -            are still incompletely understood and merit further                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PK0721 -            molecular studies. Residual incomplete molecular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0722 -            understanding should not prevent the clinical use of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0723 -            training interventions with established clinical benefit.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0725 -  ..
PK0726 - This article notes conceptual correlation between endurance exercise                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PK0727 - at system signal levels and production of EPS, required for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0728 - endothelial layer repair of circulatory system that removes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PK0729 - atherosclerosis plaques, cited in articles above. ref SDS 0 Z49G                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PK0730 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0731 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0732 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK0733 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PK08 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0401 -  ..
PL0402 - Endothelial Cells Regression Atherosclerosis Integrated HDL Effects                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0403 - HDL EPC Elevated Causes Rapid Regression Atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0404 - EPC HDL Elevated Causes Rapid Regression Atherosclerosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0405 - Atherosclerosis Elevated HDL EPC Causes Rapid Regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0406 - 
PL0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0408 - Another article says...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL0409 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0410 -        Experimental & Clinical Cardiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0412 -         ..
PL0413 -        An integrated approach for the mechanisms responsible for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0414 -        atherosclerotic plaque regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0415 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0416 -        by Andrew A Francis, BSc and Grant N Pierce, PhD FACC FAHA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0417 -        FISHR FIACS FCAHS FRSM FAPS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0419 -         ..
PL0420 -        Exp Clin Cardiol. 2011 Fall; 16(3): 77?86.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0422 -         ..
PL0423 -        PMCID: PMC3209544                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PL0425 -         ..
PL0426 -        Review                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0428 -         ..
PL0429 -        Institute of Cardiovascular Sciences, St Boniface Hospital                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0430 -        Research Centre, Department of Physiology, Faculties of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0431 -        Medicine and Pharmacy, University of Manitoba, Winnipeg,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0432 -        Manitoba                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0434 -         ..
PL0435 -        Correspondence: Dr Grant N Pierce, Institute of Cardiovascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0436 -        Sciences, St Boniface Hospital Research Centre, 351 Tache                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0437 -        Avenue, Winnipeg, Manitoba R2H 2A6. Telephone 204-235-3206,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0438 -        fax 204-235-0793, e-mail gpierce/at/sbrc.ca                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0440 -         ..
PL0441 -        Received July 25, 2011; Accepted July 27, 2011.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0442 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0443 -        1.  Abstract                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0444 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0445 -            Atherosclerosis was originally considered to be an ongoing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0446 -            process that was inevitably associated with age.  However,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0447 -            plaques are highly dynamic, and are able to progress,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0448 -            stabilize or regress depending on their surrounding milieu.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0449 -            A great deal of research attention has been focused on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0450 -            understanding the involvement of high-density lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0451 -            in atherosclerotic plaque regression.  However,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0452 -            atherosclerotic plaque regression encompasses a variety of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0453 -            processes that can be grouped into three main areas:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0454 -            removal of lipids and necrotic material; restoration of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0455 -            endothelial function and repair of denuded areas; and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0456 -            cessation of vascular smooth muscle cell proliferation and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0457 -            phenotype reversal.  In addition to the role of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0458 -            high-density lipoproteins in lipid removal, resident                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0459 -            macrophages and foam cells are able to regain motility and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0460 -            rapidly migrate on milieu improvement, moving both lipids                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0461 -            and necrotic material to regional lymph nodes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0462 -            Neighbouring endothelial cells can proliferate and replace                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0463 -            dead and dysfunctional cells.  Circulating endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0464 -            progenitor cells can similarly restore vessel function.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0465 -            Finally, abrogation of smooth muscle cell proliferation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0466 -            occurs secondarily to these processes.  This information is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0467 -            integrated in the current article to present a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0468 -            comprehensive and clear depiction of plaque regression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0469 -            This integrated view of regression is essential to optimize                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0470 -            the pharmaceutical targeting of the many processes and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0471 -            pathways involved in plaque regression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0472 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0473 -               [On 140626 1652 letter notifies VA of case studies                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0474 -               showing failure to perform timely testing causes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0475 -               negative patient outcomes. ref SDS 65 MY51  VA reference                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0476 -               to patient having vessel plaques 5 years ago, begs the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0477 -               question of testing to determine currently how much                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0478 -               plaque, and level of care required, if any, to treat                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0479 -               current condition. ref SDS 65 MZ33  Evidence shows CTA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0480 -               common procedure to evaluate current condition post CABG                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0481 -               surgery. ref SDS 65 MZ54                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0483 -                ..
PL0484 -               [On 140703 1938 Doctor Alba reports EPC issue discussed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0485 -               among team at VA in detail; determined no justification                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0486 -               to evaluate EPC toward coronary CTA to assess regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0487 -               of atherosclerosis, ref SDS 66 H167, which VA maintains                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0488 -               requires treatment, shown in Progress Notes on 140519                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0489 -               0800, ref SDS 63 OW76, based solely on history of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0490 -               atherosclerosis requiring CABG x4 surgery on 091022, 5                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0491 -               years ago, as presented in VA Progress Notes on 140519                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0492 -               0800, ref SDS 63 OW49, and without knowledge of actual                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0493 -               current condition resulting from intervening events,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0494 -               e.g., 120% rise from HDL 30 to HDL 67, shown in labs on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0495 -               140514 0950. ref SDS 58 W25L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0497 -             ..
PL0498 -        2.  Atherosclerosis emerged as a major health dilemma during                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0499 -            the early 20th century. Nearly a full century later,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0500 -            atherosclerosis has become the leading cause of death                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0501 -            worldwide (1,2). It is now understood that atherosclerotic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0502 -            lesions are produced from a complex array of molecular and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0503 -            cellular events that act in concert to form asymmetric                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0504 -            focal thickenings of the arterial tunica intima (3,4).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0506 -             ..
PL0507 -        3.  Atherosclerosis is initiated by the response of endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0508 -            cells (ECs) to injury caused by myriad noxious stimuli                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0509 -            including hyperglycemia, hypertension, hyperlipidemia,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0510 -            infectious agents, obesity, modified lipoproteins,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0511 -            homocysteine, nicotine, free radicals, altered changes in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0512 -            arterial blood flow shear stress and normal spontaneous                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0513 -            metabolic damage (5?10).  This initial damage induces a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0514 -            loss of basal endothelial homeostasis causing endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0515 -            dysfunction (11).  The resulting increase in endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0516 -            permeability permits the accumulation of low-density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0517 -            lipoprotein (LDL) and cellular debris within the tunica                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0518 -            intima of the vessel wall, eventually leading to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0519 -            endothelial activation.  Once activated, ECs produce an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0520 -            array of chemoattractant cytokines such as monocyte                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0521 -            chemoattractant protein-1, macrophage colony-stimulating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0522 -            factor, interferon-?, platelet-endothelial cell adhesion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0523 -            molecule-1, interleukin (IL)-1, IL-6 and tumour necrosis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0524 -            factor-? (TNF-?), creating a proinflammatory environment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0525 -            that attracts circulating monocytes and T lymphocytes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0526 -            (12?14).  Normally, ECs do not express molecules that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0527 -            facilitate the adhesion of circulating leukocytes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0528 -            However, activated ECs express vascular cell adhesion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0529 -            molecules such as intercellular adhesion molecules (ICAMs),                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0530 -            E-selectin and P-selectin, which mediate leukocyte adhesion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0531 -            and infiltration (12,13).  Endothelial-derived cytokines                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0532 -            subsequently drive the differentiation of monocytes into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0533 -            macrophages, which use pattern recognition receptors to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0534 -            sequester LDL, modified LDL, free cholesterol (FC) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0535 -            cholesteryl esters (3).  Together, activated leukocytes and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0536 -            ECs continue to produce proinflammatory cytokines and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0537 -            growth factors that promote the transition of smooth muscle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0538 -            cells from a quiescent, contractile phenotype to an active                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0539 -            and proliferative synthetic phenotype that deposits                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0540 -            extracellular matrix at the site of injury, forming a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0541 -            fibrous cap (15?18).  Continued exposure to various                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0542 -            noxious stimuli, in conjunction with a proinflammatory                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0543 -            environment, further exacerbates plaque severity,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0544 -            perpetuates plaque progression, and promotes plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0545 -            destabilization, resulting in plaque rupture which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0546 -            manifest as acute events such as stroke or myocardial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0547 -            infarction (19,20).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0549 -             ..
PL0550 -        4.  During the past few decades, an improved understanding of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0551 -            atherosclerotic pathophysiology has enabled researchers to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0552 -            consider the possibility of inducing plaque regression in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0553 -            addition to the more conventional therapeutic goal of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0554 -            reducing plaque progression.  Traditionally,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL0555 -            atherosclerosis was viewed as an inevitable unidirectional                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0556 -            process that begins in childhood and manifests during                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0557 -            adulthood (20).  However, during the 1980s, Badimon et al                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0558 -            (21) showed that plaque development is not simply a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0559 -            permanent process associated with age, but rather a dynamic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0560 -            process that can be slowed, stopped or reversed.  In spite                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0561 -            of the evidence supporting the existence of plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0562 -            regression, the concept of "plaque regression" was resisted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0563 -            for decades.  Critics of regression asserted that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0564 -            physical attributes of an atherosclerotic plaque, including                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0565 -            calcification, necrosis and fibrosis, indicated stability,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0566 -            and the molecular processes associated with plaques such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0567 -            oxidative damage, cell proliferation and transformation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0568 -            seemed to imply that regression would be very difficult or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0569 -            impossible to achieve.  Furthermore, at that time, a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0570 -            majority of animal studies attempting to induce regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0571 -            in advanced plaques had failed (22?26).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0573 -             ..
PL0574 -        5.  However, the ability of even advanced lesions to regress on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0575 -            robust reductions in LDL levels and increases in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0576 -            high-density lipoprotein (HDLs) levels has established                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0577 -            plaque regression as a well-accepted process (27,28).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0578 -            Atherosclerosis is now known as a highly dynamic process in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0579 -            which plaques are able to either progress or regress,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0580 -            depending on the surrounding milieu (29,30).  However,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0581 -            despite the plethora of research, a comprehensive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0582 -            discussion that incorporates and integrates the current                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0583 -            knowledge of the various processes known to occur during                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0584 -            plaque regression remains to be completed.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0586 -  ..
PL0587 - Atherosclerosis plaque regression is now a "well established process"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0588 - on "robust" reduction of LDL - does this correlate with LDL-P < 1000
PL0589 - or LDL-C < 70 - at this time the matter is not addressed in the
PL0590 - research??  Or, does "robust reduction of LDL" simply correlate to HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0591 - reaching sufficiently elevated level (i.e., >= 60) for "reverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0592 - cholesterol transport" (RTC) to occur, discussed in this artical 2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0593 - paragraphs below? ref SDS 0 HG7N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0595 -  ..
PL0596 - Correlating regression of atherosclerosis plaque solely on robust                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0597 - reduction of LDL and increase of HDL further seems to ignore the role                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0598 - of increasing EPCs, cited initially and extensively in the same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0599 - article below. ref SDS 0 FV5L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0601 -  ..
PL0602 - Article continues...                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PL0603 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0604 -        6.  What is atherosclerotic plaque regression?  Ideally, plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0605 -            regression would be the return of the arterial wall to its                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0606 -            initial state.  However, with the exception of fatty                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0607 -            streaks, even under ideal conditions, the complete reversal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0608 -            of plaque formation does not occur (30).  It is important                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0609 -            to understand that plaque regression is not simply plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0610 -            progression in reverse.  Rather, the mechanisms of plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0611 -            regression are distinct and are composed of three important                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0612 -            processes: the reduction or clearance of necrotic and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0613 -            extracellular material from the tunica intima; endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0614 -            repair, regeneration and return to homeostasis; and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0615 -            cessation of smooth muscle cell proliferation (Figure 1).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0616 -            Although a reduction of luminal area, plaque volume or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0617 -            intimal medial thickness are indexes commonly used in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0618 -            diagnostic medicine to assess plaque regression, and are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0619 -            possible estimations of regression, they are currently                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0620 -            unable to capture the true complexity of this process.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0622 -             ..
PL0623 -        7.  REMOVAL OF EXTRACELLULAR AND INTRACELLULAR LIPIDS AND                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0624 -            NECROTIC MATERIAL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0626 -             ..
PL0627 -            Although the mechanisms of regression are beginning to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0628 -            understood, there has been considerable progress in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0629 -            isolating the important players in regression and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0630 -            understanding their biological role. Attention, however,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0631 -            within the past few decades has been focused on reverse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0632 -            cholesterol transport (RCT) and its major player, HDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0634 -             ..
PL0635 -        8.  HDL and its influence on atherosclerotic plaque regression though RCT                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0636 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0637 -            HDL classification:  Since the early 1970s, HDL cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0638 -            (HDL-C) has been associated with a decrease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0639 -            cardiovascular disease (CVD) (31).  Gordon et al (32)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0640 -            demonstrated that there is an inverse relationship between                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0641 -            systemic levels of HDL-C and the prospective risk for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0642 -            coronary artery disease; this correlation was maintained                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0643 -            even at very low levels of LDL cholesterol.  Animal and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0644 -            human studies have shown that infusions of synthetic HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0645 -            particles can induce regression of atherosclerotic plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0646 -            (21,33,34).  Moreover, increases in HDL-C by even 1 mg/dL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0647 -            are associated with a 3% to 4% decrease in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0648 -            cardiovascular-related mortality (35).  Since the discovery                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0649 -            of the inverse relationship of HDL-C with CVD, a large                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0650 -            amount of information has been obtained about its structure                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0651 -            and function.  Although the full mechanism of HDL?s                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0652 -            anti-atherosclerotic effects are not well known, it is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0653 -            becoming clear that HDL participates in ameliorating nearly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0654 -            all aspects of plaque pathogenicity by restoring                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0655 -            endothelial cell basal function, decreasing smooth muscle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0656 -            cell proliferation and migration, and decreasing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0657 -            intraplaque inflammation and cellular debris retention                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0658 -            (36).  It has also become clear that not only is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0659 -            concentration of HDL within the circulation important for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0660 -            its anti-inflammatory effect, but also its quality (37).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0661 -            Nevertheless, what has been well established is HDL?s                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0662 -            contribution to atherosclerotic plaque regression by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0663 -            promoting RCT.  However, to understand the RCT pathway, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0664 -            is essential to become aware of the various structures of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0665 -            HDL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0667 -             ..
PL0668 -        9.  HDLs were first discovered by Gofman et al (38) in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0669 -            experimental studies using analytical ultracentrifugation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0670 -            to separate and categorize distinct serum lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0671 -            families according to their hydrated density.  HDLs were                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0672 -            defined as lipoproteins of small diameter (5 nm to 17 nm)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0673 -            that sediment in the density region (1.063 g/mL to 1.21                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0674 -            g/mL) (Table 1).  It is now understood that HDL is a highly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0675 -            heterogeneous group of particles, and composed of many                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0676 -            subclasses.  The difference between HDL subclasses is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0677 -            ultimately dependent on the particles' physical properties                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0678 -            including shape, size, density and charge; however, these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0679 -            subclasses can be reclassified according to differences in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0680 -            lipid transfer proteins, enzymes, lipid content and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0681 -            apolipoproteins (39,40).  Many methods have been developed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0682 -            to separate HDL into its various subclasses.  Gofman et al                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0683 -            (38) developed an analytical ultracentrifugation method for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0684 -            identifying the distinct subclasses of HDL particles, which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0685 -            is currently the gold standard technique for HDL subclass                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0686 -            determination (41,42).  Using this technique and other                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0687 -            ultracentrifugation methods, such as rate-zonal or single                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0688 -            vertical spin ultracentrifugation, HDLs can be separated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0689 -            into two main subfractions based on their respective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0690 -            densities:  HDL2 (1.063 g/mL to 1.125 g/mL) and HDL3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0691 -            (>1.125 g/mL to 1.21 g/mL) (43?45).  These two HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0692 -            subfractions can also be further subdivided based on their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0693 -            size (diameter) using nondenaturing polyacrylamide gel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0694 -            electrophoresis, yielding HDL2b (9.7 nm to 12.0 nm), HDL2a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0695 -            (8.8 nm to 9.7 nm), HDL3a (8.2 nm to 8.8 nm), HDL3b (7.8 nm                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0696 -            to 8.2 nm) and HDL3c (7.2 nm to 7.8 nm) (46).  Another                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0697 -            classification system of HDL arose with the use of agarose                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0698 -            gel electrophoresis, separating HDL based on relative                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0699 -            negative surface charge density. ?-HDL, which comprises the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0700 -            majority of plasma HDL, has a high negative charge density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0701 -            compared with pre?-HDL, also known as nascent HDL (47?49).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0702 -            Two-dimensional electrophoresis, which combines both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0703 -            agarose gel and gradient gel electrophoresis, can further                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0704 -            resolve -HDL and pre-HDL into 12 distinct HDL subclasses                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0705 -            based on their size and motilities with respect to albumin:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0706 -            pre- (pre-1, pre-2 and pre-3), - (-1, -2 and ?-) and pre-                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0707 -            (pre-1, pre-2 and pre-3) (48,50).  Finally, HDL can be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0708 -            classified by immunoaffinity methods according to its                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0709 -            apolipoprotein (apo) A composition.  The majority of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0710 -            proteins found in HDL are either apoAI (65% to 70%) and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0711 -            apoAII (20% to 25%).  Furthermore, two major                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL0712 -            apoA-containing HDL subclasses exist:  HDL particles may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0713 -            contain both apoAI and apoAII in a 2:1 molar ratio, or they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0714 -            can contain only apoAI (50,51).  Adding to HDL?s                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0715 -            complexity, several proteins have been shown to circulate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0716 -            in the plasma bound to HDL including apoA-IV, apoC, apoE,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0717 -            apoF, lecithin:cholesterol acyltransferase, cholesteryl                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0718 -            ester transferase (CETP), phospholipid transferase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0719 -            protein, paraoxonase and platelet-activating factor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0720 -            acetylhydrolase. Moreover, proteomic analyses have shown                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0721 -            that HDL may contain more than 48 proteins. It is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0722 -            generally accepted that the majority of plasma HDL is in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0723 -            the form of pre?-HDL, as well as HDL2 and HDL3 ? the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0724 -            mature forms of HDL that are equivalent to ?-HDL (52,53)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0725 -            (Table 1). Despite the many different classifications of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0726 -            HDL, all HDL particles have in common their ability to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0727 -            mediate the process of RCT.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0729 -             ..
PL0730 -       10.  RCT: According to the generally accepted definition of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0731 -            RCT, the first step of RCT is the efflux of extrahepatic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0732 -            cholesterol from intracellular cholesterol pools. This                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0733 -            usually focuses on the removal of cholesterol from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0734 -            macrophages. Alternatively, critics of this view attest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0735 -            that assembly of HDL particles and their subsequent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0736 -            secretion into the circulation is the initial step of this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0737 -            process (54?56). In the present review, however, the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0738 -            overview of HDL?s involvement in RCT will begin with the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0739 -            production and release of HDL to provide a clear synopsis                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0740 -            of RCT. Despite the disagreement regarding the initial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0741 -            steps in RCT, it is accepted that the acquisition of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0742 -            cholesterol from peripheral stores by HDL is the major                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0743 -            mechanism for promoting atherosclerotic plaque regression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0745 -             ..
PL0746 -       11.  The production of all HDL subclasses begins with the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0747 -            synthesis of apoAI and apoAII.  These proteins are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0748 -            primarily generated in the liver and secondarily by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0749 -            small intestine (56,57).  Both hepatocytes and enterocytes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0750 -            can secrete lipid-poor apoAI and AII into the circulation,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0751 -            where it acquires phospholipids and cholesterol to form                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0752 -            pre?-HDL (58?60).  Regardless, the majority of apoA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0753 -            produced in the intestine is packaged into chylomicrons,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0754 -            which are eventually internalized by the liver.  In                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0755 -            contrast, hepatocyte apoA secretion into plasma is more                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0756 -            complex.  Similar to chylomicrons, very low density                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0757 -            lipoprotein (VLDL) ? another triglyceride-rich lipoprotein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0758 -            ? can lose cholesterol.  Phospholipids can also lose or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0759 -            gain apolipoproteins during lipolysis, which generates                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0760 -            pre?-HDL. VLDL can also be amalgamated into HDL2 and HDL3                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0761 -            (61). Finally, hepatocytes can synthesize and secrete both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0762 -            apoA and pre?-HDL directly into the circulation. In spite                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0763 -            of the different modes of release, once in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0764 -            circulation, pre?-HDL can be used for RCT.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0766 -             ..
PL0767 -       12.  The first and rate-limiting steps of RCT is cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0768 -            efflux from macrophages, and the peripheral tissue to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0769 -            HDL particle (62).  There are currently four proposed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0770 -            mechanisms of cholesterol efflux into lipid-poor apoAI and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0771 -            the various HDL particles: aqueous diffusion, scavenger                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0772 -            receptor class B type 1 (SR-BI)-mediated efflux,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0773 -            ATP-binding cassette (ABC) transporter A1-mediated efflux                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0774 -            and ABCG1-mediated efflux (54,55).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0776 -             ..
PL0777 -       13.  First, cholesterol efflux can occur passively by adhering                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0778 -            to its concentration gradient.  As a result, the passive                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0779 -            diffusion pathway is bidirectional, and the rate-limiting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0780 -            step of this process is dependent on the ratios and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0781 -            interactions between the FC in the donor cells and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0782 -            phospholipids within the plasma membrane of the acceptor                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0783 -            molecule ? the HDL particle (62,63).  The kinetics of this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0784 -            interaction are accelerated by higher proportions of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0785 -            unsaturated phospholipids and decreases in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0786 -            sphingomyelin content of the plasma membrane (64,65).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0787 -            Because cholesterol efflux by this pathway is not affected                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0788 -            by HDL particle size, all HDL subclasses are equal in their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0789 -            ability to accept cholesterol through aqueous diffusion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0790 -            (66).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0792 -             ..
PL0793 -       14.  In contrast to aqueous diffusion, the remaining three                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0794 -            cholesterol efflux pathways are mediated by protein-protein                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0795 -            interactions.  Cholesterol efflux can be mediated by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0796 -            ATP-independent, passive SR-BI pathway.  Cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0797 -            transport is initiated by the binding of HDL to SR-BI,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0798 -            which subsequently forms a hydrophobic channel allowing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0799 -            efflux to occur (67).  SR-BI promotes efflux exclusively to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0800 -            larger, more mature HDL particles such as HDL2 and HDL3,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0801 -            which can further increase the SR-BI-mediated selective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0802 -            uptake of cholesterol if they contain apoAII (68).  Because                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0803 -            this process is bidirectional, HDL may be a donor and an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0804 -            acceptor of cholesterol.  Thus, its role in aiding RCT in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0805 -            macrophages may not be as important as the remaining                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0806 -            energy-dependent cholesterol efflux pathways (69).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0808 -             ..
PL0809 -       15.  Cholesterol and phospholipid efflux to apoAI is promoted                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0810 -            by the interaction of ABCA1 with pre?-HDL or with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0811 -            lipid-poor apoAI (49). The activation of ABCA1 induces the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0812 -            removal of cholesterol from the plasma membrane of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0813 -            donor cell and can also cause efflux from intracellular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0814 -            cholesterol pools (70,71). The rate of lipid efflux is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0815 -            dependent on the concentration of activated ABCA1 and on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0816 -            the amount of unsaturated phospholipids in the donor cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0817 -            (72). In addition, the concentration of ABCA1 in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0818 -            plasma membrane is regulated by the interaction of apoA1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0819 -            and ABCA1, which prevents its intracellular degradation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0820 -            (73).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0822 -             ..
PL0823 -       16.  Another member of the ABC family of transporters, ABCG1,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0824 -            is the last major efflux pathway in RCT. ABCG1, which is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0825 -            involved with regulating intracellular cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0826 -            homeostasis, interacts with all subclasses of HDL (74?76).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0827 -            It also mediates cholesterol efflux through the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0828 -            reorganization of existing cholesterol pools, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0829 -            increasing its diffusion to and uptake by HDL particles.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0830 -            Although all HDL subclasses can mediate efflux through the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0831 -            ABCG1 pathway, larger HDL particles are more effective                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0832 -            acceptors, as in the SR-BI efflux pathway (77).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0834 -             ..
PL0835 -       17.  Following the removal of cholesterol from peripheral sites,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0836 -            HDL undergoes further maturation characterized by increased                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0837 -            particle size due to the progressive accumulation of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0838 -            cholesterol (78).  In circulation, cholesterol becomes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0839 -            esterified to pre-HDL through an apoA1-mediated reaction                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0840 -            with lecithin:cholesterol acyltransferase, converting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0841 -            lecithin and cholesterol into lysolecithin and CE (79).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0842 -            Because CE are hydrophobic, they can move to the developing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0843 -            core of the HDL particle, which causes it to enlarge and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0844 -            become spherical.  This ultimately transforms pre-HDL into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0845 -            HDL3 or HDL2.  This process not only increases the surface                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0846 -            area for FC acceptance, it also helps maintain the FC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0847 -            gradient (69,80).  Once a mature HDL particle is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0848 -            synthesized, it has three possible fates.  First, lipolytic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0849 -            enzymes such as lipoprotein, hepatic and endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0850 -            lipases can hydrolyze triglycerides and phospholipids                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0851 -            causing apoAI to dissociate from HDL, which facilitates the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0852 -            clearing of apoAI from circulation by the kidneys and the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0853 -            conversion of mature HDL particles back into nascent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0854 -            pre-HDL (81?83).  Second, constituents of mature HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0855 -            particles may be transported to other HDL subclasses or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0856 -            other lipoproteins.  For example, certain plasma lipid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0857 -            transfer proteins can transfer triacylglycerol and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0858 -            phospholipids among lipoproteins (84).  CETP transfers the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0859 -            majority of CEs to apoB-containing lipoproteins, such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0860 -            VLDL and LDL, which produces small cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0861 -            ester-depleted HDL particles that are either cleared by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0862 -            kidneys or incorporated into another HDL particle forming a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0863 -            large mature HDL particle (85).  ApoB-containing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0864 -            lipoproteins can be removed from the circulation by hepatic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0865 -            LDL receptors and catabolized by the liver, and hepatic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0866 -            SR-BI can also bind LDL and VLDL.  Thus, the CETP pathway                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0867 -            is believed to be an important route of RCT (86?90).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0868 -            However, clinical studies involving humans with CETP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0869 -            deficiencies report conflicting and controversial results,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0870 -            which ultimately has led to questioning of whether CETP is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0871 -            detrimental or instrumental in CVD (19,91?94).  It is also                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0872 -            likely that cholesterol transferred to LDL or VLDL can be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0873 -            redeposited to peripheral tissue.  Third, cholesterol can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0874 -            be returned to the liver through the clearance of HDL from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0875 -            the circulation.  SR-BI, located on the surface of liver or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0876 -            adrenal cells, recognizes circulating HDL particles and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0877 -            facilitates the unloading of their FC and cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0878 -            esters (95).  This process does not involve the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0879 -            internalization and degradation of the HDL particle.  Thus,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0880 -            removal of cholesterol and CEs produces nascent HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0881 -            particles that have the potential to be recycled back into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0882 -            the RCT pathway (85).  As opposed to HDL efflux from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0883 -            macrophages, SB-RI is the most abundant receptor on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0884 -            hepatocytes, thus making this pathway an important mode of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0885 -            cholesterol influx.  An alternative method of influx                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0886 -            involves the acquisition of apoE enabling HDL to deliver                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0887 -            cholesterol to hepatic tissue through its interaction with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0888 -            LDL receptors, which mediates the internalization of HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0889 -            particles and their subsequent catabolism (96).  Novel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0890 -            routes to HDL holoparticle uptake by hepatocytes, such as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0891 -            HDL internalization by the receptor P2Y13, continue to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0892 -            identified (97).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0894 -             ..
PL0895 -       18.  Cholesterol within hepatocytes must be secreted into the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0896 -            intestinal lumen to complete the RCT pathway. The rate of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0897 -            cholesterol excretion is dependent on several transporters                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0898 -            on its apical membrane. Cholesterol efflux into bile is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0899 -            dependent on both SR-BI and the ABC family of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PL0900 -            transporters. The rate of cholesterol efflux is primarily                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0901 -            controlled by ABCG5 and ABCG8 transporters (98,99).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0902 -            Although SR-BI can also facilitate cholesterol secretion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0903 -            into bile, it serves only a minor role on the apical                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0904 -            membrane, being secondary to the ABC transporters.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0905 -            However, SR-BI is an important mode of influx on the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0906 -            basolateral membrane of hepatocytes (100,101).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0908 -             ..
PL0909 -       19.  The hepatobiliary route of HDL-C removal is generally                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0910 -            accepted to be the major mode of cholesterol excretion.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0911 -            However, Cheng and Stanley (102) suggested that there is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0912 -            an additional route to fecal cholesterol loss through a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0913 -            nonbiliary fecal route. Nonbiliary sterol loss is believed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0914 -            to be regulated by the liver. Under conditions in which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0915 -            the hepatic cholesterol load exceeds a manageable amount,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0916 -            cholesterol is repackaged into plasma lipoproteins that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0917 -            are bound for secretion by the intestines (103). Although                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0918 -            the mechanism of the nonbiliary fecal pathway is not well                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0919 -            understood, many aspects are shared with the hepatobiliary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0920 -            route of sterol loss. It has been suggested that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0921 -            lipoproteins responsible for the transport of cholesterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0922 -            to the intestine are either apoE-rich HDL or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL0923 -            apoB-containing lipoproteins (104,105). It is quite likely                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0924 -            that most lipoproteins are able to facilitate this process                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0925 -            because enterocytes express SB-RI on their basolateral                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0926 -            membrane (78). Similar to hepatocytes, enterocytes express                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0927 -            ABCG5/G8 as well as SR-BI on their apical membranes,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0928 -            allowing the efflux of cholesterol from the enterocyte to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0929 -            the intestinal lumen (106).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL0931 -             ..
PL0932 -       20.  Monocyte/macrophage migration                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PL0933 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0934 -            During regression, cholesterol removal is accompanied by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0935 -            the disappearance of macrophage and foam cells. This is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0936 -            one of the first noticeable indications of plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0937 -            regression (30). It was initially believed that the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0938 -            disappearance of monocytes and macrophages from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0939 -            atherosclerotic plaques was only caused by apoptosis,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0940 -            lysis in situ and phagocytosis by new macrophages.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0941 -            However, it is now evident that macrophages within                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0942 -            atherosclerotic lesions can also regain motility and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0943 -            migrate to regional lymph nodes when the local environment                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0944 -            improves.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0946 -             ..
PL0947 -       21.  Mechanisms of cell motility and immobilization: Cells                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0948 -            facilitate migration through cell motility cycling. This                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0949 -            process contains four sequential events beginning with the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0950 -            following: polarization of the cell; extension of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0951 -            lamellipodia at the leading edge; the formation of a focal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0952 -            adhesion attaching the cell to the underlying substrate;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0953 -            and the contraction and rear detachment of the cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0954 -            resulting in cell movement. The regulation of these events                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0955 -            is coordinated by the Rho family of GTPase (107). The                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0956 -            exchange of GDP for GTP activates Rho-GTPases, which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL0957 -            control cytoskeleton remodelling by activating downstream                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0958 -            targets (108). Two members of this family, RhoA ? a GTPase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0959 -            associated with actin filament organization and promotion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0960 -            of focal adhesions ? and Rac1 ? which induces                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PL0961 -            polymerization of actin that forms both lamellipodia and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0962 -            membrane ruffles ? have important roles in cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL0963 -            immobilization (109,110).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0965 -             ..
PL0966 -       22.  During atherosclerosis, macrophages within atherosclerotic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0967 -            plaques accumulate FC and CEs (111?113). Accumulation of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0968 -            cholesterol causes apoptosis and secondary necrosis in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0969 -            macrophages and impairs chemotaxis. This immobilization is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0970 -            associated with increased levels of Rac-GTP, the active                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0971 -            form of Rac, and reduced levels of RhoA. The translocation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0972 -            of Rac to the plasma membrane facilitates its activation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0973 -            Cholesterol-rich domains within the inner leaflet of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL0974 -            plasma membrane maintain Rac-GTP in the membrane. The loss                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0975 -            of proper cell polarization, cell spreading and plasma                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0976 -            membrane ruffling caused by increased Rac activity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0977 -            abrogates forward movement of the cell (114?116).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL0979 -             ..
PL0980 -       23.  Mechanisms of macrophage migration during plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0981 -            regression: The migration of macrophage and foam cells                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0982 -            from atherosclerotic plaques is complex and is controlled                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0983 -            by plaque dynamics. Improvements in the plaque milieu                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0984 -            causes the transformation of macrophages from an                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0985 -            immobilized to a mobile state by the expression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL0986 -            dendritic cell markers (117,118) such as chemokine (C-C                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0987 -            motif) receptor 7 (CCR7), an essential requirement for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL0988 -            dendrite cell migration (119). CCR7 control of immune cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0989 -            emigration is mediated by the activation and upregulation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL0990 -            of the liver X receptor (28). The downstream target of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL0991 -            liver X receptor, ABCA1, is also unregulated (118).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0992 -            Macrophage/foam cell migration and morphological                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL0993 -            transformation can be, in part, facilitated by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL0994 -            ABCA1-induced cholesterol redistribution. ABCA1 may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0995 -            decrease membrane cholesterol pools releasing Rac-GTP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL0996 -            (120,121). ABCG1 and LDL receptor-related protein 1 may                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL0997 -            also play a small role in macrophage migration from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL0998 -            atherosclerotic plaques (119,122).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1000 -             ..
PL1001 -       24.  ENDOTHELIAL REPAIR, REGENERATION AND HOMEOSTASIS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL1002 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1003 -            Vascular ECs serve as a dynamic barrier separating the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1004 -            vessel wall from blood.  They also control vascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1005 -            homeostasis by regulating vascular tone, leukocyte                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1006 -            trafficking and vessel permeability.  Endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1007 -            dysfunction - an early hallmark of atherosclerosis - is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1008 -            characterized by the conversion of ECs from a normal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1009 -            physiological phenotype to a vasoconstrictive,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL1010 -            procoagulant, platelet-activating phenotype that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL1011 -            contributes to atherosclerosis (123,124).  Prolonged                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1012 -            endothelial dysfunction can lead to cell apoptosis, which                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1013 -            can ultimately denude the vessel wall (125,126).  To                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1014 -            achieve atherosclerotic regression, these dysfunctional ECs                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1015 -            must be returned to basal homeostasis and dead cells need                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1016 -            to be replaced.  Currently, there are three known                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1017 -            mechanisms that can result in endothelial cell replacement:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1018 -            circulating endothelial progenitor cells, local endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1019 -            cell proliferation and migration, and abrogation of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1020 -            endothelial apoptosis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1022 -             ..
PL1023 -       25.  Endothelial progenitor cells and vascular repair The term                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1024 -            "stem cell" or "progenitor cell" refers to immature cells                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1025 -            that have the ability to self-renew and differentiate into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1026 -            a variety of cell types.  Thus, these cells have the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1027 -            potential to restore the function of damaged tissues                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1028 -            (127,128).  Endothelial progenitor cells (EPCs), similar to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1029 -            all progenitor cells, are lineage specific, and comprise a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1030 -            highly heterogeneous population of cells capable of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1031 -            differentiating exclusively into ECs (129).  The majority                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1032 -            of progenitor cells mature from hemato-poietic stem cells.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1033 -            These stem cells are mainly isolated from bone marrow,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1034 -            peripheral blood and umbilical cord, but can be obtained                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1035 -            from the spleen, intestine, liver, adipose tissue and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1036 -            adventitia (130).  Regardless of their source, all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1037 -            hematopoietic stem cells are CD34+ and CD133+.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL1038 -            Hematopoietic stem cells can also produce nonerythroid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1039 -            myeloid and granulocyte-macrophage lineages, as well as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1040 -            EPCs.  Therefore, EPCs are characterized by the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL1041 -            co-expression of both hematopoietic stem cell markers and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1042 -            endothelial markers such as vascular endothelial growth                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1043 -            factor receptor-2, CD31, endothelial nitric oxide (NO)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1044 -            synthase, and vascular endothelial cadherin (130?134).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1045 -            Although hematopoietic stem cells appear to be the main                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1046 -            source of EPCs, other resident bone marrow stem cells, such                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1047 -            as mesenchymal stem cells, may generate EPCs.  In addition,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1048 -            CD14+ myeloid subsets express both the hematopoietic and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1049 -            endothelial markers, and CD14+ monocytic cells can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1050 -            differentiate into ECs (135?138).  EPCs are instrumental in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1051 -            maintaining the integrity of the vascular endothelium,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1052 -            which contribute to the regression of atherosclerotic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1053 -            plaques.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1055 -             ..
PL1056 -       26.  To obtain any benefit from nontissue resident or                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL1057 -            exogenously administered EPCs, they must be recruited by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1058 -            and migrate to the site of injury.  This process is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1059 -            orchestrated by resident cells of the injured area.  During                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1060 -            atherosclerosis, various cell types within the plaque are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1061 -            capable of mobilizing and homing EPCs to denudated vessels.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1062 -            First, EPCs are released from their source upon stimulation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1063 -            from molecular signals produced by immune cells within the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1064 -            plaque.  Activated M2 type macrophages promote vessel                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1065 -            healing through the secretion of granulocyte                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL1066 -            colony-stimulating factor (G-CSF) (139).  G-CSF facilitates                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1067 -            the release of EPCs into circulation.  In addition,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1068 -            cytokine-mediated release of proteases such as elastase,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1069 -            cathepsin G and matrix metalloproteinase (MMP)-9 discharges                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1070 -            EPCs by cleaving the adhesive interaction between EPCs and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1071 -            stromal cells (134,140).  The released EPCs are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL1072 -            subsequently homed to and mobilized by the injured area.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1073 -            An important homing signal is the chemokine stromal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1074 -            cell-derived factor-1 (SDF-1).  Under normal conditions,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1075 -            the bone marrow and many other tissues constitutively                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1076 -            express SDF-1.  The bone marrow, however, produces a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1077 -            gradient that favours the retention of EPCs.  During                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1078 -            conditions of ischemia, inflammation and hypoxia, this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1079 -            gradient is reversed by the expression of hypoxia-inducible                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1080 -            factor-1, which upregulates SDF-1 in injured tissues                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1081 -            (141?144).  In addition, NO, estrogen, HDL, vascular                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1082 -            endothelial growth factor and erythropoietin contribute to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1083 -            the increase in the plasma titre of EPCs and their                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1084 -            recruitment to the site of injury by augmenting the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1085 -            phosphatidyl-inositol-3-phosphate (PIP3)/Akt pathway                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1086 -            (145?147).  Once in the damaged area, cell adhesion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1087 -            molecules, such as P/E-selectin and ICAM-1, mediate the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1088 -            binding of EPCs to the injured endothelium (148).  In                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1089 -            severely damaged vessels, exposed matrix proteins activate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1090 -            platelets that adhere to the denuded area.  Platelet                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1091 -            activation causes microthrombi formation and the expression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1092 -            of SDF-1, targeting EPCs to the damaged endothelium.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1093 -            Moreover, EPCs potentially adhere not only to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1094 -            endothelium, but also to platelets by interacting with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1095 -            P-selectin and GPIIb integrin (149?151).  After EPC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1096 -            attachment, they differentiate into ECs under the influence                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1097 -            of the laminar shear stress of the blood (128,152).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1099 -             ..
PL1100 -       27.  Several studies have evaluated the beneficial effects of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1101 -            EPCs on CVD.  Bone marrow-derived EPCs can differentiate                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1102 -            into ECs and induce neovascularization in ischemic mouse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1103 -            tissue (153,154).  There is an inverse relationship between                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1104 -            circulating (CD34+ and CD133+) progenitor cells for both                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1105 -            modifiable and nonmodifiable atherosclerotic risk factors,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1106 -            such as smoking and age (155).  Moreover, low circulating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1107 -            levels of EPCs are found in patients who are at high risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1108 -            of developing coronary artery disease (156).  Statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1109 -            therapy, known to reduce the incidence of CVD and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1110 -            cardiovascular events, was able to increase EPC titre and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1111 -            engraftment efficiency (157,158).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1113 -             ..
PL1114 -       28.  Physical exercise increases NO and HDL production, both of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1115 -            which increase EPC recruitment and EPC levels (159?161).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1117 -             ..
PL1118 -       29.  Despite the mounting evidence implicating progenitor cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1119 -            involvement in the regression of atherosclerosis, there are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1120 -            concerns and caution has been advised.  Bone marrow-derived                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1121 -            progenitor cells have been associated with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1122 -            neovascularization and vessel remodelling, which can cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1123 -            plaque destabilization (130,162).  In addition, EPCs that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1124 -            have the osteoblast marker osteocalcin are retained within                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1125 -            the lesion for endothelial repair, but are also believed to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1126 -            lead to the induction and progression of coronary                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1127 -            calcification rather than normal endothelial repair (163).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1129 -             ..
PL1130 -       30.  EC apoptosis, migration and proliferation                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1132 -             ..
PL1133 -            As atherosclerosis persists, ECs become apoptotic, leading                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1134 -            to the denudation of the vessel wall. Apoptosis is known to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1135 -            be initiated by the activation of the death receptor and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1136 -            mitochondrial-mediated apoptotic pathways. HDL may have a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1137 -            role in preventing EC apoptosis and promoting endothelial                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1138 -            repair (164). HDL can directly or indirectly inhibit                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1139 -            endothelial apoptosis either by decreasing the levels of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1140 -            TNF-?, oxidized LDL and growth factors, or by inhibiting                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1141 -            apoptotic pathways. These anti-apoptotic properties are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1142 -            mediated by constituents within HDL. ApoA1, an important                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1143 -            protein of the RCT pathways, diminishes oxidized LDL and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1144 -            TNF-? induced apoptosis (164?166). Lysosphingolipids within                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1145 -            HDL, such as sphingosylphonphorylcholine and lysosulfatide,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1146 -            can inhibit growth factor-induced apoptosis as well as                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1147 -            directly interfere with apoptotic signalling within ECs by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1148 -            activating the Akt signalling pathways (167?169).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1150 -             ..
PL1151 -       31.  Endothelial migration and proliferation is also promoted by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1152 -            HDL. Endothelial migration is believed to be stimulated by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1153 -            the interaction between SR-BI and HDL (157).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL1154 -            Alternatively, sphingosine-1-phosphate within HDL can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1155 -            induce endothelial cell migration by activating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL1156 -            Ras/Raf1-dependent ERK (157,167). The induction of EC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1157 -            proliferation by HDL is mediated by downregulating                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1158 -            ADAMTS-1, by activating the protein kinase C pathway and by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1159 -            increasing intracellular Ca2+ levels through phospholipase                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1160 -            C activation (170?172).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1162 -             ..
PL1163 -       32.  SMOOTH MUSCLE CELL PROLIFERATION AND REGRESSION                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL1164 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1165 -            Although there are four known smooth muscle cell                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL1166 -            subpopulations (173?175), focus has been placed on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1167 -            understanding two morphologically distinct subpopulations.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1168 -            The majority of vascular smooth muscle cells (VSMCs)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1169 -            normally found in the arterial media are elongated and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1170 -            spindle shaped, forming the classic "hills and valley"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1171 -            growth pattern.  These "swirling-type" VSMCs have a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1172 -            contractile phenotype.  VSMCs with the synthetic phenotype,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1173 -            also known as the "epithelioid-type", are only present in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1174 -            small proportions within the arterial media.  The synthetic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1175 -            phenotype of VSMC is cuboidal in shape and displays a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1176 -            cobblestone appearance at confluence.  These VSMCs are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1177 -            believed to be the major VSMC contributor to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL1178 -            atherosclerotic plaque progression (176?178).  Akin to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1179 -            macrophages, accumulation of intercellular lipids can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1180 -            change VSMCs into foam cells, which may be considered a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1181 -            third important phenotype of VSMC found in atherosclerotic                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1182 -            plaques.  Moreover, de-differentiation of VSMC decreases                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1183 -            its affinity to HDL, thus effectively decreasing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PL1184 -            apo-mediated cholesterol efflux and contributing to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1185 -            early events of foam cell transformation (179).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PL1187 -             ..
PL1188 -       33.  Despite the large amount of evidence linking VSMC to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1189 -            atherosclerotic plaque progression, little is known about                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1190 -            their involvement in atherosclerotic plaque regression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1191 -            Nevertheless, regression can be induced by the removal of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1192 -            lipids from sterol-loaded VSMC and by the cessation of VSMC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1193 -            proliferation, which is accompanied by the reversal of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1194 -            pathological phenotypic modulation.  Sterol unloading from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1195 -            VSMCs shares many similarities with macrophage sterol                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1196 -            removal.  SR-BI, a mediator of cholesterol efflux in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1197 -            macrophage and influx in hepatocytes are also expressed in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1198 -            VSMCs (180).  Although synthetic VSMCs have a reduced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1199 -            affinity for NO, NO is still capable of inhibiting smooth                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1200 -            muscle cell proliferation under cell culture conditions.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1201 -            Supplementation with L-arginine, the precursor of NO, has                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1202 -            also been shown to induce plaque regression in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL1203 -            cholesterol-fed rabbits (181).  Bioactive fatty acids such                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1204 -            as prostacyclin I1 and prostaglandin E2 maintain the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1205 -            contractile phenotype of VSMCs and play a major role in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1206 -            reducing migration and proliferation of VSMCs through                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1207 -            activation of peroxisome proliferator-activated receptors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1208 -            (PPARs).  Activation of both PPAR-? and PPAR-? leads to the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1209 -            suppression of proinflammatory cytokines by inhibiting the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1210 -            activity of NF-?B (182,183).  In addition, PPAR-? inhibits                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1211 -            proliferation through a p16/pRb/E2F-mediated suppression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1212 -            telomerase activity.  PPAR-? activity inhibits VSMC                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PL1213 -            migration and proliferation by blocking the cell cycle                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1214 -            (184?186).  PPAR activation regulates lipid metabolism and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1215 -            inhibits foam cell formation by augmenting the expression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PL1216 -            of scavenger receptors (187).                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PL1218 -             ..
PL1219 -       34.  CONCLUSION                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1220 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1221 -            Nearly a half century ago, atherosclerotic plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PL1222 -            regression was considered to be an unachievable feat.  Now                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1223 -            it is recognized that established plaques can rapidly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1224 -            stabilize and regress in animals and humans.  Experimental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1225 -            data have shown that plaque regression is not simply a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1226 -            rewinding of the sequences of events that lead to lesion                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1227 -            progression, but instead involves specific cellular and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1228 -            molecular pathways that are eventually able to mobilize all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1229 -            pathological components of the plaque.  HDL, ECs and VSMCs                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1230 -            all play important roles in the progression and regression                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1231 -            of atherosclerosis.  Targeting of these cells and molecules                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1232 -            in the future will ensure pharmaceutical agents are able to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PL1233 -            elicit even better plaque regression.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1235 -                ..
PL1236 -               [On 151019 0930 Radiology report on CCTA performed on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PL1237 -               151019, indicates calcification in original bypassed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PL1238 -               arteries has increased since CABG +4 surgery on 091022;                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PL1239 -               seems conflicting with this research theorizing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PL1240 -               atherosclerosis plaques regress rapidly with elevated                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1241 -               HDL and EPCs. ref SDS 69 J14N                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1243 -                ..
PL1244 -               [On 151019 0930 an undated addendum was added to report                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PL1245 -               on CCTA test on 151019, that clarifies findings and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PL1246 -               impressions by establishing CCTA found no evidence of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1247 -               plaque, stenosis, occlusion of any kind or amount.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PL1248 -               ref SDS 69 SU4L                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PL1249 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1250 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1251 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1252 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL1253 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PL13 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     

SUBJECTS
Default Null Subject Account for Blank Record                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM03 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0401 -  ..
PM0402 - HDL Controversy Drug Induced Fails Regress Atherosclerosis Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0403 - Controversy HDL Drug Induced Fails Regress Atherosclerosis Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0404 - 
PM0405 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0406 -        Medscape Cardiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM0407 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0408 -        Medscape Medical News from the:                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0409 -        European Society of Cardiology (ESC) Congress 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PM0411 -         ..
PM0412 -        Raising HDL Cholesterol: The Controversy                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0413 -        
PM0414 -        Robert Harrington, MD; Renu Virmani, MD; Stephen Nicholls,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0415 -        MBBS, PhD                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0416 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0417 -        Date........................... October 16, 2013                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PM0418 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0419 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0420 -        1.  Introductions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PM0421 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0422 -            Robert Harrington, MD: Hi. I'm Bob Harrington from Stanford                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0423 -            University. I'm here at the European Society of Cardiology                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0424 -            (ESC) meetings in Amsterdam and have had an opportunity to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0425 -            talk with a few colleagues about some of the hot, breaking                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0426 -            science at these meetings. Joining me today is Renu Virmani,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PM0427 -            pathologist from Washington, DC. Welcome, Renu.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM0429 -             ..
PM0430 -            Renu Virmani, MD: Thank you.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PM0432 -             ..
PM0433 -            Dr Harrington: And Steve Nicholls, cardiologist from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0434 -            Adelaide, Australia, also joining us.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0436 -             ..
PM0437 -            Stephen Nicholls, MBBS, PhD: Thank you.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0439 -             ..
PM0440 -            Dr Harrington:  Now, we are having this discussion because                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0441 -            while we were sitting out there in the lunch room, there                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0442 -            was a bit of argument going around about whether raising                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0443 -            HDL is going to help our patients.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0445 -             ..
PM0446 -            You presented a trial this morning, Steve, about inducing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0447 -            ApoA.  There are a number of phase 2-type trials going on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0448 -            with direct infusion of ApoA1 or the prime constituent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0449 -            protein of HDL.  None of it has looked good so far, and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0450 -            that is where the context of the argument would be.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0452 -             ..
PM0453 -        2.  Biologics of Plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0454 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0455 -            Dr Harrington: So, Renu, I will ask you first. You are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0456 -            skeptical that giving people back HDL is going to help                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0457 -            from a cardiovascular perspective.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0459 -             ..
PM0460 -            Dr Virmani: For me, what really matters is in the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0461 -            arterial wall, the lipid that gets in.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0463 -             ..
PM0464 -            Dr Harrington: Don't we think about ApoA as a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PM0465 -            molecule that can suck out LDL from the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0466 -            plaque? I am an interventional cardiologist. I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PM0467 -            like the visual of sucking out the plaque.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0469 -             ..
PM0470 -            Dr Virmani: I think it sounds attractive. In vitro you can                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0471 -            do macrophages and you can see it suck out, but macrophages                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0472 -            have to travel to that necrotic core to be able to suck                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0473 -            out. And, you know, that surface is very rich in type 1                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0474 -            collagen; to break that is not that easy. I'm not convinced                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0475 -            that we can get macrophages there, pick it out, and then                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0476 -            take it back into the circulation.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0478 -             ..
PM0479 -            Dr Harrington: Interesting hypothesis, but you believe                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0480 -            there might be biologic mechanisms that prevent it from                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0481 -            working?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0483 -             ..
PM0484 -            Dr Virmani: Absolutely. I think biologics of the plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0485 -            itself prevent it.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0487 -             ..
PM0488 -        3.  Why HDL?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0490 -             ..
PM0491 -            Dr Harrington:  Steve, you probably have a little bit of a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0492 -            different perspective.  Before you tell us where you think                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0493 -            the field is going, review for our audience what has been                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0494 -            studied so far -- mechanisms -- and what have been the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0495 -            results.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0497 -             ..
PM0498 -            Dr Nicholls:  We could ask ourselves why we are interested                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0499 -            in HDL in the first place.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0501 -             ..
PM0502 -            Dr Harrington: Let's start there.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0504 -             ..
PM0505 -            Dr Nicholls:  The reality is that in large populations, if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0506 -            you've got low levels of HDL cholesterol, you have got a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0507 -            high risk.  We know that in animal studies, if you do                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0508 -            something to HDL -- you infuse it, you turn on one of its                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0509 -            major proteins using transgenic studies -- favorable things                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0510 -            happen to plaque models of atherosclerosis.  It has a range                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0511 -            of biological activities which, in theory, could have a                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0512 -            favorable effect on the arterial wall: lipid mobilization,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0513 -            anti-inflammatory effects, antithrombotic effects.  We                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0514 -            don't know which of them occur in vivo and whether that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0515 -            will translate to a favorable effect.  We have seen, if you                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0516 -            look at established medical therapies, that even small                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0517 -            increases in HDL cholesterol predict the benefits of the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0518 -            fibrate studies when they worked.  We have seen it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0519 -            associate with the benefit of statins.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0521 -             ..
PM0522 -        4.  Infusing HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PM0523 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0524 -            Dr Nicholls: We have seen that if you infuse HDL, you                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0525 -            rapidly regress plaque. And so that tells me that if                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0526 -            you infuse it in large enough quantities, which don't                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0527 -            necessarily raise HDL cholesterol -- and that is the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0528 -            big distinction here; the concerns with the failed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0529 -            studies have been about HDL cholesterol-raising drugs,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0530 -            and that may be different from targeting HDL -- and so                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0531 -            if you infuse HDL, give a boatload of it into the                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0532 -            plasma straight away, it seems to be doing the right                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0533 -            thing. It is shrinking plaques. Ultimately, the HDL                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0534 -            hypothesis will not be proven until an HDL drug                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM0535 -            reduces cardiovascular events, and we haven't seen                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0536 -            that yet.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0538 -             ..
PM0539 -            Dr Harrington: We really need to see an HDL infusing                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0540 -            agent in a large enough outcome study to tell us                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PM0541 -            yay or nay.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0543 -             ..
PM0544 -            Dr Nicholls:  To me, that is probably the purest                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PM0545 -            hypothesis.  You know, if you look at the other drugs that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0546 -            are out there, niacin has failed.  Niacin does lots of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0547 -            other things.  The CETP inhibitors, some of them failed                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0548 -            already; they have got some baggage.  There are 2 CETP                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0549 -            inhibitors that are very potent that are in phase 3.  They                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0550 -            double HDL but they lower LDL 30% to 40%, so they may just                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0551 -            work just because of that.  We looked at an ApoA1 inducer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0552 -            here.  It didn't work.  It didn't have any incremental                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0553 -            effect on HDL and it didn't regress plaque any more than                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0554 -            placebo.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0556 -             ..
PM0557 -            Dr Harrington: Did it have any toxic effects?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PM0559 -             ..
PM0560 -            Dr Nicholls: It raised liver enzymes a bit so I think that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0561 -            is a challenge. But that, again, doesn't become a test of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0562 -            the HDL hypothesis because it didn't do anything above and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0563 -            beyond therapy, so to me the purest test would be to infuse                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0564 -            it. We had some intriguing studies early with imaging they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0565 -            had to reformulate -- all those companies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0567 -             ..
PM0568 -            Dr Harrington: Are you talking about IVUS imaging?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0570 -             ..
PM0571 -            Dr Nicholls:  In IVUS imaging, ultimately it is going to be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0572 -            about events.  That is what we care about for our patients,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0573 -            and so we need better formulations.  But we need them to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0574 -            get to the clinical trials to evaluate them.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PM0576 -             ..
PM0577 -        5.  A Dead Hypothesis?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0578 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0579 -            Dr Harrington:  Renu, let's go back to you and mechanism,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0580 -            mechanism, mechanism.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0582 -             ..
PM0583 -            Dr Virmani:  You know, it is very nice to say that animal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0584 -            studies worked and the animal plaque resembled human plaque                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0585 -            -- absolutely not!  It is very rich in macrophages and,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0586 -            yes, you can convert, and not many necrotic cores.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0587 -            Therefore, your animal studies are not appropriate.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0588 -            Remember:  We do it with very high cholesterols and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0589 -            therefore we can reverse things in the animal.  I think                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0590 -            human [disease] is a different disease which takes decades                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0591 -            to develop, and now you want to put a regression on it and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0592 -            you are going to try and do it in a year or 2 years.  I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0593 -            just don't see how you are going to see it.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0595 -             ..
PM0596 -            Dr Nicholls:  So we saw 3 imaging studies in humans, all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0597 -            with an acute coronary syndrome within the preceding 2                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0598 -            weeks, weekly infusions of delipidated HDL on 4-6 occasions                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0599 -            over the next 2 months, rapid regression of disease.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0600 -            Whether those therapies get to the clinic or not, it at                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0601 -            least supports the hypothesis, but until we have a drug                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0602 -            that targets HDL and it reduces cardiovascular morbidity                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0603 -            and mortality, we will not have proven the hypothesis.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0605 -             ..
PM0606 -            But I think the argument, that the hypothesis is dead on                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0607 -            the basis of the evidence we have seen, is a little                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0608 -            premature.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0610 -             ..
PM0611 -            Dr Harrington:  Can I push here, Renu?  Are you saying it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0612 -            is dead or are you saying that there is still life here and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0613 -            that Steve is making some points that have to be addressed?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0615 -             ..
PM0616 -            Dr Virmani:  I think Steve is making some good points and I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0617 -            think they have to be addressed.  I totally agree that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0618 -            infusion is going to be different as compared to what is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0619 -            currently being done.  I also think that imaging with IVUS                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0620 -            has its limitations, so you cannot rely on IVUS alone.  We                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0621 -            have better tools today.  Maybe we would be able to show                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0622 -            some regression if we can show, for example, that the area                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0623 -            of cholesterol becomes much less, or if we can show by                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0624 -            optical coherence tomographythat we start seeing fewer                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0625 -            macrophages -- that will be something that will be                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
PM0626 -            encouraging, but I need that kind of encouragement.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0628 -             ..
PM0629 -        6.  PCKS9 Inhibitors                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PM0631 -             ..
PM0632 -            Dr Nicholls:  I think the other thing that we are in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0633 -            complete agreement about is that cholesterol is important.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0634 -            We have seen major advances by lowering LDL cholesterol.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0635 -            We have now got these new drugs, which are now going into                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0636 -            phase 3 trials.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM0638 -             ..
PM0639 -            Dr Harrington: Are you talking about the PCSK9                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PM0640 -            inhibitors?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0642 -             ..
PM0643 -            Dr Nicholls:  PCSK9 inhibitors.  They are going to lower                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0644 -            LDL another 50%, and it is just mind-boggling to think that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0645 -            if you get an LDL of 30, what is going to happen there?  So                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0646 -            there are 2 large outcome studies, and we have the good                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0647 -            fortune to be able to do an IVUS study in parallel and ask                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0648 -            whether we will see more regression than we have seen in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0649 -            the studies where we have been able to get LDLs to 60.  We                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0650 -            have to do the studies.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0652 -             ..
PM0653 -            Dr Harrington:  The PCSK9 story is an interesting one,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0654 -            isn't it, because it is all based on this hypothesis where                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0655 -            events decrease as LDL decreases, and what we don't know,                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0656 -            as you know well, is whether that curve plateaus.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0658 -             ..
PM0659 -        7.  Modifiable Risk                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM0660 -                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
PM0661 -            Dr Nicholls:  We talk a lot about residual risk, and I                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0662 -            think we really need to change the whole topic to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0663 -            modifiable risk.  The question is, at what point on that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0664 -            line do we stop being able to modify the risk?  We just                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0665 -            don't know that.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PM0667 -             ..
PM0668 -            Dr Harrington:  But with these new studies, as you say, it                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0669 -            is the data that has been presented thus far at these                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0670 -            meetings, at AHA, at ACC.  It is extraordinary, the effect                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0671 -            on lipids that these agents have.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0673 -             ..
PM0674 -            Dr Nicholls: Yes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
PM0676 -             ..
PM0677 -            Dr Virmani:  If you look at IVUS studies, I think it is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0678 -            interesting that with statins they can show very nicely                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0679 -            that calcium goes up.  Now, once you have high calcium, are                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0680 -            you going to be able to show a further benefit?  That is                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0681 -            going to be the problem with these.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0683 -             ..
PM0684 -            Dr Nicholls:  We looked at that data a number of years ago                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0685 -            and looked at people according to how much calcium they                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0686 -            had.  If you had a lot of calcium, you didn't progress and                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0687 -            you didn't regress.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
PM0689 -             ..
PM0690 -            Dr Virmani: Yes.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PM0692 -             ..
PM0693 -            Dr Nicholls:  They had a modifiable disease.  They have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0694 -            stable plaque.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PM0696 -             ..
PM0697 -            Dr Virmani:  That is why stable plaque, I believe, should                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
PM0698 -            not be treated percutaneously.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
PM0700 -             ..
PM0701 -            Dr Harrington:  That may be a hypothesis that we choose to                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0702 -            test, and that is an interesting question.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0704 -             ..
PM0705 -            Dr Nicholls:  One of the questions that will come with all                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0706 -            of these imaging advances is, ultimately, how we are going                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0707 -            to use it in clinical practice and whether this is exactly                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0708 -            the right way to use it.  Can we use it as a biomarker that                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0709 -            says that this person has got modifiable risk and this                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
PM0710 -            person doesn't, and so we should be more aggressive with                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0711 -            that person?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
PM0713 -                ..
PM0714 -               [on 140519 Doctor Feingold and Doctor Alba represented                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
PM0715 -               that CCTA is not effective for evaluating regression of                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0716 -               atherosclerosis plaques as a result of raising HDL 100%                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
PM0717 -               from HDL 30 to HDL 61, by hiking 11 miles per day for                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
PM0718 -               several months, because CABG x4 patients have                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
PM0719 -               established CVD that can only be treated with statin                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
PM0720 -               medications, and (2) CABG surgery changes internal                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
PM0721 -               anatomy into complexity that cannot be evaluated by CCTA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
PM0722 -               radiology technology, ref SDS 63 J83H, also set out in                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
PM0723 -               VA Progress Notes. ref SDS 63 OW49                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
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