P60910 -
P60912 - ..
P60913 - Results...
P60914 -
P60915 - Evaluation of diagnostic accuracy was based on a total of
P60916 - 14248 segments among 894 patients. Patient characteristics
P60917 - and calcium score are summarized in Table 1. 119 (0.8%)
P60918 - segments were excluded from analysis because of stent-graft
P60919 - placement; 990 (6.9%) segments were nonaccessible because
P60920 - of the anatomical variants in coronary artery. (n = 54) or
P60921 - small vessel diameter < 1.5mm (n = 936); 231(1.6%) segments
P60922 - were excluded because of motion artifact, 63 (0.4%)
P60923 - segments were excluded because of negative lumen
P60924 - manifestation.
P60926 - ..
P60927 - Does "negative lumen manifestation" mean no plaque was seen in CCTA
P60928 - scan imaging?
P60930 - ..
P60931 - In remaining 12845 segments, 4955 calcified plaques were
P60932 - detected on 3645(28.4%) segments by CCTA, of which 1769
P60933 - (35.7%) were Type I, 1248 (25.2%) type II, 947 (19.1%) Type
P60934 - III and 991 (20.0%) Type IV calcified plaque (Fig 2).
P60936 - ..
P60937 - Conclusion
P60939 - ..
P60940 - CCTA has highest accuracy in diagnosing the coronary
P60941 - artery stenosis of type I-II calcified plaques, but has a
P60942 - significant decrease in specificity, PPV and accuracy in
P60943 - type III-IV calcified plaque.
P60945 - ..
P60946 - This seems to indicate CCTA is highest accuracy finding no
P60947 - atherosclerosis plaque/stenoses, than in calculating high volumes.
P60948 -
P60949 -
P60950 -
P60951 -
P60952 -
P60953 -
P610 -
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 Hiking Duration Long Distance More Important than Speed
P70474 - HDL Lose Weight Aerobic Exercise Resolve Metabolic Syndrome
P70475 - HDL Increased with Drugs Caused Increased Cardiac Risk
P70476 - HDL Drugs Increased Caused Increased Cardiac Risk
P70477 -
P70478 -
P70479 - 2. In recent years it has become apparent that it is a gross
P70480 - oversimplification to think of HDL cholesterol as always
P70481 - being "good." Some methods of increasing HDL levels, it
P70482 - turns out, do not reduce cardiac risk. Specifically,
P70483 - several randomized clinical trials with new drugs aimed at
P70484 - increasing HDL cholesterol have been a big disappointment.
P70485 - Indeed, when HDL was increased with some of these new
P70486 - drugs, the cardiac risk was increased instead of decreased.
P70487 - (Needless to say, these drugs were never approved by the
P70488 - FDA.) So the HDL story is more complex than scientists
P70489 - originally had hoped.
P70490 -
P70491 - [...below on 131125 0005, further research reported
P70492 - that regressing plaque buildup in blood vessels
P70493 - requires elevating both HDL and endothelial projenitor
P70494 - cells (EPCs), ref SDS 0 R44O
P70496 - ..
P70497 - [...below on 131125 0005, further research reported on
P70498 - drugs that raised HDL in blood tests, fail to regress
P70499 - plaque in blood vessels, and so do not improve
P70500 - longevity. ref SDS 0 8638
P70502 - ..
P70503 - [On 151014 0900 meeting Doctor Simpson, UCSF cardiology
P70504 - researcher providing patient care at VA Medical Center
P70505 - in San Francisco; he commented that years ago drugs were
P70506 - developed that reached HDL 90; however, this did not
P70507 - achieve regression of atherosclerotic plaques.
P70508 - ref SDS 72 8Q6M
P70510 - ..
P70511 - [On 151204 1400 telecon with Doctor Vernaccia noted
P70512 - success raising HDL with drugs, but that this form of
P70513 - HDL failed to regress atherosclerotic plaques and failed
P70514 - to extend longevity. ref SDS 74 MQ7I
P70516 - ..
P70517 - [On 160405 1305 Evacetrapib raised HDL 130% failed
P70518 - clinical trial Eli Lilly cholesterol drug CEPT inhibitor
P70519 - did not reduce CV events; raised blood pressure
P70520 - (hypertension), ref SDS 79 AF51 Doctors discouraged
P70521 - Merck anacetrapib and Amgen TA-8995 which raise HDL
P70522 - similarly, expect fail to improve clinical outcomes.
P70523 - ref SDS 79 OH42
P70525 - ..
P70526 - [On 210415 0900 telecon Doctor Grunfeld at VAMCSF
P70527 - reported he and Doctor Feingold notified manufacturer's
P70528 - representative that drugs raising HDL failed to support
P70529 - Return Cholesterol Transport (RCT), and so would not
P70530 - resolve atherosclerosis. ref SDS 85 F89I
P70531 -
P70533 - ..
P70534 - 3. Fortunately, it is still true that there are several
P70535 - things we can all do to increase our HDL levels in a
P70536 - healthy way, and in a way that does appear to benefit our
P70537 - risk of heart disease.
P70538 -
P70540 - ..
P70541 - 4. How can We Increase Our HDL Levels?
P70542 -
P70543 - 1. Aerobic exercise.
P70544 -
P70545 - Many people don't like to hear it, but regular aerobic
P70546 - exercise (any exercise, such as walking, jogging or
P70547 - bike riding, that raises your heart rate for 20 to 30
P70548 - minutes at a time) may be the most effective way to
P70549 - increase HDL levels. Recent evidence suggests that the
P70550 - duration of exercise, rather than the intensity, is the
P70551 - more important factor in raising HDL choleserol. But
P70552 - any aerobic exercise helps.
P70554 - ..
P70555 - [On 210825 0827 cited in letter to Doctor Simpson
P70556 - responding to suggestion for exercising high
P70557 - intensity short duration. ref SDS 87 EA4I
P70559 - ..
P70560 - On February 13, 2021 this point is made again in another article...
P70561 -
P70562 - [On 210810 0825 CNN article reports walking best form of
P70563 - exercise for improving health. ref SDS 86 357X
P70564 -
P70565 -
P70566 - Very Well Health
P70568 - ..
P70569 - HDL Increase Longer Duration than Increase Speed
P70570 - Duration Hiking Bigger HDL Increase than Speed
P70571 - Exercise and HDL Cholesterol Levels
P70572 -
P70573 - By Richard N. Fogoros, MD
P70574 -
P70575 - Medically reviewed by Yasmine S. Ali, MD, MSCI on
P70576 - April 08, 2020
P70577 -
P70578 - https://www.verywellhealth.com/exercise-and-hdl-cholesterol-1745833
P70580 - ..
P70581 - Perhaps the most interesting finding from this study is the
P70582 - observation that it was the duration of exercise
P70583 - sessions and not the frequency or intensity of
P70584 - exercise that best correlated with increased HDL levels.
P70585 - The investigators reported that in research subjects
P70586 - exercising for at least 20 minutes, each additional
P70587 - 10-minute increase in exercise duration was associated with
P70588 - an additional 1.4 mg/dL of HDL.
P70589 -
P70590 - [On 210810 0825 CNN article reports walking best form of
P70591 - exercise for improving health. ref SDS 86~357X
P70593 - ..
P70594 - How Much Exercise Do You Need?
P70595 -
P70596 - ...increasing the duration of... exercise sessions by pacing
P70597 - yourself judiciously (that is, by going slower if necessary)
P70598 - appears to be the best way to translate exercise into higher
P70599 - HDL levels.
P70601 - ..
P70602 - This occurred in Welch increasing HDL 73 on 181029 to HDL 83 on 181112
P70603 - by hiking 192 miles in 14 day, thus averaging 12.8 miles per day?
P70605 - ..
P70606 - Why though did HDL 69 on 210118 drop to HDL 62 on 210207 after hiking
P70607 - 302 miles in 20 days, thus averaging 15 miles per day? Why didn't HDL
P70608 - increase commensurate with prior experiece to 85 or so, since the
P70609 - duration of exercise increased 117% compared to hiking in 2018?
P70611 - ..
P70612 - One striking difference was taking naproxen 250 mg x 1 pill per hike
P70613 - after getting PRP for pain management in 2018, while this increased
P70614 - 300% to 3 pills per hike without PRP, in 2021, e.g., on 210204 shown
P70615 - in case study on
P70617 - ..
P70618 - Increased hiking in 2021, was achieved in part by adding nutrition and
P70619 - hydration, which was not needed with less mileage in 2018. Nutrition
P70620 - occurred eating sandwich of rye bread, peanut butter, margarine and
P70621 - jam spaced out at miles 6, 15 and 22, and drinking 6 oz of Coca Cola
P70622 - mixed with slight amounts of lemonade at miles 6 and 15. A banana is
P70623 - eaten half at about 10 miles, and the 2nd half at 20 miles.
P70624 - Authorities have long advocated NPO for accurate lipid tests; but, in
P70625 - recent years experts have concluded this should have no effect on HDL
P70626 - test results.
P70628 - ..
P70629 - Indeed, peanut butter and Coca Cola enable noticably increased speed
P70630 - and increased distance, i.e., duration, which should increase HDL
P70631 - levels, assuming normal heart beats.
P70633 - ..
P70634 - Should try to get Erron to look at this issue scientifically.
P70635 -
P70636 -
P70637 -
P70638 -
P70640 - ..
P70641 - Article "Heart Health Center" continues...
P70643 - ..
P70644 - 2. Lose weight.
P70645 -
P70646 - Obesity results not only in increased LDL cholesterol,
P70647 - but also in reduced HDL cholesterol. If you are
P70648 - overweight, reducing your weight should increase your
P70649 - HDL levels. This is especially important if your
P70650 - excess weight is stored in your abdominal area; your
P70651 - waist-to-hip ratio is particularly important in
P70652 - determining whether you ought to concentrate on weight
P70653 - loss.
P70655 - ..
P70656 - 3. Stop smoking.
P70657 -
P70658 - If you smoke, giving up tobacco will result in an
P70659 - increase in HDL levels. (This is the only advantage I
P70660 - can think of that smokers have over non-smokers -- it
P70661 - gives them something else to do that will raise their
P70662 - HDL.)
P70664 - ..
P70665 - 4. Cut out the trans fatty acids.
P70666 -
P70667 - Trans fatty acids are currently present in many of your
P70668 - favorite prepared foods -- anything in which the
P70669 - nutrition label reads "partially hydrogenated vegetable
P70670 - oils" -- so eliminating them from the diet is not a
P70671 - trivial task. But trans fatty acids not only increase
P70672 - LDL cholesterol levels, they also reduce HDL
P70673 - cholesterol levels. Removing them from your diet will
P70674 - almost certainly result in a measurable increase in HDL
P70675 - levels. Here's more about quick and easy review of
P70676 - transfats and the heart.
P70677 -
P70678 -
P70679 -
P70680 -
P70682 - ..
P70683 - Diabetologia (1997) 40: 125?13
P70684 - Review
P70686 - ..
P70687 - Exercise and the metabolic syndrome
P70688 -
P70689 -
P70690 - https://link.springer.com/content/pdf/10.1007/s001250050653.pdf
P70691 -
P70692 - National Public Health Institute, Helsinki, Finland
P70693 - Unit for Sports and Exercise Medicine, University of Helsinki, and David Fitness & Medical Ltd, Vantaa, Finland
P70694 - 3 Helsinki University Hospital, Department of Medicine, Helsinki, Finland
P70696 - ..
P70697 - The metabolic syndrome ? also called the insulin resistance
P70698 - syndrome ? is a multifaceted syndrome characterised by five
P70699 - major abnormalities: obesity, hypertension, insulin resistance,
P70700 - glucose intolerance (impaired glucose tolerance/non-insulin-
P70701 - dependent diabetes mellitus (NIDDM)), and dyslipidaemia
P70702 - (hypertriglyceridaemia and low HDL-cholesterol).
P70703 - --------------------
P70704 -
P70706 - ..
P70707 - This was my condition HDL 30 at time of CABG x4 on 091022 0700.
P70708 - ref SDS 6 PQWU
P70710 - ..
P70711 - It might be that agent orange exposure that caused IHD with symptoms
P70712 - of atherosclerosis that required CABG x4 surgery, was a collateral
P70713 - cause of "low HDL...".
P70715 - ..
P70716 - This is partly because weight loss by exercise does not
P70717 - influence RMR in an undesirable direction [30?35]. Following
P70718 - cessation of high intensity exercise, RMR stays elevated for
P70719 - several hours. This could be due to continued increased
P70720 - substrate oxidation, increased body temperature, increased
P70721 - catecholamine levels and stimulation of protein synthesis [31,
P70722 - 36]. After interruption of exercise training, the
P70723 - exercise-induced increase in RMR returns to baseline within 3
P70724 - days [37]. This only stresses the importance of life-long
P70725 - treatment of obesity.
P70726 -
P70727 - 3 days RMR returns to baseline....
P70729 - ..
P70730 - Article continues...
P70731 -
P70732 - Dyslipidaemia associated with the metabolic syndrome is
P70733 - primarily characterised by hypertriglyceridaemia and low
P70734 - levels of HDL-cholesterol [137?139]
P70735 -
P70736 - The effects of exercise on lipid and lipoprotein profiles are
P70737 - fairly well known. Early studies emphasizing the differences
P70738 - in total cholesterol and triglycerides between individuals
P70739 - involved in endurancetype exercise and sedentary subjects, have
P70740 - been confirmed by later studies [140]. According to the
P70741 - present consensus, physically active individuals have higher
P70742 - levels of HDL- and HDL2-cholesterol and lower levels of
P70743 - triglycerides, VLDL- and dense LDL-cholesterol, compared to
P70744 - sedentary individuals [141, 142]. Furthermore, intervention
P70745 - studies have shown that unfavourable lipid and lipoprotein
P70746 - profiles respond favourably to exercise training [141, 142].
P70747 - The full significance of these findings can only be understood
P70748 - when considering the associations between lipids and
P70749 - lipoproteins, exercise and coronary heart disease morbidity and
P70750 - mortality [143?145]. Studies concerning the effect of exercise
P70751 - on lipids and lipoproteins among subjects with the metabolic
P70752 - syndrome are scarce, due to the lack of precise definition of
P70753 - the syndrome. However, it is likely that subjects with the
P70754 - metabolic syndrome would also benefit from exercise as do other
P70755 - individuals with dyslipidaemia. Exercise training increases
P70756 - the ability of muscle tissue to take up and oxidize
P70757 - non-esterified fatty acids and increases the activity of
P70758 - lipoprotein lipase (LPL) in muscle [139, 146, 147]. The
P70759 - combined effects of exercise and diet among NIDDM subjects
P70760 - resulted in a decrease in total and LDL-cholesterol, while
P70761 - HDL-cholesterol increased (for review [148]). However, it is
P70762 - difficult to separate dietary influences from the effects of
P70763 - exercise on serum lipids and lipoproteins
P70765 - ..
P70766 - Both the separate and combined effects of diet and exercise in
P70767 - reducing body weight and improving serum lipid and lipoprotein
P70768 - profiles among overweight subjects have been evaluated. Both
P70769 - treatment modalities caused significant increases in HDL-,
P70770 - HDL2- and HDL3-cholesterol and decreases in triglyceride levels
P70771 - [149]. Aerobic endurance exercise training and a lowfat diet
P70772 - can normalize the metabolic profile of obese women, even if
P70773 - their adiposity remains higher than that of lean women [150].
P70775 - ..
P70776 - In the studies by Lampman and Schteingart [151] exercise
P70777 - training alone increased insulin sensitivity, improved glucose
P70778 - tolerance, and lowered triglyceride and cholesterol levels
P70779 - among non-diabetic, non-obese subjects with
P70780 - hypertriglyceridaemia. However, these improvements did not
P70781 - occur when exercise training alone was performed by similar
P70782 - patients with impaired glucose tolerance
P70783 -
P70785 - ..
P70786 - The previous controversy regarding the beneficial metabolic
P70787 - effects of resistance training is nicely demonstrated by the
P70788 - findings of Hurley et al. [159]. High-intensity, low-volume
P70789 - training was associated with lower HDL- and higher
P70790 - LDL-cholesterol levels than in endurance trained athletes. The
P70791 - more physiologic form of resistance training, i. e.
P70792 - moderate-intensity medium-volume training again was associated
P70793 - with higher HDL- and lower LDL-cholesterol levels, levels
P70794 - comparable to those of long-distance runners.
P70795 -
P70796 -
P70797 -
P70798 -
P70799 -
P70800 -
P70801 -
P70803 - ..
P70804 - Another article discusses agent orange and HDL...
P70805 -
P70806 - National Library of Medicine
P70807 -
P70808 - Veterans and Agent Orange: Update 1998
P70809 -
P70810 - https://www.ncbi.nlm.nih.gov/books/NBK230779/#:~:text=Porphyria%20Cutanea%20Tarda,-Background
P70811 -
P70812 - 11 Other Health Effects
P70814 - ..
P70815 - Conclusions
P70816 - Strength of Evidence in Epidemiologic Studies There is
P70817 - inadequate/insufficient evidence to conclude that an
P70818 - association exists between herbicide exposure and lipid or
P70819 - lipoprotein levels. Further research is needed to better
P70820 - elucidate the small effects on HDL cholesterol and triglyceride
P70821 - concentrations observed in some studies.
P70823 - ..
P70824 - Increased Risk of Disease Among Vietnam Veterans Ranch Hand
P70825 - study data (AFHS, 1991) suggest that lipid and lipoprotein
P70826 - concentrations of Ranch Hands and comparison subjects do not
P70827 - differ overall, although significant correlation between HDL
P70828 - cholesterol (negative) or triglycerides (positive) and TCDD
P70829 - level are seen. Whether these correlations are fully
P70830 - independent of obesity is unresolved. It is concluded that
P70831 - Vietnam veterans have not experienced major lipid or
P70832 - lipoprotein disease as a result of herbicide exposure. A more
P70833 - thorough discussion of the issue of increased risk of disease
P70834 - among Vietnam veterans is contained in Chapter 1.
P70835 -
P70836 -
P70837 -
P70838 -
P70839 -
P70840 -
P70841 -
P70842 -
P709 -
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
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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 46 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
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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 -
PB05 -
SUBJECTS
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PC03 -
PC0401 - ..
PC0402 - HDL Foods Diet Liver Needs to Produce HDL
PC0403 -
PC0404 - Research found...
PC0405 -
PC0406 - Healthline
PC0407 - Foods to Increase Your HDL
PC0408 -
PC0409 - https://www.healthline.com/health/high-cholesterol/foods-to-increase-hdl
PC0411 - ..
PC0412 - Updated on November 2, 202
PC0414 - ..
PC0415 - Olives ... can lower the inflammatory impact of LDL cholesterol
PC0416 - on your body, according to research published in 2019. This
PC0417 - in turn raises HDL.
PC0418 -
PC0420 - ..
PC0421 - Eggs
PC0422 -
PC0423 - https://www.healthline.com/nutrition/how-many-eggs-should-you-eat#TOC_TITLE_HDR_3
PC0424 -
PC0425 - ...consistently raise HDL (the ?good?) cholesterol. For 70%
PC0426 - of people, there is no increase in total or LDL cholesterol.
PC0427 - Some people may experience a mild increase in a benign subtype
PC0428 - of LDL.
PC0429 -
PC0430 -
PC0432 - ..
PC0433 - The Beet
PC0435 - ..
PC0436 - 11 Foods Increase HDL Cholesterol
PC0437 -
PC0438 - Published: July 18, 2021
PC0439 -
PC0440 - https://thebeet.com/11-foods-that-can-increase-good-cholesterol/
PC0442 - ..
PC0443 - Cashews
PC0444 - 2018 study found that eating 30 grams of cashews per day for 12
PC0445 - weeks increased plasma HDL cholesterol by 1.7 mg/dL. A
PC0446 - different 2017 study also on cashews found that adding them to
PC0447 - your diet can also decrease total cholesterol and LDL
PC0448 - cholesterol levels.
PC0449 -
PC0450 -
PC0452 - ..
PC0453 - Oats
PC0454 -
PC0455 - ...bowl of oatmeal [...helps...] HDL cholesterol levels rise.
PC0456 - A 2019 review in Frontiers in Nutrition states that oat
PC0457 - beta-glucans (a type of fiber) can help to metabolize and
PC0458 - remove cholesterol from the body due to their ability to
PC0459 - enhance the elimination of bile acids. Bile acids act as a
PC0460 - warehouse for cholesterol, so eliminating them can also reduce
PC0461 - cholesterol levels. It?s recommended to aim to get in 3 grams
PC0462 - of beta-glucan, which is comparable to about ¾ cup of dry oats.
PC0463 -
PC0465 - ..
PC0466 - Avocados
PC0468 - ..
PC0469 - A 2018 review of 7 different studies found that avocado intake
PC0470 - was linked with a significant increase of HDL cholesterol, with
PC0471 - a change of about 2.84 mg/dL.
PC0472 -
PC0474 - ..
PC0475 - Beets
PC0477 - ..
PC0478 - A 2015 study found that supplementation of beetroot juice for
PC0479 - 15 days increased HDL cholesterol levels from 42.9 mg/dl to
PC0480 - 50.2 mg/dl. Researchers believe this improvement comes from
PC0481 - its dietary nitrate levels and phytochemicals.
PC0482 -
PC0483 -
PC0484 -
PC0485 -
PC0486 -
PC0487 -
PC0488 -
PC0489 -
PC0490 -
PC05 -
SUBJECTS
Default Null Subject Account for Blank Record
PD03 -
PD0401 - ..
PD0402 - Triglycerides Eggs Decrease Improve Control Arterialsclorosis Risk
PD0403 - HDL Eggs Increase Quantity Quality Control Arterialsclorosis Risk
PD0404 - Arterialsclorosis CVD Risk Eggs Increase HDL Function Triglycerides Lower
PD0405 - Eggs HDL Rise Triglycerides Decrease Improve Control CVD Risk
PD0406 -
PD0407 -
PD0408 - Pubmed
PD0409 - US National Library of Medicine National Institutes of Health
PD0411 - ..
PD0412 - Lipids. 2013 Jun;48(6):557-67. doi: 10.1007/s11745-013-3780-8.
PD0414 - ..
PD0415 - 14. Egg consumption modulates HDL lipid composition and increases
PD0416 - the cholesterol-accepting capacity of serum in metabolic
PD0417 - syndrome.
PD0418 -
PD0419 - http://www.ncbi.nlm.nih.gov/pubmed/23494579
PD0421 - ..
PD0422 - Andersen CJ, Blesso CN, Lee J, Barona J, Shah D, Thomas MJ,
PD0423 - Fernandez ML.
PD0425 - ..
PD0426 - Author information
PD0428 - ..
PD0429 - Epub 2013 Mar 15.
PD0431 - ..
PD0432 - Abstract
PD0433 -
PD0434 - 1. We recently demonstrated that daily whole egg consumption
PD0435 - during moderate carbohydrate restriction leads to greater
PD0436 - increases in plasma HDL-cholesterol (HDL-C) and
PD0437 - improvements in HDL profiles in metabolic syndrome (MetS)
PD0438 - when compared to intake of a yolk-free egg substitute.
PD0440 - ..
PD0441 - 2. We further investigated the effects of this intervention on
PD0442 - HDL composition and function, hypothesizing that the
PD0443 - phospholipid species present in egg yolk modulate HDL lipid
PD0444 - composition to increase the cholesterol-accepting capacity
PD0445 - of subject serum.
PD0447 - ..
PD0448 - 3. Men and women classified with MetS were randomly assigned
PD0449 - to consume either three whole eggs (EGG, n = 20) per day or
PD0450 - the equivalent amount of egg substitute (SUB, n = 17)
PD0451 - throughout a 12-week moderate carbohydrate-restricted
PD0452 - (25-30 % of energy) diet.
PD0454 - ..
PD0455 - 4. Relative to other HDL lipids, HDL-cholesteryl ester content
PD0456 - increased in all subjects, with greater increases in the
PD0457 - SUB group.
PD0459 - ..
PD0460 - 5. Further, HDL-triacylglycerol content was reduced in EGG
PD0461 - group subjects with normal baseline plasma HDL-C, resulting
PD0462 - in increases in HDL-CE/TAG ratios in both groups.
PD0464 - ..
PD0465 - 6. Phospholipid analysis by mass spectrometry revealed that
PD0466 - HDL became enriched in phosphatidylethanolamine in the EGG
PD0467 - group, and that EGG group HDL better reflected
PD0468 - sphingomyelin species present in the whole egg product at
PD0469 - week 12 compared to baseline.
PD0471 - ..
PD0472 - 7. Further, macrophage cholesterol efflux to EGG subject serum
PD0473 - increased from baseline to week 12, whereas no changes were
PD0474 - observed in the SUB group.
PD0476 - ..
PD0477 - 8. Together, these findings suggest that daily egg consumption
PD0478 - promotes favorable shifts in HDL lipid composition and
PD0479 - function beyond increasing plasma HDL-C in MetS. PMID:
PD0480 - 23494579 [PubMed - indexed for MEDLINE] PMCID:
PD0481 -
PD0482 - [...above on 131125 clinical study found consuming 750
PD0483 - ml orange juice per day raised HDL 21%. ref SDS 0 R48K
PD0485 - ..
PD0486 - PMC3869568 [Available on 2014/6/1]
PD0487 -
PD0488 -
PD0489 -
PD0490 -
PD0491 -
PD05 -
SUBJECTS
Default Null Subject Account for Blank Record
PE03 -
PE0401 - ..
PE0402 - LDL Pattern A > 250 AN LDL Pattern B < 250 AN Penetrate Endothelial Lining Artery
PE0403 -
PE0404 -
PE0405 - Journal of Lipid Research Volume 31, 1990
PE0406 -
PE0407 - 15. Differences in carbohydrate content of low density
PE0408 - lipoproteins associated with low density lipoprotein
PE0409 - subclass patterns
PE0411 - ..
PE0412 - Michael La Belle' and Ronald M. Krauss
PE0413 -
PE0414 - http://www.jlr.org/content/31/9/1577.full.pdf
PE0416 - ..
PE0417 - Donner Laboratory, University of California, and Molecular
PE0418 - Medicine Research Program,
PE0420 - ..
PE0421 - Research Medicine and Radiation Biophysics Division, Lawrence
PE0422 - Berkeley Laboratory, 1 Cyclotron Road, Berkeley, CA 94720
PE0424 - ..
PE0425 - Abstract
PE0427 - ..
PE0428 - The neutral carbohydrate content of both the protein (apoB) and
PE0429 - lipid fractions of low density lipoproteins (LDL) from subjects
PE0430 - with a predominance of small, dense LDL (sub- class pattern B)
PE0431 - was found to be lower than in subjects with larger LDL
PE0432 - (subclass pattern A): 45 * 12 versus 64 * 13 mg/g apoLDL, and
PE0433 - 58 * 8 versus 71 * 8 mg/g apoLDL (P<0.0005 for both). Sialic
PE0434 - acid content of LDL lipids, but not apoB, was also reduced in
PE0435 - subclass pattern B. ApoB and glycolipid carbo- hydrate content
PE0436 - of total LDL and LDL density subfractions declined with
PE0437 - increasing LDL density and decreasing particle diameter.
PE0438 - Moreover, in LDL subfractions from pattern B subjects,
PE0439 - carbohydrate content of LDL apoB, but not LDL glycolipid, was
PE0440 - significantly lower in comparison with particles of simiiar
PE0441 - size from pattern A subjects. Thus, in LDL subclass pattern B,
PE0442 - reductions in LDL carbohydrate content are associated both with
PE0443 - reduced concentrations of larger carbohydrate-enriched LDL
PE0444 - subclasses, and with reduced glycosylation of apoB in all LDL
PE0445 - particles. LDL glycolipids may vary with overall lipid con-
PE0446 - tent of LDL particles, but variation in apoB glycosylation may
PE0447 - indicate differences in pathways for LDL production, and re-
PE0448 - duced apoB glycosylation may reflect the altered metabolic
PE0449 - state responsible for LDL subclass pattern B.-La Belle, M., and
PE0450 - R M Krause. Differences in carbohydrate content of low
PE0451 - density lipoproteins associated with low density lipoprotein
PE0452 - subclass patterns. J Lipid Rcs. 1990. 31: 1577-1588.
PE0454 - ..
PE0455 - Abbreviations:
PE0456 -
PE0457 - 1. LDL, low density lipoprotein;
PE0458 - 2. apoB, apolipoprotein B;
PE0459 - 3. VLDL, very low density lipoprotein;
PE0460 - 4. IDL, intermediate density lipoprotein;
PE0461 - 5. HDL, high density lipoprotein;
PE0462 - 6. apoLDL, LDL protein;
PE0463 - 7. FH, familial hypercholesterolemia;
PE0464 - 8. kD, kdodalton;
PE0465 - 9. SDS, sodium dodecyl sulfate;
PE0466 - 10. WGA, wheat germ agglutinin;
PE0467 - 11. VNTR, variable number of terminal repeats;
PE0468 - 12. ER, endoplasmic reticulum;
PE0469 - 13. LCP, lipoprotein-complexing proteoglycan;
PE0470 - 14. BSA, bovine serum albumin.
PE0472 - ..
PE0473 - Low density lipoproteins (LDL) in humans function as the major
PE0474 - carriers of plasma cholesterol and levels of LDL cholesterol in
PE0475 - the plasma have been correlated with the risk of heart disease
PE0476 - (1, 2). In addition, a positive correla- tion has been found
PE0477 - between coronary heart disease and high levels of plasma
PE0478 - triglyceride, very low density lipo- proteins (VLDL), and
PE0479 - intermediate density lipoproteins (IDL) (3-5), while levels of
PE0480 - high density lipoprotein (HDL) choleste disease (6, 7).
PE0482 - ..
PE0483 - Earlier work has shown heterogeneity of LDL particle size,
PE0484 - density, and composition (8-16) and the existence of distinct
PE0485 - subclasses of LDL that can be identified by ultra- centrifugal
PE0486 - and gel electrophoretic techniques (13-16). Analysis of LDL by
PE0487 - gradient gel electrophoresis showed that LDL from most subjects
PE0488 - falls into one of two distinct LDL subclass patterns, A or B
PE0489 - (16, 17). LDL subclass pattern A is characterized by the
PE0490 - presence of a major LDL with a large diameter (usually greater
PE0491 - than 255 A) and a secondary LDL peak of smaller diameter, while
PE0492 - LDL subclass pattern B has a major LDL peak of smaller
PE0493 - diameter, usually less than 255 A in diameter, and a secondary
PE0494 - LDL peak of larger diameter than the major peak (Fig. 1).
PE0495 - Complex segregation analysis has shown that these LDL subclass
PE0496 - patterns are influenced by a common allele at a single genetic
PE0497 - locus (18). The pattern B-associated allele has a population
PE0498 - frequency of approximately 25% and is dominant, but with
PE0499 - reduced penetrance in young males (<20 yr) and premenopausal
PE0500 - women (17). Individuals with LDL subclass pattern B have
PE0501 - relatively increased levels of triglyceride, VLDL, and IDL and
PE0502 - decreased levels of HDL cholesterol (16-18), a profile that
PE0503 - would predict an increased risk of atherosclerosis. A
PE0504 - subsequent study of LDL subclass patterns versus risk of
PE0505 - myocardial infarction found that individuals with LDL subclass
PE0506 - pattern B have up to a threefold in- crease in risk of
PE0507 - myocardial infarction (19).
PE0508 -
PE0509 - ********************
PE0510 -
PE0511 - 269 A
PE0512 -
PE0513 - |
PE0514 - | |
PE0515 - | | 251 A
PE0516 - / \
PE0517 - | | |
PE0518 - | | / |
PE0519 - | | 263 A | |
PE0520 - / \ 264 A | |
PE0521 - / \/\ /\/ |
PE0522 - . . / \
PE0523 - . . . .
PE0524 - . . . . . . ...
PE0526 - ..
PE0527 - Fig I. Densitometric scans of plasma low density lipoprotein
PE0528 - particles electrophoresed under nondenaturing conditions on 2 %
PE0529 - to 16 % gradient gel and stained with Oil Red 0. Left: scan of
PE0530 - LDL subclass pattern A, which is characterized by a felatively
PE0531 - large major LDL peak (269 A) and a smaller diameter (263 A)
PE0532 - secondary peak. Right: scan of LDL subclass pattern B,
PE0533 - characterized by a. relatively small major LDL peak (251 A) and
PE0534 - a larger diameter (264 A) secondary LDL peak
PE0535 -
PE0536 - **********************
PE0538 - ..
PE0539 - The smaller LDL species that predominate in LDL subclass
PE0540 - pattern B have also been shown to have a higher buoyant density
PE0541 - and relatively lower 1ipid:protein ratio than the larger LDL
PE0542 - that predominate in subclass pattern A (15). The question
PE0543 - arises as to whether there are other structural differences
PE0544 - between the LDL found in subclass pattern A and B that may
PE0545 - relate to the genetic basis of the LDL subclass patterns and
PE0546 - that might contribute to differences in coronary disease risk
PE0547 - associated with these patterns. Low density lipoproteins are
PE0548 - complex macromo- lecules consisting of a core of esterified
PE0549 - cholesterol (with a small amount of triglyceride) surrounded by
PE0550 - a layer of more polar lipids (free cholesterol and
PE0551 - phospholipids) and a single large ( = 550 kD) glycoprotein,
PE0552 - apolipoprotein B (apoB). The amount of carbohydrate present on
PE0553 - apoB has been reported to range from 4% to 10% (40 to 100 mg/g
PE0554 - apoB) by weight (20-28). At least 50% of the carbohy- drate on
PE0555 - apoB is present in the form of either of two types of N-linked
PE0556 - carbohydrate chains: a high-mannose olig- osaccharide
PE0557 - containing six mannose and two N-acetyl- glucosamine residues
PE0558 - and a complex-type oligosaccharide containing two sialic acid,
PE0559 - two galactose, five mannose, and three N-acetylglucosamine
PE0560 - residues (22). In addition, other investigators report the
PE0561 - presence of high-mannose N-linked oligosaccharides composed of
PE0562 - six to nine man- nose residues and one N-acetylglucosamine
PE0563 - residue (27). The function of the carbohydrate moiety of apoB
PE0564 - in VLDL and LDL is unknown.
PE0566 - ..
PE0567 - In this study we report on differences in the carbohydrate
PE0568 - content of the LDL isolated from subjects with LDL subclass
PE0569 - pattern A or B. The results demonstrate that LDL from subjects
PE0570 - with subclass pattern B have sig- nificantly less neutral
PE0571 - carbohydrate and sialic acid than LDL from subjects with
PE0572 - subclass pattern A and that this difference is due to reduced
PE0573 - carbohydrate in both the lipid and protein fractions of the
PE0574 - pattern B LDL particles. In addition, there is a linear
PE0575 - relationship between LDL carbohydrate content and size of the
PE0576 - major LDL peak.
PE0578 - ..
PE0579 - Table 1
PE0580 -
PE0581 - Comparison of age, sex, B.M.I. (body mass index), plasma
PE0582 - triglyceride levels, cholesterol levels, and diameter of the
PE0583 - main LDL of subjects in LDL subclass pattem A versus subjects
PE0584 - in LDL subclass pattem B
PE0585 - ..
PE0586 - Particle
PE0587 - Pattern Age Sex BMI Triglycerides Total HDL LDL Diameter
PE0588 - 2
PE0589 - kg/cm
PE0590 - A
PE0591 - n = 31 21 M 24.8 97 136 46 71 263
PE0592 - 22 M 23.6 66 155 52 90 258
PE0593 - 26 M 22.0 85 174 69 88 264
PE0594 - 35 M 25.6 120 220 37 159 267
PE0595 - 37 M 20.6 50 139 61 68 263
PE0596 - 37 M 23.0 76 201 63 123 265
PE0597 - 39 M 21.3 95 206 51 136 265
PE0598 - 43 M 22.2 62 188 36 140 267
PE0599 - 45 M 22.0 47 137 47 81 275
PE0600 - 47 M 22.2 51 135 39 86 257
PE0601 - 47 M 24.0 137 194 41 126 261
PE0602 - 51 M 24.4 80 153 70 67 264
PE0603 - 57 M 20.1 132 237 61 150 262
PE0604 - 64 M 27.9 99 176 61 95 267
PE0605 - 72 M 25.4 86 183 48 118 266
PE0606 - 20 F 20.7 93 145 61 65 276
PE0607 - 24 F 20.7 47 186 72 105 275
PE0608 - 26 F 21.8 29 190 72 112 274
PE0609 - 28 F 19.0 50 184 77 97 270
PE0610 - 29 F 25.7 75 166 69 82 272
PE0611 - 29 F 22.5 87 196 77 102 265
PE0612 - 30 F 21.3 37 198 95 96 271
PE0613 - 34 F 20.4 70 248 86 148 272
PE0614 - 35 F 19.8 53 154 66 77 272
PE0615 - 35 F 20.6 92 199 69 112 262
PE0616 - 40 F 25.6 95 174 72 83 272
PE0617 - 42 F 23.3 77 235 93 127 276
PE0618 - 43 F 21.1 78 211 64 131 278
PE0619 - 44 F 21.9 76 150 36 99 262
PE0620 - 55 F 29.1 65 207 60 134 272
PE0621 - 68 F 20.0 145 253 78 146 261
PE0622 - ..
PE0623 - Average 40 22.7 79 185 62 107 267
PE0624 -
PE0626 - ..
PE0627 - B 31 M 28.4 210 217 37 138 247
PE0628 - n = 34 35 M 23.6 151 221 31 160 251
PE0629 - 35 M 23.7 179 193 29 128 248
PE0630 - 36 M 23.7 99 241 39 182 250
PE0631 - 36 M 22.0 88 146 28 100 252
PE0632 - 37 M 25.1 74 180 47 118 259
PE0633 - 39 M 21.6 170 198 44 120 248
PE0634 - 40 M 35.9 223 175 24 106 245
PE0635 - 41 M 21.0 286 222 27 138 245
PE0636 - 42 M 26.3 216 251 27 181 248
PE0637 - 43 M 27.0 396 200 37 84 246
PE0638 - 44 M 37.4 133 211 34 150 252
PE0639 - 44 M 27.6 275 288 36 197 246
PE0640 - 46 M 29.6 212 205 34 129 245
PE0641 - 46 M 23.7 263 199 35 111 242
PE0642 - 49 M 24.3 237 197 32 118 244
PE0643 - 49 M 22.7 316 294 33 198 248
PE0644 - 50 M 24.3 269 225 32 139 249
PE0645 - 51 M 27.3 104 190 49 120 259
PE0646 - 54 M 26.4 128 219 38 155 246
PE0647 - 54 M 28.3 365 190 39 78 262
PE0648 - 55 M 23.0 222 220 34 142 245
PE0649 - 56 M 23.8 187 243 52 154 249
PE0650 - 57 M 29.3 185 201 31 133 248
PE0651 - 60 M 29.6 251 173 31 92 254
PE0652 - 61 M 28.2 124 222 44 153 260
PE0653 - 68 M 32.2 217 156 22 91 242
PE0654 - 23 F 20.9 129 216 39 151 249
PE0655 - 51 F 27.3 107 261 57 183 249
PE0656 - 65 F 25.2 161 241 37 172 259
PE0657 - 67 F 25.7 180 257 41 180 258
PE0658 - 72 F 25.6 145 258 37 192 250
PE0659 - 82 F 20.7 120 240 63 153 262
PE0660 - 84 F 22.1 436 258 35 136 243
PE0661 - ..
PE0662 - Average 50 26 202 217 37 141 250
PE0663 -
PE0665 - ..
PE0666 - [...omit materials and methods...]
PE0668 - ..
PE0669 - Results
PE0671 - ..
PE0672 - Table 1 presents the clinical characteristics of the study
PE0673 - subjects, their plasma lipid levels and the diameters of their
PE0674 - predominant LDL peak as determined by nondenaturing gradient
PE0675 - gel electrophoresis. As a group, the subjects with LDL
PE0676 - subclass pattern B were older and had greater body mass than
PE0677 - the subjects with pattern A. Triglyceride, total cholesterol,
PE0678 - and LDL cholesterol were all significantly greater (P< 0.0005)
PE0679 - and HDL cholesterol levels were significantly lower (P<0.0005)
PE0680 - in the LDL subclass pattern B group than in the pattern A
PE0681 - group. These differences, as well as differences in particle
PE0682 - size of the predominant LDL species, are similar to those
PE0683 - reported previously (17, 19).
PE0685 - ..
PE0686 - Determination of the neutral carbohydrate content of isolated
PE0687 - LDL samples (Table 2) revealed significantly lower levels of
PE0688 - total LDL carbohydrate in pattern B than in pattern A
PE0689 - (P<O.O005). This difference was dye to significantly lower
PE0690 - levels of carbohydrate in both the glycolipid (P<O.O005) and
PE0691 - apoprotein (P<0.0005) components of LDL in pattern B subjects.
PE0693 - ..
PE0694 - Table 2 also shows that sialic acid content of total LDL was
PE0695 - significantly lower in subjects with LDL subclass pattern B
PE0696 - than in subjects with pattern A, by approximately one mole per
PE0697 - mole of LDL. However, sialic acid content of apoLDL,
PE0698 - determined in subgroups of 12 subjects each with LDL subclass
PE0699 - patterns A and B, was similar in the two groups: 3.2 f 0.7
PE0700 - versus 3.3 * 0.8 mol/mol apoLDL. Thus, the difference in total
PE0701 - LDL sialic content between LDL subclass patterns A and B is due
PE0702 - to the lower glycolipid content of LDL in pattern B subjects.
PE0703 - Comparison of LDL electrophoretic mobility on agarose before
PE0704 - and after exposure to neuraminidase in 10 pattern A and 9
PE0705 - pattern B subjects showed a significantly greater reduction in
PE0706 - pattern A versus pattern B mobility (54 * 4% vs 45 * 4%,
PE0707 - P<O.Ol), consistent with the presence of less sialic acid in
PE0708 - glycolipids from pattern B LDL.
PE0710 - ..
PE0711 - To determine whether the increased carbohydrate content of
PE0712 - apoLDL in subclass pattern A was due to the presence of
PE0713 - glycolipoproteins other than apoB-100, such as apoE (43), apoD
PE0714 - (44), or apoC-I11 (45), nitrocellulose blots of
PE0715 - electrophoretically separated apoLDL samples pooled from 12
PE0716 - subjects each with LDL subclass pattern A and B were stained
PE0717 - for protein or probed for glycoprotein with the biotinylated
PE0718 - lectin WGA (Fig. 2). In both samples, only a single apoB-100
PE0719 - band was visualized by each procedure. Since WGA binds
PE0720 - specifically to Nacetyl- D-glucosamine and sialic acid (42),
PE0721 - and N-acetyl- D-glucosamine is part of the core structure of
PE0722 - both high mannose and complex N-linked carbohydrate chains,
PE0723 - this result argues against the presence of significant amounts
PE0724 - of glycoproteins other than apoB-100 in the LDL preparations.
PE0726 - ..
PE0727 - Individual values for LDL carbohydrate measurements are shown
PE0728 - in Fig. 3 in relation to the particle diameter of the
PE0729 - predominant LDL subspecies on gradient gel electrophoresis.
PE0730 - Significant positive correlations with peak LDL diameter were
PE0731 - observed for total LDL carbohydrate, LDL glycolipid
PE0732 - carbohydrate, and apoLDL carbohydrate (Fig. 3A-C), consistent
PE0733 - with the mean differences between subjects with predominantly
PE0734 - smaller and larger LDL. Correlations of carbohydrate content
PE0735 - with peak LDL particle diameter within the phenotypes were not
PE0736 - statistically significant.
PE0738 - ..
PE0739 - In a subject with familial hypercholesterolemia, the peak LDL
PE0740 - particle diameter was 274 (LDL subclass pattern A) and LDL
PE0741 - carbohydrate content was 170 mg/g apoLDL (105 mg/g apoLDL in
PE0742 - protein and 65 mg/g apoLDL in lipids). In addition, sialic
PE0743 - acid content was 4.9 0.3 mol/mol LDL. These findings were all
PE0744 - consistent with those of normolipidemic subjects with LDL
PE0745 - subclass pattern A.
PE0747 - ..
PE0748 - In view of the differences in plasma lipid levels as well as
PE0749 - mean age and body mass index between subjects with differing
PE0750 - LDL subclass patterns, relationships were sought between these
PE0751 - variables and carbohydrate and sialic acid content of isolated
PE0752 - LDL. There were significant inverse correlations ( r ) of
PE0753 - carbohydrate measurements with levels of plasma triglyceride: -
PE0754 - 0.71 for glycolipid carbohydrate, - 0.57 for apoprotein
PE0755 - carbohydrate, and - 0.58 for total sialic acid (all P<O.OOl).
PE0756 - Stepwise multiple logistic regression analysis showed that LDL
PE0757 - particle diameter was a significant predictor of LDL total
PE0758 - carbohydrate, apoprotein carbohydrate, and glycolipid
PE0759 - carbohydrate content. Plasma triglyceride level contributed
PE0760 - independently but less strongly to LDL total carbohydrate and
PE0761 - glycolipid carbohydrate content, as well as to total sialic
PE0762 - acid content. Inclusion of HDL cholesterol, LDL cholesterol,
PE0763 - body mass index and age in the regression models did not change
PE0764 - these results. Fig. 4 shows the relationships of plasma
PE0765 - triglyceride concentration to LDL content of total carbohydrate
PE0766 - (Fig. 4A), apoprotein carbohydrate (Fig. 4B), and glycolipid
PE0767 - carbohydrate (Fig. 4C).
PE0769 - ..
PE0770 - HDL cholesterol concentration was positively correlated with
PE0771 - glycolipid carbohydrate (7 = 0.39) and with glycoprotein
PE0772 - carbohydrate ( r = 0.49, P<O.Ol and P< 0.001, respectively) and
PE0773 - less strongly with sialic acid ( r = 0.31, P<O.O5). LDL
PE0774 - cholesterol level showed a weak inverse correlation with LDL
PE0775 - sialic acid content ( r = - 0.32, P<0.05), but not
PE0776 - significantly with other carbohydrate parameters. Body mass
PE0777 - index was inversely correlated with LDL apoprotein carbohydrate
PE0778 - (r = - 0.39, P<O.Ol), and age was weakly correlated with
PE0779 - glycolipid carbohydrate ( r = - 0.28, P<0.05).
PE0781 - ..
PE0782 - Table 3 presents apoprotein and glycolipid carbohydrate content
PE0783 - of 11 LDL density subfractions isolated from six subjects each
PE0784 - with LDL patterns A and B. Also shown are the buoyant
PE0785 - densities and protein content of each fraction, as well as mean
PE0786 - particle diameters determined by gradient gel electrophoresis.
PE0787 - The distribution of protein mass across the density fractions
PE0788 - differed as expected between the two groups of subjects, with a
PE0789 - relative increased mass of more buoyant and larger LDL in
PE0790 - fractions 3 and 4 in subjects with pattern A (PCO.01 and P<
PE0791 - 0.05, respectively, by analysis of variance), and increased
PE0792 - mass of more dense and smaller LDL in fraction 7 in subjects
PE0793 - with pattern B (P<0.05). Both LDL particle diameter and LDL
PE0794 - glycolipid carbohydrate declined significantly with increasing
PE0795 - density of the LDL fractions, but analysis of variance showed
PE0796 - no significant differences in these variables between pattern A
PE0797 - and pattern B subjects. In contrast, analysis of variance
PE0798 - revealed significant differences of apoLDL carbohydrate content
PE0799 - both among the LDL subfractions (P< 0.0001) and between
PE0800 - subjects with LDL subclass patterns A and B (P< O.OOOl), with
PE0801 - no significant interaction between these parameters. The
PE0802 - results in Table 3 may also be compared with those shown in
PE0803 - Table 2 and Fig. 2 for apoprotein and glycolipid carbohydrate
PE0804 - content of unfractionated LDL from subjects with LDL subclass
PE0805 - patterns A and B. For subjects with pattern A, the peak
PE0806 - particle diameter (267 * 6 A, Table 1) and glycolipid and
PE0807 - apoprotein carbohydrate content (Table 2) of unfractionated LDL
PE0808 - are consistent with the size and carbohydrate content of LDL
PE0809 - particles isolated in density gradient fractions 3-6, which
PE0810 - contain the bulk of LDL mass in pattern A subjects (Table 3).
PE0811 - On the other hand, for subjects with pattern B, peak LDL
PE0812 - diameter (250 * 6, Table 1) and LDL protein and lipid
PE0813 - carbohydrate content (Table 2) of unfractionated LDL are
PE0814 - comparable to the values for LDL particles in density fractions
PE0815 - 7-9 (Table 3).
PE0817 - ..
PE0818 - Discussion
PE0820 - ..
PE0821 - Previous studies using density gradient ultracentrifugation and
PE0822 - nondenaturing gradient gel electrophoresis (13- 16) have
PE0823 - established the existence of multiple distinct subclasses of
PE0824 - plasma LDL. Differences in lipid content (15, 46-48),
PE0825 - apolipoprotein content (49, 50), and apoB immunoreactivity (32)
PE0826 - have been reported across the LDL particle spectrum. The
PE0827 - present study provides evidence that LDL carbohydrate content
PE0828 - also differs as a function of LDL diameter, since variation in
PE0829 - total LDL carbohydrate content among individuals is
PE0830 - proportional to LDL particle size as determined by
PE0831 - nondenaturing gradient gel electrophoresis. Approximately
PE0832 - one-half of the total carbohydrate is present as glycolipids,
PE0833 - and the variation in glycolipid carbohydrate appears to be
PE0834 - directly proportional to the total lipid content of LDL. Thus,
PE0835 - it is possible that LDL glycolipid content may depend on
PE0836 - metabolic events, such as lipolytic and transfer activities,
PE0837 - that affect other LDL lipids. Consistent with this is the
PE0838 - observation that plasma triglyceride level, which is related to
PE0839 - relative LDL lipid content (49), was significantly associated
PE0840 - with LDL glycolipid content.
PE0842 - ..
PE0843 - On the other hand, carbohydrate content of apoB also varies
PE0844 - over a wide range (approximately 30-100 mg/g apoLDL), and the
PE0845 - relationship of apoLDL (apoB-100) carbohydrate to peak LDL
PE0846 - particle diameter in both unfractionated LDL and LDL density
PE0847 - subfractions suggests that the previously reported differences
PE0848 - in apoB carbohydrate in the range of 40-100 mg/g apoLDL (20-28)
PE0849 - may be related in part to factors responsible for predominance
PE0850 - of LDL subclasses of varying size.
PE0852 - ..
PE0853 - The relationship of apoB carbohydrate content to LDL particle
PE0854 - size contributes to differences in apoB carbohydrate between
PE0855 - individuals with a predominant peak of larger LDL subclasses
PE0856 - (pattern A) and a major peak of smaller LDL (pattern B).
PE0857 - Previous studies have shown that these two subclass patterns
PE0858 - appear to be under the influence of a dominant gene with
PE0859 - population frequency of approximately 0.25 and full penetrance
PE0860 - in men above age 20 and in women after menopause (17, 18). The
PE0861 - present findings suggest that differences in glycosylation of
PE0862 - apoB, and possibly in glycosylation of LDL lipids, may be an
PE0863 - important feature distinguishing the LDL of individuals with
PE0864 - these two lipoprotein subclass phenotypes, and conceivably
PE0865 - could relate to the genetic determinant of these phenotypes.
PE0867 - ..
PE0868 - Reduced carbohydrate content of LDL apoB in subjects with LDL
PE0869 - subclass pattern B is not due simply to the predominance of
PE0870 - smaller, denser, carbohydrate-depleted LDL subspecies. LDL
PE0871 - particles isolated across the entire size and density range
PE0872 - from pattern B subjects showed reduced apoB carbohydrate
PE0873 - content (but no differences in glycolipid carbohydrate content)
PE0874 - in comparison with particles of comparable size and density
PE0875 - from pattern A subjects. Thus, in subjects with LDL subclass
PE0876 - pattern B, reductions in LDL apoB and glycolipid carbohydrate
PE0877 - content are associated both with reduced concentrations of more
PE0878 - buoyant, carbohydrate-enriched LDL subspecies, and with reduced
PE0879 - glycosylation of apoB in all LDL particles.
PE0881 - ..
PE0882 - Differences in apoB carbohydrate content between LDL particles
PE0883 - of differing size and density and between the two LDL subclass
PE0884 - patterns could originate with intrahepatic glycosylation of LDL
PE0885 - precursors, or could result from intravascular processing of
PE0886 - lipoprotein particles. Intravascular modification of LDL
PE0887 - glycoprotein or glycolipid could involve differential action of
PE0888 - plasma glycosidases. Plasma is known to contain a number of
PE0889 - lysosomally derived glycosidases (51-58) including alpha and
PE0890 - beta mannosidases and a neuraminidase activity. In subjects
PE0891 - with LDL subclass pattern B, there could be high activity of
PE0892 - one or more of these enzymes, or possibly greater exposure to
PE0893 - enzyme activity due to prolonged LDL plasma residence time.
PE0894 - However, with the exception of neuraminidase (pH optimum of
PE0895 - 5.5), these acid glycosidases have pH optima below pH 5.0 and,
PE0896 - based on their pH activity curves (54, 56-58), should not be
PE0897 - active at plasma pH of 7.4. In addition, kinetic studies in
PE0898 - humans with primary hypertriglyceridemia (59) have found that
PE0899 - relatively dense LDL with reduced cholesterol content typical
PE0900 - of the smaller LDL species which predominate in LDL subclass
PE0901 - pattern ?3 (15) had a higher turnover rate, and thus a shorter
PE0902 - plasma residence time than did less dense LDL. To further test
PE0903 - for a possible role of plasma residence time, we isolated LDL
PE0904 - from a subject heterozygous for familial hypercholesterolemia,
PE0905 - a condition resulting from defective or absent LDL receptors
PE0906 - and associated with reduced LDL clearance rate (60). If
PE0907 - prolonged plasma residence time were responsible for reduced
PE0908 - LDL carbohydrate content, LDL carbohydrate would be expected
PE0909 - to be reduced in such subjects. However, the
PE0910 - hypercholesterolemic subject was found to have a predominance
PE0911 - of large LDL particles and the high levels of carbohydrate
PE0912 - characteristic of pattern A LDL. Although this observation
PE0913 - will require confirmation in larger numbers of subjects, it is
PE0914 - consistent with the findings described above which suggest that
PE0915 - plasma glycoside activities are not responsible for observed
PE0916 - differences in LDL carbohydrate content between pattern A and B
PE0917 - LDL.
PE0919 - ..
PE0920 - There are several possible mechanisms by which carbohydrate
PE0921 - content of LDL precursors could be affected prior to secretion.
PE0922 - Conceivably, the glycolipid and glycoprotein differences
PE0923 - between pattern A and B LDL could be due to a variation in the
PE0924 - apoB gene. Restriction fragment length polymorphisms (RFLPs)
PE0925 - in the apoB gene have been associated with altered
PE0926 - triglyceride, cholesterol, and apoB levels (61-65) and several
PE0927 - of these RFLPs have also been found to be associated with
PE0928 - increased risk of coronary heart disease (65, 66). Examination
PE0929 - of the nucleic acid sequence of apoB (37) shows that there are
PE0930 - 19 potential sites for N-glycosidic linkage (67) and at least
PE0931 - 16 of these sites are reported to be glycosylated (68).
PE0932 - Genetic differences in apoB structure might affect the number
PE0933 - of sites available for glycosylation or the transport of apoB
PE0934 - through the Golgi apparatus with resulting differences in the
PE0935 - degree of glycosylation of both protein and lipids. Recently
PE0936 - we have used analysis of the 3' hypervariable region of the
PE0937 - apoB gene (69) in six families to exclude linkage between the
PE0938 - apoB gene and LDL subclass patterns (70). Thus variation in
PE0939 - the apoB gene does not appear to be the basis for differences
PE0940 - in LDL between subjects with LDL subclass patterns A and B.
PE0942 - ..
PE0943 - There are several steps in the post-translation processing of
PE0944 - the apoB where differences in carbohydrate could be introduced.
PE0945 - Although glycosylation begins in the rough ER during protein
PE0946 - synthesis, the majority of carbohydrate processing occurs after
PE0947 - transfer to the Golgi apparatus where further processing of the
PE0948 - oligosaccharide chains continues as the nascent glycoprotein is
PE0949 - transported from the cis Golgi through the medial and tram
PE0950 - Golgi. Since subclass pattern B LDL have less neutral
PE0951 - carbohydrate than pattern A LDL, there may be a difference in
PE0952 - transport to the tram Golgi or in oligosaccharide processing of
PE0953 - complex chains in the tram Golgi. As a result there may be
PE0954 - fewer andfor less complete carbohydrate chains present in LDL
PE0955 - from subjects with the LDL subclass pattern B phenotype.
PE0956 - Possibly such differences in Golgi processing could be
PE0957 - associated with other lipid abnormalities found in subjects
PE0958 - with LDL subclass pattern B (17, 19). Investigation of these
PE0959 - possibilities will require isolation and sequencing of
PE0960 - carbohydrate chains from both the pattern A and pattern B LDL
PE0961 - subclasses, and further information regarding mechanisms
PE0962 - involved in hepatic apoB glycosylation.
PE0964 - ..
PE0965 - Another mechanism that could contribute to the differences in
PE0966 - LDL carbohydrate between subjects with the two LDL subclass
PE0967 - patterns is differential plasma clearance of carbohydrate-rich
PE0968 - LDL. In this regard, it is interesting to note that clearance
PE0969 - of many plasma glycoproteins involves a system of receptors
PE0970 - that recognize desialylated (Le., mannose, N-acetylglucosamine,
PE0971 - or L-fucose terminated) glycoproteins (71-74). However, it is
PE0972 - unlikely that such a system accounts for the differences we
PE0973 - find since it has been reported that there are no differences
PE0974 - in catabolism of native and desialylated LDL in the pig (25) or
PE0975 - binding to skin fibroblasts (75). Further, treatment of LDL
PE0976 - with a mixture of glycosidases, which removed at least 80 7% of
PE0977 - the carbohydrate on apoB, did not affect LDL binding and uptake
PE0978 - by human fibroblasts (26). However, at present we cannot
PE0979 - exclude the possiblity that there is selective removal of LDL
PE0980 - or LDL precursors based on differences in carbohydrates other
PE0981 - than sialic acid, such as the absolute number or relative
PE0982 - content of high mannose and complex chains. Either possibility
PE0983 - could result in differential clearance rates such as those
PE0984 - reported for rat liver glycoproteins (76); those with high
PE0985 - mannose chains were cleared much more rapidly than
PE0986 - unglycosylated glycoproteins which, in turn, were cleared
PE0987 - faster than glycoproteins with the complex type carbohydrate
PE0988 - chains.
PE0990 - ..
PE0991 - Differences in clearance or catabolism of LDL with differing
PE0992 - carbohydrate content could not, however, account for the
PE0993 - presence of differing amounts of apoB glycosylation among LDL
PE0994 - particles in individual subjects. Given the evidence reviewed
PE0995 - above that these differences are likely to arise from variation
PE0996 - in intrahepatic processing of LDL precursors prior to
PE0997 - secretion, the present observation suggests that some or all of
PE0998 - the multiple discrete subclasses of LDL described in previous
PE0999 - reports arise in parallel from different hepatic precursors,
PE1000 - rather than sequentially from intravascular metabolism of a
PE1001 - common precursor. Such a conclusion is compatible with
PE1002 - previous evidence for the presence of multiple discrete VLDL
PE1003 - and IDL subclasses in human plasma (77), which in turn give
PE1004 - rise to different LDL products with in vitro lipolysis (78) and
PE1005 - intravascular metabolism in rats (79). Studies are currently
PE1006 - in progress to evaluate the possiblity that differential
PE1007 - glycosylation of apoB among these precursors corresponds to
PE1008 - differences in apoB glycosylation among their LDL products.
PE1010 - ..
PE1011 - An important question raised by this study is what role, if
PE1012 - any, differences in LDL carbohydrate content may play in the
PE1013 - increased risk of heart disease present in individuals with LDL
PE1014 - subclass pattern B (19) and a predominance of small, dense LDL
PE1015 - (26, 50).
PE1017 - ..
PE1018 - Direct interaction of LDL with components of artery walls is
PE1019 - thought to play an important role in the development of
PE1020 - atherosclerosis. Immunochemical methods have shown that apoB
PE1021 - is present in atherosclerotic lesions (80) and LDL particles,
PE1022 - in the form of insoluble proteoglycan-lipoprotein complexes,
PE1023 - have also been found to be present preferentially in these
PE1024 - lesions (80-82).
PE1026 - ..
PE1027 - A negatively charged lipoprotein-complexing proteoglycan (LCP)
PE1028 - has been isolated from human artery wall and was found to form
PE1029 - soluble and insoluble complexes with LDL (83). Initially, it
PE1030 - was found that LDL from different individuals formed different
PE1031 - amounts of insoluble complexes with LCP, with the largest
PE1032 - amount of insoluble complex formed from LDL with higher
PE1033 - affinity for LCP (84, 85). This led to the hypothesis that LDL
PE1034 - with the higher affinity for LCP could be preferentially
PE1035 - involved in the development of atherosclerosis.
PE1037 - ..
PE1038 - Later work found that the LDL population with greater affinity
PE1039 - for LCP, and the greater tendency to form insoluble LDL-LCP
PE1040 - complexes, possessed significantly less sialic acid than the
PE1041 - LDL subclass with relatively low affinity for LCP (84). In
PE1042 - addition, desialation of LDL with neuraminidase was found to
PE1043 - increase affinity of LDL for LCP (84) and, in vivo, to increase
PE1044 - uptake of LDL by the arterial intima-media (85).
PE1046 - ..
PE1047 - Based on these reports, LDL subclass pattern B LDL, with its
PE1048 - lower sialic acid content, would be predicted to show stronger
PE1049 - binding than LDL from subclass pattern A to at least one human
PE1050 - arterial proteoglycan with potential for increasing deposits of
PE1051 - an insoluble LDL-LCP complex in the arterial wall. Since we
PE1052 - have shown here that the reduction in LDL sialic content in
PE1053 - pattern B subjects is related to differences in LDL glycolipids
PE1054 - and not to apoB glycosylation, it may be that altered LDL
PE1055 - glycolipid composition could contribute to the increased risk
PE1056 - of coronary heart disease found in individuals with LDL
PE1057 - subclass pattern B.
PE1058 -
PE1059 -
PE1060 -
PE1061 -
PE11 -
SUBJECTS
Default Null Subject Account for Blank Record
PF03 -
PF0401 - ..
PF0402 - HDL Particle Count Increased with Exercise Lowers CVD Risk
PF0403 -
PF0404 -
PF0405 - Medscape
PF0406 -
PF0407 - 16. Higher HDL-Particle Concentrations Associated With Reduced CHD
PF0408 - Risk
PF0409 -
PF0410 - http://www.medscape.com/viewarticle/767250
PF0412 - ..
PF0413 - Michael O'Riordan
PF0415 - ..
PF0416 - July 11, 2012
PF0417 -
PF0418 - 1. July 11, 2012 (Pittsburgh, Pennsylvania) - A new analysis
PF0419 - of the Multi-Ethnic Study of Atherosclerosis (MESA) sheds
PF0420 - some light on the complicated association between HDL
PF0421 - cholesterol and coronary heart disease risk, with
PF0422 - researchers showing that the concentration of HDL
PF0423 - particles was independently associated with carotid
PF0424 - intima-media thickness (cIMT) and coronary heart disease
PF0425 - [1].
PF0427 - ..
PF0428 - 2. HDL cholesterol was also inversely associated with cIMT and
PF0429 - coronary heart disease events, but the association was
PF0430 - attenuated when adjusted for atherogenic lipoproteins and
PF0431 - HDL particles. In contrast, the association between
PF0432 - HDL-particle concentration and cIMT and coronary heart
PF0433 - disease risk was unaffected when adjusted for atherogenic
PF0434 - lipoproteins, HDL cholesterol, and mean HDL-particle size.
PF0436 - ..
PF0437 - 3. "Our study, essentially, wasn't measuring the cargo the HDL
PF0438 - cholesterol was carrying," lead investigator Dr Rachel
PF0439 - Mackey (University of Pittsburgh, PA) told heartwire . "As
PF0440 - we're seeing more and more puzzling results by using HDL
PF0441 - cholesterol to represent the particles, it makes a lot of
PF0442 - sense that these other atherogenic functions of HDL would
PF0443 - be better represented by how many particles there are
PF0444 - rather than by the cholesterol they carry. I'm not sure
PF0445 - there is even a biological reason to think that the
PF0446 - cholesterol they carry would be a good measure--it was
PF0447 - simply what was able to be checked."
PF0449 - ..
PF0450 - 4. The results suggest that quantification of HDL cholesterol,
PF0451 - which is the cholesterol carried by HDL particles, might
PF0452 - not "fully capture the HDL-related risk," according to the
PF0453 - researchers.
PF0455 - ..
PF0456 - 5. In an editorial accompanying the study [2], Drs Emil
PF0457 - deGoma and Daniel Rader (University of Pennsylvania,
PF0458 - Philadelphia) state that in the setting of HDL-directed
PF0459 - therapies, "a consistent inverse relationship between HDL
PF0460 - cholesterol and cardiovascular risk can no longer be
PF0461 - assumed." The independent association of HDL particles
PF0462 - with coronary heart disease suggests that it might serve
PF0463 - as a better marker of risk than HDL cholesterol and might
PF0464 - prove more useful to assess HDL-directed pharmacotherapies
PF0465 - and that increasing HDL-particle concentrations might
PF0466 - prove to be more appropriate than increasing HDL
PF0467 - cholesterol for reducing the risk of cardiovascular
PF0468 - events.
PF0470 - ..
PF0471 - 6. The results of the study and the editorial are published
PF0472 - online July 11, 2012 in the Journal of the American
PF0473 - College of Cardiology.
PF0475 - ..
PF0476 - 7. HDL Particles Measured With NMR Spectroscopy
PF0478 - ..
PF0479 - To heartwire , Mackey noted that the particle
PF0480 - concentrations of LDL, in certain populations, are a
PF0481 - better reflection of atherogenic lipoprotein particles
PF0482 - than the cholesterol carried by the LDL molecule.
PF0483 - Similarly, the HDL particles are known to have a variety
PF0484 - of functions, including carrying the cholesterol, and the
PF0485 - group hypothesized that if they measured the lipoprotein
PF0486 - particles using nuclear magnetic resonance (NMR)
PF0487 - spectroscopy it might provide a better picture of the
PF0488 - functionality of HDL. Mackey noted that HDL is a complex
PF0489 - molecule and that in addition to reverse cholesterol
PF0490 - transport, the molecule also appears to carry antioxidant
PF0491 - proteins and have anticoagulant and anti-inflammatory
PF0492 - effects.
PF0494 - ..
PF0495 - 8. Using data from the MESA study, a study of 5598 men and
PF0496 - women aged 45 to 84 years old without baseline coronary
PF0497 - heart disease, the researchers tested the associations
PF0498 - between HDL cholesterol and NMR spectroscopy-measured
PF0499 - HDL-particle numbers with cIMT and incident MI, coronary
PF0500 - heart disease death, and angina. After a mean six-year
PF0501 - follow-up, 227 coronary heart disease events were
PF0502 - documented.
PF0504 - ..
PF0505 - [On 140201 1159 obtained blood draw for Lipid NMR test
PF0506 - LDL-P at Labcor on Health Testing Centers order # 27716.
PF0507 - ref SDS 56 KQ4L
PF0509 - ..
PF0510 - 9. Overall, HDL-particle concentrations were positively
PF0511 - correlated with HDL-cholesterol levels and both had an
PF0512 - inverse correlation with LDL cholesterol, LDL particle
PF0513 - concentrations, and with other metabolic risk factors.
PF0514 - Adjusted for confounding variables, mean cIMT was lower
PF0515 - among patients with higher concentrations of HDL
PF0516 - cholesterol and HDL particles. One-standard-deviation (SD)
PF0517 - increase in the concentrations of HDL cholesterol (15
PF0518 - mg/dL) or HDL particles (6.64 µmol/L) was associated with
PF0519 - a 0.026-mm and 0.030-mm reduction in cIMT, respectively.
PF0520 - Each SD-increase in HDL cholesterol and HDL-particle
PF0521 - concentrations was also associated with a significant 26%
PF0522 - and 30% lower risk of coronary heart disease events.
PF0524 - ..
PF0525 - 10. Risk of Incident Coronary Heart Disease With 1-SD Increase
PF0526 - in HDL Cholesterol and HDL-Particle Concentration
PF0528 - ..
PF0529 - [...table omitted...]
PF0531 - ..
PF0532 - 11. The inverse relationship between HDL cholesterol and
PF0533 - coronary heart disease events and carotid atherosclerosis
PF0534 - was attenuated when separately adjusted for LDL- and
PF0535 - HDL-particle concentrations and disappeared entirely when
PF0536 - adjusted for both. On the other hand, HDL-particle
PF0537 - concentrations remained associated with cIMT and coronary
PF0538 - heart disease events after adjustment for LDL particles,
PF0539 - HDL cholesterol, or both.
PF0541 - ..
PF0542 - 12. "When we adjust for the atherogenic particle
PF0543 - [concentration] that HDL cholesterol is associated with, it
PF0544 - explains a large amount of the inverse association between
PF0545 - HDL cholesterol and outcomes," said Mackey. "It explains
PF0546 - pretty much none of the relationship between HDL particles
PF0547 - and outcomes."
PF0549 - ..
PF0550 - 13. Future Studies Need to Account for HDL-Particle Changes
PF0552 - ..
PF0553 - The assay used to measure HDL and LDL particles--which
PF0554 - detects distinct lipoprotein subclass by subjecting them to
PF0555 - electromagnetic pulses--is already commercially available,
PF0556 - the authors note. The ability to measure HDL-particle
PF0557 - concentrations does not eliminate the importance of
PF0558 - traditional lifestyle modifications known to influence HDL
PF0559 - cholesterol, however.
PF0560 -
PF0562 - ..
PF0563 - CVD Risk Requires Measuring HDL Particle Count with NMR Testing
PF0564 - Exercise HDL Particle Count Decrease Lowers CVD Risk
PF0565 - HDL Exercise Increase Particle Count Lowers CVD Risk
PF0566 - Medication Raises HDL Cholosterol But Not HDL Particle Count
PF0567 -
PF0568 -
PF0569 - 14. "So, on the one hand, for the average person, raising HDL
PF0570 - cholesterol with physical activity, smoking cessation, and
PF0571 - watching your diet is a good idea, as it should also raise
PF0572 - the HDL particles," Mackey told heartwire . "Where this
PF0573 - becomes really important is with trials focusing on
PF0574 - pharmacologically raising HDL cholesterol. We've seen
PF0575 - several where it's been raised, but HDL particles have not
PF0576 - been raised, and so we're not seeing the expected benefit.
PF0577 - Our study would suggest that as people are moving forward
PF0578 - in the HDL therapeutic area, they should pay attention to
PF0579 - what's going with the particles."
PF0581 - ..
PF0582 - 15. In their editorial, deGoma and Rader note that few studies
PF0583 - have examined the effect of existing and emerging drugs on
PF0584 - HDL-particle concentrations. A post hoc analysis of the
PF0585 - Veterans Affairs High-Density Lipoprotein Intervention
PF0586 - Trial (VA-HIT) with gemfibrozil did show on-treatment
PF0587 - HDL-particle levels were strongly associated with a
PF0588 - reduction in coronary heart disease events while HDL
PF0589 - cholesterol was not. A similar analysis of the AIM-HIGH
PF0590 - study, where extended-release niacin failed to show a
PF0591 - benefit, would be of interest, as would the effect of the
PF0592 - new cholesteryl ester-transfer protein (CETP) inhibitors on
PF0593 - HDL-particle concentrations.
PF0595 - ..
PF0596 - 16. The editorialists highlight several important questions
PF0597 - that need to be addressed in future studies. What, they
PF0598 - ask, is the biological explanation for the more robust
PF0599 - association between HDL particles and cardiovascular risk?
PF0600 - "Identifying which aspects of HDL functionality are
PF0601 - uniquely captured by [HDL particles] and not HDL
PF0602 - cholesterol represents an important next step," they write.
PF0603 - In addition, they wonder in which patients HDL-particle
PF0604 - measurements might be reasonable to help refine
PF0605 - cardiovascular risk. Calibration, discrimination, and
PF0606 - reclassification analyses will be needed to help clarify
PF0607 - the role of HDL-particle measurements above and beyond
PF0608 - traditional cardiovascular risk factors, they write.
PF0610 - ..
PF0611 - 17. This research was supported by contracts from the National
PF0612 - Heart, Lung, and Blood Institute. Mackey was supported by
PF0613 - an unrestricted research grant from LipoScience to the
PF0614 - University of Pittsburgh. Disclosures for the coauthors
PF0615 - are listed in the paper. deGoma has reported that he has no
PF0616 - relationships relevant to the contents of this paper to
PF0617 - disclose. Rader has relationships with LipoScience and
PF0618 - Vascular Strategies.
PF0619 -
PF0620 -
PF0621 -
PF0622 -
PF07 -
SUBJECTS
Default Null Subject Account for Blank Record
PG03 -
PG0401 - ..
PG0402 - HDL Large Particle Size Lowers CVD Risk
PG0403 -
PG0404 -
PG0405 - Pubmed.gov
PG0406 -
PG0407 - Atherosclerosis. 2009 Sep;206(1):276-81. doi:
PG0408 - 10.1016/j.atherosclerosis.2009.01.044. Epub 2009 Feb 12.
PG0410 - ..
PG0411 - 17. HDL particle size and the risk of coronary heart disease in
PG0412 - apparently healthy men and women: the EPIC-Norfolk prospective
PG0413 - population study.
PG0414 -
PG0415 - http://www.ncbi.nlm.nih.gov/pubmed/19268944
PG0417 - ..
PG0418 - Arsenault BJ, Lemieux I, Després JP, Gagnon P, Wareham NJ,
PG0419 - Stroes ES, Kastelein JJ, Khaw KT, Boekholdt SM.
PG0421 - ..
PG0422 - Author information
PG0424 - ..
PG0425 - Abstract
PG0426 -
PG0427 - 1. OBJECTIVE:
PG0428 -
PG0429 - To evaluate the association between HDL particle size
PG0430 - measured by gradient gel electrophoresis and risk of
PG0431 - incident coronary heart disease (CHD) in apparently healthy
PG0432 - men and women.
PG0434 - ..
PG0435 - 2. METHODS:
PG0436 -
PG0437 - We performed a prospective case-control study nested in the
PG0438 - EPIC-Norfolk cohort. Cases were apparently healthy men and
PG0439 - women aged 45-79 years who developed fatal or nonfatal CHD
PG0440 - (n=1035). They were matched to 1920 controls who remained
PG0441 - free of CHD over the follow-up period of 6 years.
PG0443 - ..
PG0444 - 3. RESULTS:
PG0445 -
PG0446 - Participants with the smallest HDL particles had the most
PG0447 - unfavourable cardiometabolic risk profile whereas those
PG0448 - with the largest HDL particles had the most favourable risk
PG0449 - profile. Plasma HDL cholesterol levels were found to be
PG0450 - the best correlate of HDL particle size (r=0.58 and r=0.62,
PG0451 - respectively, for men and women, p<0.001). Men in the
PG0452 - highest quartile of HDL particle size had an unadjusted
PG0453 - odds ratio (OR) for future CHD of 0.75 (95% CI, 0.57-0.97)
PG0454 - compared to those in the bottom quartile. For women, the
PG0455 - equivalent OR was 0.50 (0.35-0.71). After additional
PG0456 - adjustment for diabetes, body mass index, systolic blood
PG0457 - pressure, LDL and HDL cholesterol levels, the ORs were 1.43
PG0458 - (1.01-2.03) in men and 0.84 (0.52-1.35) in women.
PG0460 - ..
PG0461 - 4. CONCLUSIONS:
PG0462 -
PG0463 - A decreased HDL particle size is associated with an adverse
PG0464 - cardiometabolic risk profile. Small HDL particle size was
PG0465 - also associated with an increased CHD risk, but this
PG0466 - association was largely explained by traditional risk
PG0467 - factors.
PG0468 -
PG0469 -
PG0470 -
PG0471 -
PG0472 -
PG0473 -
PG05 -
SUBJECTS
Default Null Subject Account for Blank Record
PH03 -
PH0401 - ..
PH0402 - HDL Very Large Particle Size Increases CVD Risk
PH0403 -
PH0404 -
PH0405 - Medscape
PH0406 -
PH0407 - 18. HDL Cholesterol, HDL Particle Size and Apolipoprotein A-I:
PH0408 - Significance for Cardiovascular Risk ? The IDEAL &
PH0409 - EPIC-Norfolk Studies
PH0411 - ..
PH0412 - Wim A van der Steeg, MD, Christopher P Cannon, MD, FACC
PH0413 -
PH0414 - http://www.medscape.com/viewarticle/571347_1
PH0415 -
PH0416 - 1. Abstract
PH0417 -
PH0418 - The European Prospective Investigation into Cancer and
PH0419 - Nutrition (EPIC)-Norfolk study is part of the largest
PH0420 - prospective evaluation of diet and health ever undertaken.
PH0421 - The entire EPIC study involves more than half a million
PH0422 - people in 10 countries. The EPIC-Norfolk portion of this
PH0423 - effort is a prospective population study of 25,663 men and
PH0424 - women aged 45-79 years residing in Norfolk, United
PH0425 - Kingdom, who completed a baseline questionnaire survey and
PH0426 - attended a clinic visit.
PH0428 - ..
PH0429 - 2. EPIC should produce much more specific information about
PH0430 - the effect of diet and lifestyle on long-term health than
PH0431 - previous studies. Moreover, the database includes the
PH0432 - potential for many other studies given the detailed
PH0433 - information collected on height, weight, waist and hip
PH0434 - measurements, and blood samples stored in liquid nitrogen.
PH0435 - To date, some 100 papers have been published using the
PH0436 - EPIC-Norfolk cohort.
PH0438 - ..
PH0439 - 3. For example, the data have been used in a series of
PH0440 - studies to determine the value of lipid subfractions in
PH0441 - clinical risk assessment. In early 2007, Harchaoui and
PH0442 - colleagues reported in JACC the results of a nested
PH0443 - case-control study of EPIC-Norfolk participants.[1]
PH0444 - Several lines of evidence had suggested that small, dense
PH0445 - low-density lipoprotein (LDL) particles are more highly
PH0446 - atherogenic than larger-sized particles, yet the
PH0447 - traditional lipid profile cannot discern whether elevated
PH0448 - levels of LDL reflect small or large particles.
PH0449 - EPIC-Norfolk participants were used to find individuals
PH0450 - who developed coronary artery disease (CAD) during 6-year
PH0451 - follow-up (cases, n = 1,003) and for control subjects (n =
PH0452 - 1,885), who were matched for age, gender, and enrollment
PH0453 - time.
PH0455 - ..
PH0456 - 4. The investigators compared the ability of LDL particle
PH0457 - number (LDL-P), LDL particle size (LDL-S), and several
PH0458 - established cardiovascular risk factors to predict the
PH0459 - first cardiac event in these subjects. LDL-S correlated
PH0460 - inversely with risk for coronary artery disease, and LDL-P
PH0461 - was more predictive than LDL alone (Figure 1); however,
PH0462 - after adjusting for high-density lipoprotein cholesterol
PH0463 - (HDL-C) and triglycerides, neither test was superior. The
PH0464 - study confirmed that LDL-P and LDL-S add additional
PH0465 - information to cardiovascular risk, but little additional
PH0466 - information compared to non-HDL-C.
PH0468 - ..
PH0469 - 5. They concluded that their findings do not support routine
PH0470 - use of LDL-P in CAD risk assessment strategies for primary
PH0471 - prevention. However, the added recognition that patients
PH0472 - with low HDL-C and/or high triglycerides often have
PH0473 - elevated numbers of LDL particles without having elevated
PH0474 - LDL-C may enable their LDL-related CAD risk to be managed
PH0475 - more effectively.
PH0477 - ..
PH0478 - 6. Apolipoproteins for Risk Assessment
PH0479 -
PH0480 - So, LDL-P may play a useful role in patient management by
PH0481 - helping judge the adequacy of LDL-lowering therapy,
PH0482 - particularly among those with elevated triglycerides and
PH0483 - reduced HDL-C. Such a role also has been proposed for
PH0484 - apolipoprotein B (apo B). Indeed, both non-HDL-C and apo B
PH0485 - have been proposed as secondary treatment targets after
PH0486 - LDL-C goals have been achieved.
PH0488 - ..
PH0489 - 7. A few months after the 2007 JACC study was published, many
PH0490 - of the same investigators ? this time led by Wim A. van
PH0491 - der Steeg, MD ? published a paper looking at the role of
PH0492 - the apo B-apolipoprotein A-I (apo B-apo A-I) ratio in
PH0493 - cardiovascular risk assessment.[2] Prior to this analysis,
PH0494 - recent studies had shown that the apo B apoA-I ratio was
PH0495 - strongly associated with future CAD. This association and
PH0496 - the ability to measure apolipoprotein in nonfasting blood
PH0497 - samples had led to recommendations that the apo B-apo A-I
PH0498 - ratio be used in routine clinical care,[3] despite the
PH0499 - fact that it was not known whether this ratio is better
PH0500 - than traditional lipid values for risk assessment and
PH0501 - prediction and whether it adds predictive value to the
PH0502 - Framingham risk score.
PH0504 - ..
PH0505 - 8. The EPIC-Norfolk investigation was used to select cases,
PH0506 - who were apparently healthy men and women (45 to 79 years
PH0507 - of age) who developed fatal or nonfatal CAD (n = 869), and
PH0508 - controls (n = 1,511), who were persons without CAD and
PH0509 - again were matched for age, sex, and enrollment period.
PH0510 - (Note: Few people with diabetes and no one using
PH0511 - lipid-lowering medication participated in the study.) The
PH0512 - apo B-apo A-I ratio was associated with future CAD events,
PH0513 - independent of traditional lipid values (adjusted odds
PH0514 - ratio, 1.85 [95% CI, 1.15 to 2.98]), including the total
PH0515 - cholesterol-HDL-C ratio, and independent of the Framingham
PH0516 - risk score (adjusted odds ratio, 1.77 [CI, 1.31 to 2.39]).
PH0518 - ..
PH0519 - 9. However, it did no better than lipid values at
PH0520 - discriminating between CAD cases and controls and added
PH0521 - little to the predictive value of the Framingham risk
PH0522 - score. Moreover, it incorrectly classified 41.1% of cases
PH0523 - and 50.4% of controls.
PH0525 - ..
PH0526 - 10. In the February 12th, 2008 issue of JACC, van der Steeg et
PH0527 - al. assessed the relationships of plasma HDL-C and HDL
PH0528 - particle size with CAD risk, with a particular emphasis on
PH0529 - very high values of these parameters.[4] They also
PH0530 - evaluated the relationship for apoA-I. This post-hoc
PH0531 - analysis used data from the EPIC-Norfolk study as well as
PH0532 - the large Incremental Decrease in End Points through
PH0533 - Aggressive Lipid Lowering (IDEAL) trial (n = 8,888), which
PH0534 - compared the efficacy of high-dose to usual-dose statin
PH0535 - treatment for the secondary prevention of cardiovascular
PH0536 - events (Figure 2).[5] The IDEAL dataset contained data on
PH0537 - HDL-C and apoA-I, whereas the EPIC-Norfolk dataset (858
PH0538 - cases, 1,491 control patients) additionally had values of
PH0539 - HDL particle size as measured by nuclear magnetic resonance
PH0540 - (NMR) spectroscopy.
PH0542 - ..
PH0543 - 11. When researchers adjusted for levels of apo B and apo A-I,
PH0544 - very high values of HDL-C (>70 mg/dl) and HDL particle
PH0545 - size (>9.5 nm) were associated with increased risk of CAD
PH0546 - (Figure 3 and Figure 4). These results suggest that large
PH0547 - HDL particles increase cardiac risk, possibly by serving
PH0548 - as cholesterol donors rather than scavengers.
PH0550 - ..
PH0551 - 12. This summary, prepared for Cardiosource by Wim A van der
PH0552 - Steeg, MD, of the University of Amsterdam, Amsterdam,
PH0553 - Netherlands, discusses this new study in JACC and how the
PH0554 - observations may have important consequences for future CAD
PH0555 - risk assessment and novel treatment strategies.
PH0557 - ..
PH0558 - 13. Summary
PH0560 - ..
PH0561 - High plasma levels of high-density lipoprotein cholesterol
PH0562 - (HDL-C) are inversely related to the risk of coronary
PH0563 - artery disease (CAD).[6,7] For apolipoprotein A-I (apo
PH0564 - A-I), which is the main protein constituent of the HDL
PH0565 - particle, identical results have been reported.[8] These
PH0566 - observations have led to the development of novel
PH0567 - therapies that raise plasma levels of HDL-C or apoA-I in
PH0568 - order to further decrease risk of CAD.
PH0570 - ..
PH0571 - 14. Recently, a couple of clinical studies were published,
PH0572 - evaluating the effect of elevation of plasma HDL-C levels
PH0573 - via torcetrapib, which is an inhibitor of the cholesteryl
PH0574 - ester transfer protein.[9-12] In these studies,
PH0575 - considerable increases of plasma HDL-C and apoA-I were
PH0576 - observed in patients receiving torcetrapib. Nevertheless,
PH0577 - torcetrapib did not induce the expected regression of
PH0578 - atherosclerosis. In fact, an increase of atherosclerosis
PH0579 - was observed.
PH0581 - ..
PH0582 - This aligns with clinical trials finding HDL elevated using drugs has
PH0583 - not yielded regression of atherosclerosis, also reported above.
PH0584 - ref SDS 0 KG9F
PH0585 -
PH0586 - [On 210415 0900 telecon Doctor Grunfeld at VAMCSF reported
PH0587 - he and Doctor Feingold notified manufacturer's
PH0588 - representative that drugs raising HDL failed to support
PH0589 - Return Cholesterol Transport (RCT), and so would not
PH0590 - resolve atherosclerosis. ref SDS 85 F89I
PH0592 - ..
PH0593 - Article continues...
PH0594 -
PH0595 - 15. As extensively discussed in literature, this unexpected
PH0596 - outcome is hypothesized to relate to the rise of systolic
PH0597 - blood pressure observed in patients receiving torcetrapib.
PH0598 - However, a second possible explanation pertains to the
PH0599 - structural changes of the HDL particle induced by CETP
PH0600 - inhibition. In fact, it has been hypothesised that the
PH0601 - very large HDL particles, which become predominant when
PH0602 - HDL-C levels rise upon CETP inhibition, may be less
PH0603 - effective in exerting antiatherogenic functions.
PH0605 - ..
PH0606 - 16. This would suggest that the previously reported inverse
PH0607 - relationships of HDL-C and apo A-I with CAD do not hold
PH0608 - true for very high levels of these parameters. Therefore,
PH0609 - the present study was conducted to reassess the
PH0610 - relationship of HDL-C, HDL particle size and apo A-I with
PH0611 - the occurrence of CAD, with a focus on the effect of very
PH0612 - high values of these parameters.
PH0614 - ..
PH0615 - 17. To accomplish this, we performed a post-hoc analysis of
PH0616 - two prospective studies: the Incremental Decrease in End
PH0617 - Points through Aggressive Lipid Lowering (IDEAL) trial
PH0618 - (n=8,888) comparing the efficacy of high-dose to
PH0619 - usual-dose statin treatment for the secondary prevention
PH0620 - of cardiovascular events,[4] and the European Prospective
PH0621 - Investigation into Cancer and Nutrition (EPIC)-Norfolk
PH0622 - case-control study, including apparently healthy
PH0623 - individuals who did (cases, n=858) or did not (controls,
PH0624 - n=1,491) develop CAD during follow-up.[4] In IDEAL, only
PH0625 - HDL-C and apo A-I were available; in EPIC-Norfolk, HDL
PH0626 - particle sizes determined by nuclear magnetic resonance
PH0627 - (NMR) were also available.
PH0629 - ..
PH0630 - 18. The occurrence of a major adverse coronary event (MACE)
PH0631 - was selected as the outcome variable for this analysis. In
PH0632 - the IDEAL study, this was the primary endpoint, defined as
PH0633 - coronary death, non-fatal myocardial infarction, or
PH0634 - resuscitation after cardiac arrest. In EPIC-Norfolk, MACE
PH0635 - included fatal or nonfatal CAD, defined as codes 410-414
PH0636 - according to the International Classification of Diseases,
PH0637 - 9th revision.
PH0639 - ..
PH0640 - 19. In the IDEAL dataset, the relationships of HDL-C and apo
PH0641 - A-I with MACE were calculated by a Cox proportional
PH0642 - hazards model, yielding values for relative risk (RR) for
PH0643 - a one standard deviation (SD) increase of HDL-C or apo
PH0644 - A-I. The basic regression model included covariates for
PH0645 - age, sex, and smoking status (current, former, never)
PH0646 - recorded at baseline. Body mass index (BMI) was not taken
PH0647 - into account because this parameter did not significantly
PH0648 - contribute to the regression models. Data on alcohol
PH0649 - consumption were not available in the IDEAL database.
PH0651 - ..
PH0652 - 20. In EPIC-Norfolk, the relationships of HDL-C, HDL particle
PH0653 - size, and apo A-I with MACE were determined by conditional
PH0654 - logistic regression analysis that took into account the
PH0655 - matching for age, gender, and enrollment period, and
PH0656 - included the covariates smoking status (current, former,
PH0657 - never), BMI, and alcohol consumption (number of units per
PH0658 - week) (basic model). MACE risk estimates were expressed as
PH0659 - odds ratios (OR) for a one SD increase of HDL-C, HDL
PH0660 - particle size, or apo A-I, with 95% confidence intervals.
PH0662 - ..
PH0663 - 21. When HDL-C and HDL particle size were evaluated, the
PH0664 - regression models were additionally adjusted for
PH0665 - confounding by apo A-I. When apo A-I was evaluated,
PH0666 - additional adjustment was performed for HDL-C or HDL
PH0667 - particle size. Finally, all statistical models included apo
PH0668 - B to account for differences in the proatherogenic
PH0669 - lipoprotein fraction.
PH0671 - ..
PH0672 - 22. In the IDEAL study, we observed that plasma levels of HDL-C
PH0673 - were indeed inversely related to MACE following adjustment
PH0674 - for the basic covariates as well as for apo A-I and apo B.
PH0675 - However, at very high levels of HDL-C (>70 mg/dL), this
PH0676 - inverse relationship disappeared. In fact, HDL-C turned out
PH0677 - to be a statistically significant risk factor at these high
PH0678 - values.
PH0680 - ..
PH0681 - 23. Identical results were obtained for HDL particle size in
PH0682 - EPIC-Norfolk. This parameter was inversely related to the
PH0683 - occurrence of MACE, but turned to a significant risk factor
PH0684 - in the tail of its distribution upon adjustment for the
PH0685 - basic covariates and apo A-I and apo B. In contrast, apo
PH0686 - A-I remained negatively associated across the major part of
PH0687 - its distribution in both studies.
PH0689 - ..
PH0690 - 24. These data demonstrate that when apoA-I and apoB are kept
PH0691 - constant, HDL-C and HDL particle size may confer risk at
PH0692 - very high values. This may suggest that the unexpected
PH0693 - outcome of the torcetrapib trials indeed results from
PH0694 - factors related to the induced increase of HDL-C or the
PH0695 - size of this lipoprotein. However, additional studies are
PH0696 - required to further substantiate this hypothesis.
PH0698 - ..
PH0699 - 25. There is no clear biological explanation how HDL can become
PH0700 - proatherogenic. This only permits speculation when it
PH0701 - comes to biological mechanisms for our observations.
PH0702 - First, some of the exchange of cholesterol esters between
PH0703 - HDL and peripheral cells is known to be bidirectional, in
PH0704 - part mediated by the scavenger receptor class B1.[13]
PH0706 - ..
PH0707 - 26. This observation gives rise to the hypothesis that very
PH0708 - large HDL, which are cholesterol enriched, may at some
PH0709 - point become a cholesterol donor instead of an acceptor.
PH0710 - Second, although it has widely been acknowledged that the
PH0711 - anti-inflammatory capacity of HDL contributes to its
PH0712 - antiatherogenic potency, several studies have demonstrated
PH0713 - that HDL can also turn into a proinflammatory particle.[14]
PH0714 - Possibly, via these two latter mechanisms, a very high
PH0715 - plasma concentration of large HDL particles might in fact
PH0716 - induce a proatherogenic lipoprotein profile. However,
PH0717 - whether any of these two mechanisms has any physiological
PH0718 - relevance in humans needs certainly to be confirmed in
PH0719 - further studies.
PH0721 - ..
PH0722 - 27. Guidelines: Executive summary of the third report of the
PH0723 - National Cholesterol Education Program (NCEP) expert panel
PH0724 - on detection, evaluation, and treatment of high blood
PH0725 - cholesterol in adults (Adult Treatment Panel III). JAMA
PH0726 - 2001;285:2486-97.
PH0728 - ..
PH0729 - 28. Grundy SM, Cleeman JI, Merz CN; Coordinating Committee of
PH0730 - the National Cholesterol Education Program. Implications of
PH0731 - recent clinical trials for the National Cholesterol
PH0732 - Education Program Adult Treatment Panel III Guidelines. J
PH0733 - Am Coll Cardiol 2004;44:720-32.
PH0734 -
PH0735 -
PH0736 -
PH0738 - ..
PH0739 - Very High HDL May Increase Risk Heart Attack and Death
PH0740 - HDL Very High May Increase Risk Heart Attack and Death
PH0741 -
PH0742 - Another article says...
PH0743 -
PH0744 - Science News
PH0746 - ..
PH0747 - Too much of a good thing? Very high levels of 'good'
PH0748 - cholesterol may be harmful
PH0749 - ----------------------------------------------------
PH0750 - August 25, 2018
PH0751 - Source: European Society of Cardiology
PH0752 -
PH0754 - ..
PH0755 - Summary:
PH0757 - ..
PH0758 - New research shows that very high levels of high-density
PH0759 - lipoprotein (HDL or 'good') cholesterol may be associated
PH0760 - with an increased risk of heart attack and death.
PH0762 - ..
PH0763 - Very high levels of high-density lipoprotein (HDL or
PH0764 - "good") cholesterol may be associated with an increased
PH0765 - risk of heart attack and death, according to research
PH0766 - presented today at ESC Congress 2018.
PH0767 -
PH0768 - https://www.sciencedaily.com/releases/2018/08/180825081724.htm
PH0770 - ..
PH0771 - Study author Dr Marc Allard-Ratick, of Emory University
PH0772 - School of Medicine, Atlanta, US, said: "It may be time to
PH0773 - change the way we view HDL cholesterol. Traditionally,
PH0774 - physicians have told their patients that the higher your
PH0775 - 'good' cholesterol, the better. However, the results from
PH0776 - this study and others suggest that this may no longer be
PH0777 - the case."
PH0779 - ..
PH0780 - HDL cholesterol has been considered "good" because the HDL
PH0781 - molecule is involved in the transport of cholesterol from
PH0782 - the blood and blood vessel walls to the liver and
PH0783 - ultimately out of the body, thereby reducing the risk of
PH0784 - clogged arteries and atherosclerosis. People with low HDL
PH0785 - cholesterol have a greater risk of atherosclerosis and
PH0786 - cardiovascular disease. But the protective effect of very
PH0787 - high HDL cholesterol has been unclear.
PH0789 - ..
PH0790 - This study, conducted as part of the Emory Cardiovascular
PH0791 - Biobank, investigated the relationship between HDL
PH0792 - cholesterol levels and the risk of heart attack and death
PH0793 - in 5,965 individuals, most of whom had heart disease. The
PH0794 - average age of participants was 63 years and 35% were
PH0795 - female.
PH0797 - ..
PH0798 - Participants were divided into five groups according to
PH0799 - their HDL cholesterol level: less than 30 mg/dl (0.78
PH0800 - mmol/L), 31-40 mg/dl (0.8-1 mmol/L); 41-50 mg/dl (1.1-1.3
PH0801 - mmol/L); 51-60 mg/dl (1.3-1.5 mmol/L); and greater than 60
PH0802 - mg/dl (1.5 mmol/L).
PH0804 - ..
PH0805 - During a median follow-up of four years, 769 (13%)
PH0806 - participants had a heart attack or died from a
PH0807 - cardiovascular cause. Participants with HDL cholesterol
PH0808 - 41-60 mg/dl (1.1-1.5 mmol/L) had the lowest risk of heart
PH0809 - attack or cardiovascular death. Risk was increased both in
PH0810 - participants with low levels (less than 41 mg/dl) and very
PH0811 - high levels (greater than 60 mg/dl) of HDL cholesterol,
PH0812 - which produced a U-shaped curve when plotted graphically.
PH0814 - ..
PH0815 - Participants with HDL cholesterol levels greater than 60
PH0816 - mg/dl (1.5 mmol/L) had a nearly 50% increased risk of dying
PH0817 - from a cardiovascular cause or having a heart attack
PH0818 - compared to those with HDL cholesterol levels 41-60 mg/dl
PH0819 - (1.1-1.5 mmol/L).
PH0821 - ..
PH0822 - The associations were consistent even after controlling for
PH0823 - other risk factors for heart disease such as diabetes,
PH0824 - smoking, and low-density lipoprotein (LDL or "bad")
PH0825 - cholesterol, as well as other factors linked with high HDL
PH0826 - cholesterol such as alcohol intake, race, and sex.
PH0828 - ..
PH0829 - The results support findings from several large
PH0830 - population-based studies, including a recent publication
PH0831 - which found increased cardiovascular and all-cause death
PH0832 - when HDL cholesterol reached extremely high levels.2 Dr
PH0833 - Allard-Ratick said: "Our results are important because they
PH0834 - contribute to a steadily growing body of evidence that very
PH0835 - high HDL cholesterol levels may not be protective, and
PH0836 - because unlike much of the other data available at this
PH0837 - time, this study was conducted primarily in patients with
PH0838 - established heart disease."
PH0840 - ..
PH0841 - He noted that more research is needed to elucidate the
PH0842 - mechanisms of this paradoxical association. "While the
PH0843 - answer remains unknown, one possible explanation is that
PH0844 - extremely elevated HDL cholesterol may represent
PH0845 - 'dysfunctional HDL' which may promote rather than protect
PH0846 - against cardiovascular disease," he said.
PH0848 - ..
PH0849 - Dr Allard-Ratick concluded: "One thing is certain: the
PH0850 - mantra of HDL cholesterol as the 'good' cholesterol may no
PH0851 - longer be the case for everyone."
PH0852 -
PH0853 -
PH0854 -
PH09 -
SUBJECTS
Default Null Subject Account for Blank Record
PI03 -
PI0401 - ..
PI0402 - Statins Can Lower HDL - Atorvastatin
PI0403 - HDL Lowered by Statins - Atorvastatin
PI0404 -
PI0405 -
PI0406 - Blood by the American Society of Hematology
PI0407 -
PI0409 - ..
PI0410 - The Effects of Atorvastatin on Hematological and Inflammatory
PI0411 - Parameters.
PI0412 -
PI0413 - https://ashpublications.org/blood/article/112/11/1548/60400/The-Effects-of-Atorvastatin-on-Hematological-and
PI0415 - ..
PI0416 - Blood (2008) 112 (11): 1548.
PI0418 - ..
PI0419 - Abstract
PI0421 - ..
PI0422 - Background: Chronic inflammation may play role in the
PI0423 - development of atherosclerosis and its complications. In
PI0424 - hypercholesterolemia, the evidences of chronic inflammation
PI0425 - such as the stimulation of chemokines and cytokines, increase
PI0426 - in endothelial adhesion molecules, and the immune reactions
PI0427 - against oxidants on lipoproteins are detected. It was shown
PI0428 - that statins had some beneficial effects on lipids, thrombosis,
PI0429 - endothelial dysfunction, and smooth muscle proliferation.
PI0431 - ..
PI0432 - Aim: To investigate the effects of atorvastatin on
PI0433 - hematological and inflammatory parameters in prospective study.
PI0435 - ..
PI0436 - Material and methods: Forty patients (14 male and 26 female)
PI0437 - with primary hypercholesterolemia were treated with 20 mg/day
PI0438 - atorvastatin for 12 weeks, according to Adult Treatment Panel
PI0439 - for Third Report of National Cholesterol Education Program.
PI0440 - All patients received a detailed description of this study and
PI0441 - signed consent prior to enrollment. National and local ethical
PI0442 - committees approved this study. The exclusion criteria were
PI0443 - secondary hypercholesterolemia, acute coronary syndromes,
PI0444 - liver and renal dysfunctions, diabetes mellitus, acute/chronic
PI0445 - infection and inflammatory diseases, pregnancy, lactation,
PI0446 - malignancy, and tendency to bleeding. At baseline, and 12th
PI0447 - weeks, lipid levels such as low-density lipoprotein
PI0448 - cholesterol (LDL-C), total cholesterol (TC), high-density
PI0449 - lipoprotein cholesterol (HDL-C), very-low-density lipoprotein
PI0450 - cholesterol (VLDL-C), triglycerides (TGs), and hematological
PI0451 - parameters such as whole blood cell counts, hemoglobin and
PI0452 - fibrinogen levels, CD3, CD4, CD5, CD8, CD14, CD16, CD19, CD40,
PI0453 - CD45 using flow-cytometry, inflammatory parameters such as
PI0454 - interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor-alpha
PI0455 - (TNF-a), interferon-gamma, soluble CD-40, intracellular
PI0456 - adhesion molecule-1 (ICAM-1), vascular cell adhesion
PI0457 - molecule-1, high-sensitive CRP, sedimentation rate, and
PI0458 - enzymes including CK, AST, ALT were evaluated. The results
PI0459 - were compared with two-paired student?s-t test.
PI0461 - ..
PI0462 - Results: At the end of study, atorvastatin decreased TC
PI0463 - (p<0.001), LDL-C (p<0.001), TGs (p=0.006), VLDL-C (p=0.012),
PI0464 - and HDL-C (p<0.001). While absolute lymphocyte (p=0.003) and
PI0465 - platelet counts (p=0.001) were decreased with atorvastatin
PI0466 - treatment, absolute monocyte count increased (p=0.002). On
PI0467 - flow-cytometric examination, the expressions of CD14 (p=0.015)
PI0468 - and CD19 (p=0.039) on lymphocytes were decreased with
PI0469 - atorvastatin. Moreover, atorvastatin decreased the levels of
PI0470 - TNF-a (p<0.001), sCD40 (p<0.001), ICAM-1 (p<0.001), and IL-18
PI0471 - (p=0.024). ALT increased at the end of treatment (p=0.041).
PI0472 - But important adverse events were not seen in the patients.
PI0474 - ..
PI0475 - Conclusion: The anti-platelet and anti-inflammatory effects of
PI0476 - atorvastatin, independent from lipid-lowering effects, may play
PI0477 - an important role on the prevention of atherosclerosis, in
PI0478 - addition to its beneficial effects on lipid parameters.
PI0479 -
PI0480 -
PI0482 - ..
PI0483 - Another study reported...
PI0484 -
PI0485 - Springer Nature
PI0487 - ..
PI0488 - Association Between Paradoxical HDL Cholesterol Decrease and
PI0489 - Risk of Major Adverse Cardiovascular Events in Patients
PI0490 - Initiated on Statin Treatment in a Primary Care Setting
PI0491 -
PI0492 - https://link.springer.com/article/10.1007/s40261-015-0372-9
PI0494 - ..
PI0495 - Published: 30 December 2015
PI0496 -
PI0498 - ..
PI0499 - Abstract
PI0500 - Background and Objectives
PI0502 - ..
PI0503 - Statin-induced changes in high-density lipoprotein cholesterol
PI0504 - (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are
PI0505 - unrelated. Many patients initiated on statins experience a
PI0506 - paradoxical decrease in HDL-C. The aim of this study was to
PI0507 - evaluate the association between a decrease in HDL-C and risk
PI0508 - of major adverse cardiovascular events (MACE).
PI0509 - -----------------------------------
PI0511 - ..
PI0512 - Results
PI0514 - ..
PI0515 - HDL-C decreased in 20 %, was unchanged in 58%, and increased in
PI0516 - 22 % of patients initiated on statin treatment (96 % treated
PI0517 - with simvastatin). The propensity score-matched sample
PI0518 - comprised 5950 patients with mean baseline HDL-C and LDL-C of
PI0519 - 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was
PI0520 - associated with 56 % higher MACE risk (hazard ratio 1.56; 95 %
PI0521 - confidence interval 1.122.16; p < 0.01) compared with the
PI0522 - unchanged HDL-C group.
PI0524 - ..
PI0525 - Conclusions
PI0527 - ..
PI0528 - Paradoxical statin-induced reduction in HDL-C was relatively
PI0529 - common and was associated with increased risk of MACE.
PI0531 - ..
PI0532 - Further in the report saying...
PI0533 -
PI0534 - The risk of major cardiovascular events was 56 % higher in the
PI0535 - decreased HDL-C group compared with the unchanged HDL-C group
PI0536 - [hazard ratio (HR), 1.56; 95 % confidence interval (CI),
PI0537 - 1.122.16; p < 0.01; Table 2; Fig. 2]. The difference between
PI0538 - the two groups was due to ischaemic stroke (HR, 1.74; 95 % CI,
PI0539 - 1.003.03; p = 0.05), but was also driven by cardiovascular
PI0540 - death (HR, 1.72; 95 % CI, 0.863.42; p = 0.12).
PI0541 -
PI0542 -
PI0544 - ..
PI0545 - JACC Journal
PI0546 - Journal of the American College of Cardiology
PI0547 -
PI0548 - 2024 Mar, 83 (10) 9611026
PI0549 -
PI0550 -
PI0551 -
PI0552 -
PI0553 -
PI0554 -
PI0555 -
PI0556 -
PI0557 -
PI0558 -
PI0559 -
PI0560 -
PI0561 -
PI0562 -
PI0563 -
PI0564 -
PI0565 -
PI0566 -
PI0567 -
PI0568 -
PI06 -
SUBJECTS
Default Null Subject Account for Blank Record
PJ03 -
PJ0401 - ..
PJ0402 - Regression Arterialsclerosis Occurs with Lower LDL and Higher HDL
PJ0403 - Arterialsclerosis Regression Occurs with Lower LDL and Higher HDL
PJ0404 -
PJ0405 - Patient suffered arterial plaque buildup that required CABG x4 on
PJ0406 - 091022, ref SDS 9 PQWU, following report of chest pain while hiking
PJ0407 - hills a month earlier on 090908 1130. ref SDS 7 MY4N Arterial plaque
PJ0408 - buildup is evident in patient history of lipid panel showing low HDL <
PJ0409 - 33 at least for period 2006 - 2009, when surgery was performed,
PJ0410 - reported several months hence on 140203 1147. ref SDS 57 W25L
PJ0412 - ..
PJ0413 - Subsequent to surgery in 2009, and beginning in 2011, HDL has steadily
PJ0414 - increased to 61 in Labcorp blood test on 140201 1159. ref SDS 56 5C7M
PJ0415 - Concurrently, triglycerides have consistently dropped below 100, shown
PJ0416 - in VA lab 2 days later - TG 47 - on 140203 1147. ref SDS 57 5C7M
PJ0418 - ..
PJ0419 - While this condition seems to suggest progression of plaque buildup in
PJ0420 - arteries has ended, there is a question if existing plaque can regress
PJ0421 - to clear prior buildup?
PJ0423 - ..
PJ0424 - Research found...
PJ0425 -
PJ0426 - 19. Nature Clinical Practice
PJ0427 - Cardiovascular
PJ0428 - Medicine
PJ0430 - ..
PJ0431 - Rapid regression of atherosclerosis:
PJ0432 - insights from the clinical and experimental literature
PJ0433 -
PJ0434 - http://www.nature.com/nrcardio/journal/v5/n2/full/ncpcardio1086.html
PJ0436 - ..
PJ0437 - Nature Clinical Practice Cardiovascular Medicine (2008) 5,
PJ0438 - 91-102
PJ0439 - doi:10.1038/ncpcardio1086
PJ0440 - Received 7 March 2007 | Accepted 17 October 2007
PJ0442 - ..
PJ0443 - Kevin Jon Williams*, Jonathan E Feig and Edward A Fisher*
PJ0445 - ..
PJ0446 - About authors...
PJ0447 -
PJ0448 - http://www.nature.com/nrcardio/journal/v5/n2/authors/ncpcardio1086.html
PJ0450 - ..
PJ0451 - Email k_williams@mail.jci.tju.edu
PJ0452 -
PJ0454 - ..
PJ0455 - Atherosclerosis Commonly Considered Cannot Regress
PJ0456 -
PJ0457 -
PJ0458 - 1. The idea that human atheromata can regress at all has met
PJ0459 - considerable resistance over the decades.1, 2 Resistance to
PJ0460 - the idea of lesion regression is strengthened by the fact that
PJ0461 - advanced atheromata in humans and in animal models contain
PJ0462 - components that give an impression of permanence, such as
PJ0463 - necrosis, calcification and fibrosis. In addition, numerous
PJ0464 - theories have been proposed to explain atherogenesis that
PJ0465 - include processes thought to be difficult, if not impossible,
PJ0466 - to reverse including oxidation,3 injury,4 and cellular
PJ0467 - transformations resembling carcinogenesis.5
PJ0469 - ..
PJ0470 - 2. In this Review we summarize the failure of many established
PJ0471 - and experimental interventions to induce plaque regression,
PJ0472 - and examine other data indicating that sufficiently drastic
PJ0473 - changes in the plaque environment can stabilize and cause
PJ0474 - regression of even advanced lesions.
PJ0476 - ..
PJ0477 - CT & Intravasuclar Ultrasonography IVUS Quantify Arterial Plaque Change
PJ0478 - IVUS Intravasuclar Ultrasonography CT & Quantify Arterial Plaque Change
PJ0479 - Regression Atherosclerosis Measure Plauqe with CT and IVUS Technology
PJ0480 - Atherosclerosis Regression Measure Plauqe with CT and IVUS Technology
PJ0481 -
PJ0482 -
PJ0483 - 3. REGRESSION DOCUMENTED BY DIRECT VESSEL-WALL IMAGING
PJ0484 -
PJ0485 - Statins
PJ0487 - ..
PJ0488 - In order to track potentially more important changes in
PJ0489 - plaque composition, and to avoid the confounding effects of
PJ0490 - lesion remodeling on lumen size, arterial wall imaging is
PJ0491 - required. Recent human trials have switched from
PJ0492 - quantitative angiography, which images only the vascular
PJ0493 - lumen, to techniques that image plaque calcium (e.g.
PJ0494 - electron-beam CT) and plaque volume (e.g. intravascular
PJ0495 - ultrasonography; IVUS).
PJ0496 -
PJ0498 - ..
PJ0499 - Regression Arterialsclerosis Plaque 6.8% Rosuvastatin High Dose 18 Months
PJ0500 - Statin High Dose 18 Months Lower LDL-C < 60 and > 50% Reduce Plaque 6.8%
PJ0501 -
PJ0502 -
PJ0503 - A retrospective analysis found that aggressive
PJ0504 - LDL-cholesterol lowering with statins correlated
PJ0505 - significantly with reduction in coronary calcium-volume
PJ0506 - score by electron-beam CT, indicating that coronary artery
PJ0507 - calcifications can shrink.66 In the Reversal of
PJ0508 - Atherosclerosis with Aggressive Lipid Lowering (REVERSAL)
PJ0509 - study67 and A Study to Evaluate the Effect of Rosuvastatin
PJ0510 - on Intravascular Ultrasound-Derived Coronary Atheroma
PJ0511 - Burden (ASTEROID),68 patients with acute coronary syndromes
PJ0512 - were treated for over a year with high-dose statins and
PJ0513 - evaluated by IVUS.
PJ0515 - ..
PJ0516 - 4. The REVERSAL trial compared the high-dose statin therapy
PJ0517 - with a conventional, less-potent statin regimen. During 18
PJ0518 - months of treatment, patients treated with the conventional
PJ0519 - regimen exhibited statistically significant progression of
PJ0520 - atheroma volume (+ 2.7%), despite achieving average
PJ0521 - LDL-cholesterol levels of 2.8 mmol/l (110 mg/dl) which was
PJ0522 - close to the then-current Adult Treatment Panel III goal.69
PJ0524 - ..
PJ0525 - 5. By contrast, the high-dose statin group experienced no
PJ0526 - significant progression of atheroma volume (average
PJ0527 - LDL-cholesterol level, 2 mmol/l [79 mg/dl]). Importantly,
PJ0528 - analysis across the treatment groups found that LDL
PJ0529 - reduction exceeding approximately 50% was associated with a
PJ0530 - decrease in atheroma volume.
PJ0532 - ..
PJ0533 - 6. In ASTEROID all patients received the same high-dose
PJ0534 - therapy for 24 months and pretreatment and post-treatment
PJ0535 - IVUS findings were compared. During treatment, LDL
PJ0536 - cholesterol dropped to an average of 1.6 mmol/l (60.8
PJ0537 - mg/dl), and atheroma volume shrank by a median of 6.8%.
PJ0539 - ..
PJ0540 - 7. Hence, in both of these studies, extensive LDL-cholesterol
PJ0541 - lowering over an extended period caused established plaques
PJ0542 - to shrink.
PJ0544 - ..
PJ0545 - 8. The greater efficacy seen in ASTEROID could be explained by
PJ0546 - the lower median LDL-cholesterol level, but also by the
PJ0547 - longer treatment period and higher HDL cholesterol levels
PJ0548 - achieved in this study than in REVERSAL. As in earlier
PJ0549 - angiographic studies, we believe that these reductions in
PJ0550 - plaque volume are accompanied by favorable alterations in
PJ0551 - plaque biology, a theory which is further supported by
PJ0552 - evidence that robust plasma LDL lowering to 1.0-1.6 mmol/l
PJ0553 - or below (less than or equal to 40-60 mg/dl) is associated
PJ0554 - with further reductions in cardiovascular events.70
PJ0556 - ..
PJ0557 - This study does not report side effects taking Rosuvastatin; how many
PJ0558 - patients had to stop the statin to achieve published results.
PJ0560 - ..
PJ0561 - There is no report in this study on side effects of lowering
PJ0562 - cholesterol, per se, despite its essential role to sustain human life,
PJ0563 - reported above. ref SDS 0 VP5H and ref SDS 0 VT8L
PJ0565 - ..
PJ0566 - Cholesterol aids digestion, memory, and immunity, reported in
PJ0567 - connection with guidelines recently released by the American Heart
PJ0568 - Association AHA, shown in the record on 131112 1422. ref SDS 46 NF9H
PJ0569 -
PJ0571 - ..
PJ0572 - Rapid Regression Atherosclorotic Plaques Elevated HDL and EPCs
PJ0573 - Regression Atherosclerosis Plaque Caused By Elevation HDL and Lower LDL
PJ0574 - HDL Elevation and Lower LDL Could Cause Rapid Atherosclerosis Plaque Regression
PJ0575 - Atherosclerosis Plaque Regression Caused By HDL Elevation and Lower LDL Could
PJ0576 -
PJ0578 - ..
PJ0579 - Rapid regression atherosclerosis article continues...
PJ0580 -
PJ0581 - 9. APOB-LIPOPROTEINS AND FUNCTIONAL HDL IN ATHEROMATA
PJ0582 - REGRESSION IN HUMANS
PJ0583 -
PJ0584 - To date, human vessel-wall imaging studies suggest that
PJ0585 - intensive lowering of plasma LDL-cholesterol concentrations
PJ0586 - concomitant with elevation of functional HDL-cholesterol
PJ0587 - levels could achieve rapid plaque regression. This
PJ0588 - hypothesis is consistent with well-established
PJ0589 - epidemiology, the earlier intervention trials that show a
PJ0590 - positive correlation between clinical end points and low
PJ0591 - LDL and high HDL levels, a recent meta-analysis of IVUS
PJ0592 - trial data82 and our recent, aforementioned, experimental
PJ0593 - studies in mice. Furthermore, these strategies reduce
PJ0594 - cardiovascular events in at-risk subjects.
PJ0595 -
PJ0596 - [...below on 131125 0005 another article presents HDL
PJ0597 - and endothelium repair as driving regression of
PJ0598 - atherosclerosis. ref SDS 0 Z49G
PJ0600 - ..
PJ0601 - [...below on 131125 0005 article reports small study
PJ0602 - finding statin treatment for 12 months with Atorvastatin
PJ0603 - 80 mg combined with ezetimibe 10 mg resulted in 0.4%
PJ0604 - regression of atherosclerosis plaques. ref SDS 0 Z56P
PJ0606 - ..
PJ0607 - [On 151019 CCTA in Welch case reported complete
PJ0608 - regression of atherosclerosis after hiking 300 miles per
PJ0609 - month elevated HDL >= 60 for 12 months, and taking
PJ0610 - minimal statin regimen Atorvastatin 10 mg with Ezetimibe
PJ0611 - 10 mg yielding LDL levels > 100. ref SDS 73 SU62
PJ0613 - ..
PJ0614 - This protocol to lower LDL and increase HDL seems conflicting or at
PJ0615 - least incomplete compared with research above that arterialslerosis
PJ0616 - occurs from small, dense LDL particles that are cholesterol depleted
PJ0617 - and triglyceride rich, i.e., they are small and dense because they are
PJ0618 - cholesterol depleted, and they are cholesterol depleted because they
PJ0619 - are triglyceride rich, and they are triglyceride rich, because
PJ0620 - patients are overweight, and do not exercise enough to burn off
PJ0621 - tryglycerides. (see Doc's opinion written and edited by Axel F
PJ0622 - Sigurdsson, ref SDS 0 M95O; as well, see Doctor Attia's article.
PJ0623 - ref SDS 0 JT6K) Thus, this article might be more helpful to clarify
PJ0624 - the prescription of...
PJ0625 -
PJ0626 - ...intensive lowering of plasma LDL-cholesterol
PJ0627 - concentrations...
PJ0628 -
PJ0629 - ...to say something like...
PJ0630 -
PJ0631 - ...intensive lowering of plasma LDL-cholesterol "particle"
PJ0632 - concentrations...
PJ0633 -
PJ0634 - ...thus differentiating LDL-C from LDL-P, per Attia's article
PJ0635 - presented above. ref SDS 0 FI3G It may be that he authors intend the
PJ0636 - formulation "LDL-cholesterol concentrations" to simply state in
PJ0637 - another way "LDL particle concentrations", but that is not clear in
PJ0638 - the article.
PJ0640 - ..
PJ0641 - Rapid regression atherosclerosis article continues...
PJ0642 -
PJ0643 - 10. THE RESOLVING PLAQUE: RAPID STABILIZATION AND REGRESSION
PJ0644 -
PJ0645 - The key initiating event in atherosclerosis is the
PJ0646 - retention, or trapping, of cholesterol-rich lipoproteins
PJ0647 - within the arterial wall.15, 83, 84
PJ0649 - ..
PJ0650 - The retained lipoproteins become modified, particularly by
PJ0651 - local enzymes, and they provoke a series of responses that
PJ0652 - can account for all known features of this disease,
PJ0653 - including endothelial dysfunction and the development of
PJ0654 - the lipid-rich, vulnerable plaque.
PJ0656 - ..
PJ0657 - Recruitment of macrophages into early-stage lesions could
PJ0658 - enable phagocytosis and disposal of small quantities of
PJ0659 - retained lipoproteins. Our recent work indicates that
PJ0660 - downstream products of retained and modified lipoproteins
PJ0661 - are particularly dangerous because they eventually block
PJ0662 - the normal emigration of monocyte-derived cells (i.e.
PJ0663 - macrophages, dendritic cells) from the plaque, thereby
PJ0664 - accelerating disease progression.44, 47 These cells then
PJ0665 - become abnormally persistent within the lesion and exhibit
PJ0666 - a series of strikingly maladaptive responses that include
PJ0667 - the secretion of lipases, which greatly accelerate further
PJ0668 - lipoprotein retention and modification,85, 86 proteases,
PJ0669 - which weaken the overlying fibrous cap,87 and tissue
PJ0670 - factor, which ensures vigorous clot formation upon plaque
PJ0671 - rupture (Figure 2).88
PJ0673 - ..
PJ0674 - What causes plaque "rupture" mentioned in last sentence of this para?
PJ0675 -
PJ0676 - 11. These data imply a simple model for plaque regression
PJ0677 - (Figure 2). Major reduction in plasma apoB-lipoprotein
PJ0678 - concentrations slows further entry and retention within the
PJ0679 - arterial wall. Major enhancement of reverse lipid
PJ0680 - transport [...HDL...??] removes cellular but also
PJ0681 - extracellular lipid deposits. An early change seen
PJ0682 - following these environmental changes is restoration of
PJ0683 - normal endothelial function.18, 94, 95
PJ0685 - ..
PJ0686 - 12. We hypothesize that at some point, lipoprotein-derived
PJ0687 - lipids that had been blocking monocyte-derived cell
PJ0688 - emigration become scarce enough to enable monocytes to
PJ0689 - leave the plaque, via a process resembling dendritic cell
PJ0690 - emigration. The emigrating cells take with them their
PJ0691 - intracellular lipid, and their potential for secretion of
PJ0692 - unhelpful lipases, proteases and tissue factor.44, 45
PJ0693 - Removal of necrotic debris, calcifications and fibrosis
PJ0694 - also occurs,6, 10, 43, 66 facilitated, in theory, by new,
PJ0695 - normally functioning macrophages (i.e. they enter the
PJ0696 - regressing plaque, phagocytose and digest what they can,
PJ0697 - and donate exchangeable material to acceptor lipoproteins,
PJ0698 - but then leave).14, 96 Our study group18, 44, 45 and
PJ0699 - others30 have shown that these processes can occur
PJ0700 - surprisingly rapidly.
PJ0702 - ..
PJ0703 - 13. CONCLUSIONS AND FUTURE DIRECTIONS
PJ0704 -
PJ0705 - For regression of atheromata to become a realistic
PJ0706 - therapeutic goal, clinical practitioners must be provided
PJ0707 - with tools that extensively change plasma lipoprotein
PJ0708 - concentrations and plaque biology while avoiding adverse
PJ0709 - effects. To date, the animal and human studies that
PJ0710 - achieved clear-cut plaque regression required large
PJ0711 - reductions in plasma levels of apoB-lipoproteins, sometimes
PJ0712 - combined with brisk enhancements in reverse lipid
PJ0713 - transport. Agents to lower plasma apoB-lipoprotein
PJ0714 - concentrations include statins and cholesterol-absorption
PJ0715 - inhibitors. Although these two classes of agents have
PJ0716 - proven safe in widespread clinical use, most patients will
PJ0717 - not achieve and sustain the dramatically low
PJ0718 - LDL-cholesterol levels seen in chow-fed nonhuman
PJ0719 - primates.97 Efforts to explore other strategies that lower
PJ0720 - apoB-lipoprotein levels are underway,98, 99 but progress
PJ0721 - may be difficult because of potential adverse effects or
PJ0722 - inconvenient modes of administration. Experimental agents
PJ0723 - designed to accelerate reverse lipid transport from plaques
PJ0724 - into the liver include PC liposomes, apoA-I/PC complexes,
PJ0725 - apoA-I mimetic peptides, and two remaining CETP
PJ0726 - inhibitors.15, 100, 101 These experimental agents are
PJ0727 - either in clinical trials or preclinical testing.15, 81,
PJ0728 - 101 An extracorporeal device that delipidates HDL and
PJ0729 - returns the unloaded particles to the circulation is also
PJ0730 - undergoing testing.81 Besides the CETP inhibitors, other
PJ0731 - orally administered small molecules have been investigated
PJ0732 - preclinically for their potential to enhance
PJ0733 - HDL-cholesterol levels and reverse lipid transport, such as
PJ0734 - agonists for LXR and peroxisome proliferator-activated
PJ0735 - receptors.81
PJ0736 -
PJ0738 - ..
PJ0739 - Regression Arterialsclorosis Plaque Occurs Lower LDL-P Increased HDL
PJ0740 -
PJ0741 - This explanation seems to align with the Russert case of low LDL, but
PJ0742 - also very low HDL, i.e., statins lower LDL to target, but do not raise
PJ0743 - HDL, and likely not LDL-P, since HDL was low and triglycerides likely
PJ0744 - high due to metabolic syndrome (overweight).
PJ0746 - ..
PJ0747 - 14. On the basis of experimental data summarized above, we
PJ0748 - expect that the best regression results will be observed
PJ0749 - when plasma LDL-cholesterol concentrations are reduced and
PJ0750 - HDL function in reverse lipid transport is enhanced.
PJ0751 - Additional strategies, such as specific induction of
PJ0752 - pro-emigrant molecules to provoke the emigration of foam
PJ0753 - cells from the arterial wall, should also attract
PJ0754 - pharmaceutical interest. Rapid stabilization and
PJ0755 - regression of established plaques occurs in experimental
PJ0756 - settings in animals and humans, and we should know shortly
PJ0757 - whether plaque regression is within our grasp in the
PJ0758 - broader clinical setting as well.
PJ0760 - ..
PJ0761 - Seems like the author's expectation in 2007, when this article was
PJ0762 - published, per above, ref SDS 0 KU6J, that clinical interventions to
PJ0763 - reduce plaque buildup from arterialsclorosis would become evident
PJ0764 - "shortly," would be manifest in published studies in the past few
PJ0765 - years, now 7 years later.
PJ0766 -
PJ0767 -
PJ0768 -
PJ0769 -
PJ08 -
SUBJECTS
Default Null Subject Account for Blank Record
PK03 -
PK0401 - ..
PK0402 - Prevention Reversal Atherosclerosis Plaque
PK0403 - Regression Atherosclerosis Plaque Prevention
PK0404 - Atherosclerosis Regression Plaque Prevention
PK0405 -
PK0406 -
PK0407 - This is another article...
PK0408 -
PK0409 - 20. PMC US National Library of Medicine
PK0410 - National Institutes of Health (NIH)
PK0411 - Dovepress Vascular Health and Risk Management
PK0413 - ..
PK0414 - The prevention and regression of atherosclerotic plaques: emerging treatments
PK0415 -
PK0416 - by: Atul Ashok Kalanuria,1 Paul Nyquist,1 and Geoffrey Ling1
PK0418 - ..
PK0419 - Published online........................ 2012 September 25
PK0420 -
PK0421 - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459726/#b28-vhrm-8-549
PK0422 -
PK0423 - 1Division of Neuro Critical Care, Department of Anesthesiology
PK0424 - and Critical Care Medicine, The Johns Hopkins University
PK0425 - School of Medicine, Baltimore
PK0426 -
PK0427 - 2Department of Neurology, Uniformed Services University of the
PK0428 - Health Sciences, Bethesda, MD, USA
PK0430 - ..
PK0431 - Correspondence: Geoffrey Ling, Medical Corps, US Army,
PK0432 - Uniformed Services University of the Health Sciences, 4301
PK0433 - Jones Bridge Road, Bethesda, MD 20814, USA, Tel +1 301 295
PK0434 - 3643, Fax +1 301 295 0620, Email akalanu1@jhmi.edu
PK0436 - ..
PK0437 - 1. Abstract
PK0438 -
PK0439 - Occlusive vascular diseases, such as sudden coronary
PK0440 - syndromes, stroke, and peripheral arterial disease, are a
PK0441 - huge burden on the health care systems of developed and
PK0442 - developing countries. Tremendous advances have been made
PK0443 - over the last few decades in the diagnosis and treatment of
PK0444 - atherosclerotic diseases.
PK0446 - ..
PK0447 - Intravascular ultrasound has been able to provide detailed
PK0448 - information of plaque anatomy and has been used in several
PK0449 - studies to assess outcomes.
PK0451 - ..
PK0452 - The presence of atherosclerosis disrupts the normal
PK0453 - protective mechanism provided by the endothelium and this
PK0454 - mechanism has been implicated in the pathophysiology of
PK0455 - coronary artery disease and stroke. Efforts are being put
PK0456 - into the prevention of atherosclerosis, which has been
PK0457 - shown to begin in childhood. This paper reviews the
PK0458 - pathophysiology of atherosclerosis and discusses the
PK0459 - current options available for the prevention and reversal
PK0460 - of plaque formation.
PK0462 - ..
PK0463 - 2. Introduction.
PK0464 -
PK0465 - According to the 2012 American Heart Association (AHA)
PK0466 - statistical update, every year, approximately 795,000
PK0467 - people experience a new or recurrent stroke. Stroke
PK0468 - accounts for about one of every 18 deaths in the USA, with
PK0469 - a stroke occurring every 40 seconds, and is a major cause
PK0470 - of disability in the elderly.1 Although death rates from
PK0471 - cardiovascular diseases (CVDs) have declined, the burden of
PK0472 - disease remains high. An estimated 82.6 million American
PK0473 - adults have vascular disease, with coronary heart disease
PK0474 - (CHD) and stroke accounting for 16.3 and 7 million,
PK0475 - respectively. Mortality data show that CVD accounted for
PK0476 - 32.8% of all deaths in 2008, or one of every three deaths
PK0477 - in the USA. The total direct and indirect cost of CVD and
PK0478 - stroke in the USA for 2008 is estimated to be USD$297.7
PK0479 - billion.1 The AHA has put forth a goal to improve
PK0480 - cardiovascular health in the USA by 2020 by reducing deaths
PK0481 - from CVD and stroke by 20%. By 2030, the AHA estimates
PK0482 - that 40.5% of the US population will have some form of CVD,
PK0483 - with direct costs estimated at USD$818 billion.2 Effective
PK0484 - prevention strategies are needed if the growing burden of
PK0485 - CVD is to be arrested.
PK0487 - ..
PK0488 - 3. Brief pathophysiology of atherosclerosis.
PK0489 -
PK0490 - Atherosclerosis is a multifactorial, multistep disease that
PK0491 - involves chronic inflammation from initiation to
PK0492 - progression. All the risk factors contribute to
PK0493 - pathogenesis by aggravating the underlying inflammatory
PK0494 - process.3 Destruction of endothelium leads to loss of
PK0495 - antithrombic and fibrinolytic factors and nitrous oxide
PK0496 - (NO), an increase in the production of vasoconstrictors
PK0497 - (thromboxane A2 and prostaglandins), and an increase in
PK0498 - intracellular calcium-derived vasoconstricting factors.3
PK0499 - Endothelial damage also causes platelets to aggregate at
PK0500 - damaged sites, causing monocytes to enter the intima and
PK0501 - proliferate. Intracellular lipid peroxidation leads to
PK0502 - formation of lipoperoxides, which are toxic to plasma
PK0503 - membranes and combine with apolipoprotein (apo) B and
PK0504 - phospholipids to prevent low-density lipoprotein (LDL) from
PK0505 - binding to the LDL receptor. LDL is oxidized and acts as
PK0506 - an attractant to macrophages and monocytes. Macrophages
PK0507 - ingest LDL and become foam cells, while monocyte mobility
PK0508 - is hampered. Several other mechanisms have been implicated
PK0509 - in the formation of atheromatous plaques, including
PK0510 - imbalance between the coagulation cascade and fibrinolytic
PK0511 - systems, accumulation of free radicals, certain infections
PK0512 - and leukocytes and adhesion molecules.3 Elevated
PK0513 - homocysteine in blood leads to thrombosis, intimal
PK0514 - thickening, generation of free radicals, and alteration of
PK0515 - the methylation status of genes.3,4
PK0517 - ..
PK0518 - 4. Role of nitrous oxide NO
PK0519 -
PK0520 - Nitrous oxide and prostacyclin mediate vasodilatation of
PK0521 - the endothelium.5 Nitric oxide (NO) is synthesized from
PK0522 - the amino acid L-arginine in endothelial cells by nitric
PK0523 - oxide synthase (NOS), which maintains vascular homeostasis
PK0524 - by modulation of vascular dilator tone, regulation of
PK0525 - local cell growth, and protection of the vessel from the
PK0526 - injurious consequences of platelets and cells circulating
PK0527 - in the blood.6 Conversion of angiotensin I to angiotensin
PK0528 - II also acts as a vasoconstrictor, modulating the effect
PK0529 - of the vasododilators.5
PK0531 - ..
PK0532 - 5. Disruption of protective mechanisms
PK0533 -
PK0534 - Development of atherosclerosis leads to the disruption of
PK0535 - the mentioned protective mechanisms inherent to the
PK0536 - endothelium and causes the formation of plaque and
PK0537 - thrombosis. Coronary artery occlusion is the direct effect
PK0538 - of thrombus formation on ruptured and unruptured plaques at
PK0539 - the site of atherosclerosis and is responsible for 60%?80%
PK0540 - of acute coronary syndrome (ACS) cases.
PK0541 - Inflammation-mediated neovascularization and intra-plaque
PK0542 - hemorrhage, along with necrosis in the lipid core, are most
PK0543 - often the cause of thrombogenesis.7 Rarely, genetic
PK0544 - disorders like familial lecithin:cholesterol
PK0545 - acyltransferase deficiency and fish-eye disease cause
PK0546 - low-plasma high-density lipoprotein (HDL) and accumulation
PK0547 - of unesterified cholesterol in the body.8
PK0549 - ..
PK0550 - 6. Role of plaque formation
PK0551 -
PK0552 - Atherosclerosis with thrombus formation has been recognized
PK0553 - as a major cause of cardiovascular death. It begins early
PK0554 - in childhood and progresses in adult life when it can
PK0555 - potentially manifest as coronary artery disease (CAD),
PK0556 - stroke, and/or peripheral vascular disease. Plaque
PK0557 - formation is favored by a zone of absence of shear stress,
PK0558 - which occurs mostly, ref SDS 0 6I3K, at arterial
PK0559 - bifurcations. This is hypothesized to be related to the
PK0560 - absence of elastin at this location and the presence of
PK0561 - collagen-proteoglycan complexes, which causes LDL
PK0562 - retention.9 Plaque rupture is the most common cause of
PK0563 - arterial thrombosis coronary artery syndrome and is
PK0564 - hypothesized to be a common cause of large-vessel
PK0565 - atherosclerotic stroke. Anatomically, a ruptured plaque
PK0566 - contains a large lipid-rich core and a thin fibrous cap
PK0567 - with smooth muscles and macrophages, angiogenesis,
PK0568 - adventitial inflammation, and remodeling.10
PK0570 - ..
PK0571 - In a recent study of 697 patients, plaque morphology was
PK0572 - studied in the setting of ACS. Stone et al evaluated these
PK0573 - patients with three vessel angiograms and intravascular
PK0574 - ultrasound (IVUS) and conducted follow-up for a median of
PK0575 - 3.4 years.11 Adverse cardiac events occurred in
PK0576 - distributions of previously ?non-culprit? areas with
PK0577 - fibroatheromas or a large plaque burden.11 Increases in the
PK0578 - intimal and medial thickness of the carotid artery
PK0579 - (measured by ultrasonography) are directly associated with
PK0580 - an increased risk of myocardial infarction and stroke in
PK0581 - adults > 65 years old without a history of CVD.12
PK0582 -
PK0584 - ..
PK0585 - 7. Primary Prevention
PK0586 -
PK0587 - Since atherosclerosis begins in childhood, primary
PK0588 - prevention must begin as early as possible. To this end,
PK0589 - screening, risk-factor reduction, and appropriate use of
PK0590 - primary prevention medications are now being applied to
PK0591 - children. The 2003 AHA guidelines for primary prevention
PK0592 - of atherosclerosis beginning in childhood recommend that
PK0593 - children older than 2 years with a family history of
PK0594 - hyperlipidemia or premature cardiac disease should have
PK0595 - targeted screening of fasting lipids. Concern should be
PK0596 - raised if HDL levels are <35 mg/dL, total cholesterol is
PK0597 - borderline (> 170 mg/dL) or elevated (>200 mg/dL),
PK0598 - low-density-lipoprotein cholesterol (LDL-C) is borderline
PK0599 - (>110 mg/dL) or elevated (>130 mg/dL) or triglycerides are
PK0600 - >150 mg/dL. Screening is also recommended if family
PK0601 - history is unknown or other risk factors are present.13
PK0602 -
PK0604 - ..
PK0605 - Atherosclerosis Test Imaging Intravascular Ultrasound IVUS
PK0606 - IVUS Intravascular Ultrasound Atherosclerosis Test Imaging
PK0607 - Atherosclerosis Test Imaging Carotid Artery Intimal-Medial Thickness CIMT
PK0608 - CIMT Carotid Artery Intimal-Medial Thickness Atherosclerosis Test Imaging
PK0609 -
PK0611 - ..
PK0612 - The 2010 American College of Cardiology Foundation/AHA
PK0613 - guidelines recommend measurement of carotid artery
PK0614 - intimal-medial thickness (CIMT) for cardiovascular risk
PK0615 - assessment in asymptomatic adults at intermediate risk
PK0616 - (Class IIa recommendation, level of evidence: B).14
PK0618 - ..
PK0619 - 8. Role of screening tools
PK0620 -
PK0621 - Recently, in a National Institutes of Health-sponsored
PK0622 - multi-ethnic study conducted to validate imaging for
PK0623 - primary prevention of atherosclerosis, Zeb and Budoff
PK0624 - showed that coronary artery calcium scores and CIMT
PK0625 - evaluation are validated as a marker of atherosclerosis.16
PK0626 - Current national guidelines recommend using coronary
PK0627 - artery calcium as a screening tool for risk stratification
PK0628 - of intermediate-risk (10%-20% 10-year risk), asymptomatic
PK0629 - population (Class IIa recommendation), and low- to
PK0630 - intermediate-risk populations (6%-10% 10-year risk; level
PK0631 - of evidence: B).14,16
PK0633 - ..
PK0634 - The Screening for Heart Attack Prevention and Education
PK0635 - (SHAPE) task force conducted noninvasive screening of
PK0636 - asymptomatic men aged 45-75 years and asymptomatic women
PK0637 - aged 55-75 years. The primary goal was to detect and treat
PK0638 - all those with subclinical atherosclerosis except those
PK0639 - considered very low risk. In addition to screening for
PK0640 - risk-factor assessment (lifestyle, family history, blood
PK0641 - pressure, diabetes, hyperlipidemia, etc), the authors
PK0642 - advocate additional arterial structure testing, such as
PK0643 - carotid ultrasound, coronary calcium score by computed
PK0644 - tomography (CT) imaging, cardiac and aortic magnetic
PK0645 - resonance imaging (MRI), and ankle-brachial index.17
PK0646 - Additional arterial function testing, such as ultrasound
PK0647 - brachial vasoreactivity, as well as radial and fingertip
PK0648 - tonometry, can also be considered.
PK0650 - ..
PK0651 - In an observational study of 1118 Spanish patients over 30
PK0652 - years of age, Aguilar-Shea et al identified 320 subjects
PK0653 - as low-intermediate cardiovascular risk using the European
PK0654 - Systematic Coronary Risk Evaluation (SCORE).18 After
PK0655 - B-mode ultrasound, 18.4% of the subjects were reclassified
PK0656 - to the high-risk category, suggesting that CIMT
PK0657 - measurement could be a useful preventive tool.18
PK0659 - ..
PK0660 - An article by Hecht has further stressed the importance of
PK0661 - imaging modalities in the primary prevention of
PK0662 - atherosclerosis.19 Indeed, a focused analysis of vascular
PK0663 - anatomy often leads to the recategorizing of the risk of
PK0664 - asymptomatic individuals irrespective of their cholesterol
PK0665 - levels.
PK0667 - ..
PK0668 - 9. Role of antioxidants
PK0669 -
PK0670 - In recent years, there has been significant discussion
PK0671 - about antioxidants and their possible role in prevention of
PK0672 - atherosclerosis. The antioxidant market is a
PK0673 - multi-billion-dollar industry, but there are no randomized
PK0674 - clinical studies providing support that they are of benefit
PK0675 - in the prevention of CVD.22
PK0677 - ..
PK0678 - [...rest of this section omitted...]
PK0680 - ..
PK0681 - 10. Role of diet
PK0682 -
PK0683 - The American heart Association provides recommendations
PK0684 - for diet and lifestyle modifications (Table 1). The
PK0685 - importance of diet in cardiovascular health has been
PK0686 - summarized by Dauchet et al.25 As noted in their review,
PK0687 - most of the evidence supporting the cardio protective
PK0688 - properties of fruits and vegetables is based on
PK0689 - observational epidemiological studies, which have reported
PK0690 - either weak or associations of low significance.
PK0692 - ..
PK0693 - [...rest of this section omitted...]
PK0695 - ..
PK0696 - Exercise Vigorous 150 Minutes Moderate 75 Minutes Per Week - AHA
PK0697 -
PK0698 -
PK0699 - 11. Role of exercise
PK0700 -
PK0701 - It is now well accepted that a sedentary lifestyle
PK0702 - increases the risk of atherosclerosis. The AHA guidelines
PK0703 - recommend at least 150 minutes per week of moderate
PK0704 - exercise or 75 minutes per week of vigorous exercise or a
PK0705 - combination of moderate and vigorous activity. There are
PK0706 - several mechanisms by which exercise promotes protection
PK0707 - against atherosclerosis.
PK0709 - ..
PK0710 - Exercise reduces or prevents oxidative stress and
PK0711 - inflammation through downregulation of endothelial
PK0712 - angiotensin II type 1 receptor expression. This leads to
PK0713 - decreases in nicotinamide adenine dinucleotide
PK0714 - phosphate-oxidase activity and superoxide anion production,
PK0715 - which in turn decreases reactive oxygen species generation,
PK0716 - preservation of endothelial NO bioavailability and its
PK0717 - protective anti-atherogenic effects. This is caused by
PK0718 - endothelial activation from laminar shear stress. Skeletal
PK0719 - muscle contraction releases anti-inflammatory cytokines,
PK0720 - such as interleukin-6, which inhibits tumor necrosis
PK0721 - factor-alpha production in adipose tissue and macrophages.
PK0723 - ..
PK0724 - Weight Loss Increases HDL Lowers Blood Pressure Aided Exercise
PK0725 - Exercise Weight Loss Aids HDL Increase and Lowers Blood Pressure
PK0726 - Exercise Lowers Triglycerides LDL-P Apo B Increases HDl Decrease Plaque
PK0727 -
PK0728 -
PK0729 - Exercise-associated weight loss also leads to a lowering of
PK0730 - blood pressure, improvement in insulin sensitivity, and
PK0731 - increased HDL.27 A recent review of several observational
PK0732 - and interventional trials of the effects of physical
PK0733 - activity on CVD has found that regular exercise leads to
PK0734 - triglyceride reduction, apo B reduction, and HDL increase.
PK0735 - In addition, physical activity can also lead to an increase
PK0736 - in tissue plasminogen activator activity and a decrease in
PK0737 - coronary artery calcium.28
PK0739 - ..
PK0740 - As mentioned, risk-factor assessment is the first step in
PK0741 - the primary prevention of atherosclerotic disease. The
PK0742 - next stage of evaluation could include blood tests like
PK0743 - lipid profile as well as new markers like C-reactive
PK0744 - protein (CRP), lipoprotein-associated phospholipase A2, LDL
PK0745 - subfraction analysis, apo B/apo A-I ratio, and lipoprotein
PK0746 - A. Assessment of coronary calcification and CIMT
PK0747 - contribute to risk stratification. There is also suggestion
PK0748 - that influenza vaccine may have a preventive effect and
PK0749 - that gene therapy with genetic subtyping and proteomics may
PK0750 - lead to new preventive clinical insights.29
PK0751 -
PK0753 - ..
PK0754 - 12. Plaque regression.
PK0755 -
PK0756 - It is now known that plaques are able to regress. Plaque
PK0757 - reversal occurs by removal of lipids and necrotic material,
PK0758 - endothelial repair, or halt of vascular smooth muscle cell
PK0759 - proliferation. Several mechanisms explain this reversal,
PK0760 - such as high-density lipoprotein cholesterol (HDL-C)
PK0761 - action, destruction of foam cells and macrophages in lymph
PK0762 - nodes and restoration of endothelium by neighboring cells
PK0763 - or circulating progenitors.39
PK0765 - ..
PK0766 - This representation citing HDL combined with "circulating progenitors"
PK0767 - to restore endothelium enables regression of atherosclerotic plaques,
PK0768 - does not say lowering LDL-C, which seems to be presented in the
PK0769 - article above. ref SDS 0 6S7F
PK0770 -
PK0771 - [...below on 131125 0005 article reports small study
PK0772 - finding statin treatment for 12 months with Atorvastatin
PK0773 - 80 mg combined with ezetimibe 10 mg resulted in 0.4%
PK0774 - regression of atherosclerosis plaques. ref SDS 0 Z56P
PK0776 - ..
PK0777 - Article continues - ...regression of atherosclerotic plaques...
PK0778 -
PK0779 - 13. Role of statins, phosphodiesterase inhibitors, and
PK0780 - thiazolidinediones
PK0782 - ..
PK0783 - In a recent meta-analysis of eight trials, 919 patients
PK0784 - (461 patients in the statin group and 458 in the placebo
PK0785 - group) were studied with IVUS.40 There was no significant
PK0786 - difference between the two groups in terms of their plaque
PK0787 - characteristics at baseline. However, there was a
PK0788 - statistically significant mean difference in coronary
PK0789 - atheroma volume between the statin therapy and the placebo
PK0790 - arms, which was ?3.573 (95% CI ?4.46 to ?2.68; P < 0.01).
PK0791 - This suggests that statins have the potential to induce
PK0792 - plaque reversal.
PK0794 - ..
PK0795 - 14. One small study analyzed the effects of rosuvastatin
PK0796 - combined with ramipril on atheroma volume and its mechanism
PK0797 - in patients with intermediate CAD.41 In this study, 21
PK0798 - patients received rosuvastatin (20 mg daily) and 19
PK0799 - patients received rosuvastatin along with ramipril (20 mg
PK0800 - and 10 mg, respectively) for 9 to 12 months. The study
PK0801 - focused on measurement of TAV per 10 mm segment along with
PK0802 - lipids, metabolic parameters (adiponectin, insulin
PK0803 - sensitivity), and biomarkers (high-sensitivity [hs]-CRP,
PK0804 - matrix metalloproteinase-9) at baseline and end of study.
PK0805 - There was decrease in the TAV in both groups, with
PK0806 - reduction in the CRP levels in the combination treatment
PK0807 - group.
PK0809 - ..
PK0810 - 15. Takayama and colleagues studied the effect of rosuvastatin
PK0811 - on plaque volume on 126 patients with stable CAD on
PK0812 - lipid-lowering therapy at 37 centers in a 76-week
PK0813 - open-label study.42 Subjects received rosuvastatin 2.5 mg
PK0814 - per day (with the potential to be increased at 4-week
PK0815 - intervals to up to 20 mg per day). The primary end point
PK0816 - of percent change of plaque volume, as evaluated by IVUS
PK0817 - was ?5.1% ± 14.1% in the rosuvastatin group (P < 0.0001).
PK0819 - ..
PK0820 - 16. Hibi et al studied effects of statin treatment on plaque
PK0821 - regression in patients with polyvascular disease versus
PK0822 - those with CAD alone.43 They studied 252 patients (at 33
PK0823 - centers) with a history of an ACS, who underwent
PK0824 - percutaneous intervention to localize the lesion followed
PK0825 - by treatment with atorvastatin (20 mg per day) or
PK0826 - pitavastatin (4 mg per day). Both groups showed regression
PK0827 - of plaques, as assessed by IVUS at baseline and at 8?12
PK0828 - months follow-up. A sub-analysis of this study showed that
PK0829 - aggressive lipid lowering by pitavastatin and atorvastatin
PK0830 - results in marked regression of atherosclerotic coronary
PK0831 - lesions after ACS. The study involved data from 251
PK0832 - patients (73 were diabetic) and the authors studied the
PK0833 - association of lipid levels after statin therapy with
PK0834 - regression of atherosclerotic coronary lesions and major
PK0835 - cardiovascular events in patients after ACS. The results
PK0836 - showed that decrease in LDL-C, non-HDL-C, LDL-C/HDL-C
PK0837 - ratio, and apo B levels were all associated with a
PK0838 - progressively smaller plaque burden. In diabetic patients,
PK0839 - further reduction of these parameters was associated with a
PK0840 - significantly greater reduction in plaque volume.44
PK0842 - ..
PK0843 - 17. In a prospective randomized comparative study using
PK0844 - rosuvastatin 20 mg (n = 65) and atorvastatin 40 mg (n =
PK0845 - 63), IVUS was used at baseline and at 11-month follow-up,
PK0846 - to show effective plaque regression. TAV and percent
PK0847 - atheroma volume (PAV) was measured. Plaque was decreased in
PK0848 - 99 of 128 patients (77%; 85% [55/65] in the rosuvastatin
PK0849 - group vs 70% [44/63] in the atorvastatin group). Both
PK0850 - groups showed change in TAV: ?4.4 ± 7.3 mm3 for the
PK0851 - rosuvastatin group and ? 3.68 ± 6.8 mm3 for the
PK0852 - atorvastatin group (P = 0.5). The difference in PAV between
PK0853 - the two groups was not statistically significant (P =
PK0854 - 0.14). These results demonstrate that both statins are
PK0855 - effective in reducing plaque burden.45
PK0857 - ..
PK0858 - 18. Tani et al studied the effect of pravastatin on
PK0859 - atherosclerotic plaque in a 6-month prospective study of 64
PK0860 - patients. Pravastatin reduced plaque volume, as measured by
PK0861 - volumetric intravascular ultrasonography, by 12.6% (P <
PK0862 - 0.0001 vs baseline).46 The authors also found a significant
PK0863 - reduction in the apoB/apoA-1 ratio (P < 0.0001 vs
PK0864 - baseline).
PK0866 - ..
PK0867 - 19. The effect of atorvastatin on MRI changes in
PK0868 - atherosclerotic plaques in the thoracic and abdominal aorta
PK0869 - was studied in a prospective study in which 87 patients
PK0870 - with hypercholesterolemia were administered either
PK0871 - atorvastatin (n = 42) or atorvastatin plus etidronate (n =
PK0872 - 47) for 12 months.47 LDL levels and wall thickness in the
PK0873 - thoracic aorta were reduced in both groups (?15% and ?14%
PK0874 - for the combination therapy and monotherapy group,
PK0875 - respectively; P < 0.001 vs baseline for both groups).
PK0876 - However, only patients in the combination group had a
PK0877 - reduction in wall thickness of the abdominal aorta (?14%; P
PK0878 - < 0.001 vs baseline).
PK0880 - ..
PK0881 - 20. The SECURE study was an ongoing Phase IV double-blind
PK0882 - randomized controlled multicenter clinical trial of
PK0883 - patients who were given either a combination of cilostazol
PK0884 - and probucol or cilostazol alone.48 Plaque volume and
PK0885 - composition using IVUS was studied as the primary end point
PK0886 - at baseline and 9-month follow-up. This study has been
PK0887 - completed and results are awaited.
PK0888 -
PK0890 - ..
PK0891 - Atorvastatin 80 Ezetimibe 10 Yield Atherosclerosis Regression 0.4%
PK0892 -
PK0893 -
PK0894 - 21. Kovarnik et al randomized 89 patients to receive either
PK0895 - atorvastatin 80 mg plus ezetimibe 10 mg or standard
PK0896 - treatment per the patients' general practitioner for 12
PK0897 - months.49 The authors found a decrease in the coronary
PK0898 - artery PAV (-0.4%) in the group on combination treatment
PK0899 - versus an increase (+ 1.4%) in the other group (P = 0.014),
PK0900 - as measured by IVUS. There was also an increased frequency
PK0901 - of combined atherosclerosis regression (increased lumen
PK0902 - volume plus decreased PAV) in patients taking both
PK0903 - medications (40.5%) compared with the group on monotherapy
PK0904 - (14.9%) (P = 0.007).
PK0906 - ..
PK0907 - Doctor Alba planning treatment trial at VA Medical Center in San
PK0908 - Francisco, combining Atorvastatin 10 mg with ezetimibe 10 mg, reported
PK0909 - on 131121. ref SDS 48 6H6K Atorvastatin 10 mg is well below 80 mg
PK0910 - dose prescribed for the study that seems to report 0.4% regression of
PK0911 - atherosclerosis plaques over 1 year, thus indicating regression in
PK0912 - this case would not be related to drug treatments.
PK0913 -
PK0914 - [...above on 131125 0005 article HDL combined with
PK0915 - "circulating progenitors" to restore endothelium enables
PK0916 - regression of atherosclerotic plaques, ref SDS 0 Z49G,
PK0917 - does not say lowering LDL-C, which seems to be presented
PK0918 - in another article further above. ref SDS 0 6S7F
PK0920 - ..
PK0921 - Article continues - ...regression of atherosclerotic plaques...
PK0922 -
PK0923 - 22. A recent study used cardiovascular magnetic resonance (MR)
PK0924 - to study volumetric carotid plaque measurement on 26
PK0925 - subjects who had carotid plaques greater than 1.1 mm and
PK0926 - coronary or cerebrovascular atherosclerotic disease (mean
PK0927 - age 67 ± 2 years, 7 females).50 The subjects underwent
PK0928 - evaluation with 3 Tesla MR (T1, T2, proton density, and
PK0929 - time of flight sequences) and two-dimensional ultrasound at
PK0930 - baseline and after 6 months of statin therapy. Plaque
PK0931 - volume as measured by MR decreased by 5.8% ± 2% (1036 ± 59
PK0932 - to 976 ± 65 mm3; P = 0.018) while mean plaque volume, as
PK0933 - measured by ultrasound, was unchanged (1.12 ± 0.06 vs 1.14
PK0934 - ± 0.06 mm; P = not significant). Those patients (n = 13)
PK0935 - who had an initiation or increase of statins had ?8.8% ±
PK0936 - 2.8% change (P = 0.001), as compared with an insignificant
PK0937 - change in patients (n = 13) who were on statin maintenance.
PK0939 - ..
PK0940 - 23. Nicholls et al compared serial intravascular
PK0941 - ultrasonography in 1039 patients with coronary disease, at
PK0942 - baseline and after 104 weeks of treatment with either
PK0943 - atorvastatin, 80 mg daily, or rosuvastatin 40 mg daily.51
PK0944 - In the atorvastatin group, the atheroma volume decreased by
PK0945 - 0.99% (95% CI ?1.19 to ?0.63) and 1.22% (95% CI -1.52 to
PK0946 - -0.90) in rosuvastatin group (P = 0.17). The normalized TAV
PK0947 - was -6.39 mm3 (95% CI, -7.52 to -5.12) with rosuvastatin
PK0948 - and -4.42 mm3 (95% CI, -5.98 to -3.26) with atorvastatin (P
PK0949 - = 0.01). The side-effect profiles were acceptable in both
PK0950 - groups.
PK0952 - ..
PK0953 - 24. A previous review of four prospective randomized trials
PK0954 - showed significant regression in coronary atherosclerosis
PK0955 - associated with the lowering of LDL-C levels and an
PK0956 - increase in HDL.52 This post-hoc analysis included 1455
PK0957 - patients with angiographic CAD who underwent serial
PK0958 - intravascular ultrasonography while receiving statin
PK0959 - treatment for 18 to 24 months.
PK0961 - ..
PK0962 - 25. In their 6-month study, Yang and colleagues studied the
PK0963 - effect of pioglitazone on coronary plaque area and plaque
PK0964 - burden in patients with impaired glucose tolerance and CAD
PK0965 - who were taking atorvastatin 20 mg daily for 3 months,
PK0966 - followed by 10 mg daily for the next 3 months.53 At the
PK0967 - completion of treatment, they underwent IVUS. Compared with
PK0968 - the control group, 6 months' treatment with pioglitazone
PK0969 - significantly decreased coronary plaque burden (50.7 ± 11.1
PK0970 - vs 64.1% ± 10.3%; P < 0.05), decreased plaque area (6.22 ±
PK0971 - 2.03 vs 8.31 ± 4.29; P < 0.05), decreased thin-cap
PK0972 - fibroatheroma prevalence (11% vs 22%; P < 0.05), and
PK0973 - decreased percentage of necrotic core area (16% ± 8% vs 31%
PK0974 - ± 7%; P < 0.05). Incidentally, the patients taking
PK0975 - pioglitazone had significantly lower hs-CRP and
PK0976 - endothelin-1 levels and higher adiponectin levels.
PK0978 - ..
PK0979 - 26. Another study of 26 patients evaluated the effect of
PK0980 - pioglitazone on coronary plaque structure. IVUS was used to
PK0981 - demonstrate that pioglitazone reduced plaque burden without
PK0982 - LDL-C reduction in patients suffering from diabetes and
PK0983 - impaired glucose tolerance.54 Thirteen patients received
PK0984 - pioglitazone 15 mg per day for an initial 14 days after
PK0985 - percutaneous coronary intervention followed by 30 mg per
PK0986 - day with the remaining patients as control. At the end of 6
PK0987 - months, the pioglitazone group had significantly reduced
PK0988 - plaque volume (101.3 ± 32.1 to 94.6 ± 33.6 mm3, ?7.2%; P =
PK0989 - 0.0023). Serum cholesterol levels were also significantly
PK0990 - improved in the pioglitazone group; they had lower
PK0991 - triglyceride and CRP levels and higher HDL levels at the
PK0992 - end of the study.
PK0993 -
PK0994 -
PK0995 -
PK0996 -
PK0997 -
PK0998 -
PK10 -
SUBJECTS
Default Null Subject Account for Blank Record
PL03 -
PL0401 - ..
PL0402 - Triglycerides Lower Endurance Exercise Increase HDL
PL0403 - Endurance Exercise Increase HDL Lowers Triglycerides
PL0404 - Exercise HDL Increase Triglyceride Lower Endurance Training
PL0405 - HDL Increase Endurance Exercise Lowers Triglycerides
PL0406 -
PL0407 -
PL0408 - Another article says...
PL0409 -
PL0410 - American Heart Association
PL0412 - ..
PL0413 - Arteriosclerosis, Thrombosis, and Vascular Biology
PL0415 - ..
PL0416 - Atherosclerosis and Lipoproteins
PL0418 - ..
PL0419 - 21. Effects of Endurance Exercise Training on Plasma HDL
PL0420 - Cholesterol Levels Depend on Levels of Triglycerides
PL0422 - ..
PL0423 - Received January 29, 2001.
PL0424 - Accepted April 6, 2001.
PL0425 -
PL0426 - http://atvb.ahajournals.org/content/21/7/1226.full
PL0428 - ..
PL0429 - Evidence From Men of the Health, Risk Factors, Exercise
PL0430 - Training and Genetics (HERITAGE) Family Study
PL0432 - ..
PL0433 - Charles Couillard, Jean-Pierre Despr's, Beno't Lamarche,
PL0434 - Jean Bergeron, Jacques Gagnon, Arthur S. Leon, DC Rao,
PL0435 - James S Skinner, Jack H Wilmore, Claude Bouchard
PL0436 -
PL0437 - From the Lipid Research Center (C.C., J.-P.D., B.L., J.B.)
PL0438 - and the Laboratory of Molecular Endocrinology (J.G.),
PL0439 - Laval University Medical Research Center, CHUL Pavilion,
PL0440 - Sainte-Foy, Québec, Canada; the Physical Activity Sciences
PL0441 - Laboratory (J.G.), Department of Kinesiology, and the
PL0442 - Department of Food Sciences and Nutrition (J.-P.D., B.L.),
PL0443 - Laval University, Sainte-Foy, Québec, Canada; the Québec
PL0444 - Heart Institute (J.-P.D.), Laval Hospital Research Center,
PL0445 - Sainte-Foy, Québec, Canada; the School of Kinesiology and
PL0446 - Leisure Studies (A.S.L.), University of Minnesota,
PL0447 - Minneapolis; the Division of Biostatistics (D.C.R.),
PL0448 - Washington University Medical School, St. Louis, Mo; the
PL0449 - Department of Kinesiology (J.S.S.), Indiana University,
PL0450 - Bloomington; the Department of Health and Kinesiology
PL0451 - (J.H.W.), Texas A&M University, College Station; and the
PL0452 - Pennington Biomedical Research Center (C.B.), Louisiana
PL0453 - State University, Baton Rouge.
PL0455 - ..
PL0456 - Correspondence to Jean-Pierre Despr's, PhD, Quebec Heart
PL0457 - Institute, Pavilion Mallet, 2nd Floor, 2725 chemin Sainte-Foy,
PL0458 - Sainte-Foy, Quebec, Canada G1V 4G5. E-mail
PL0459 - Jean-Pierre.Despres@crchul.ulaval.ca
PL0461 - ..
PL0462 - 1. Abstract
PL0463 -
PL0464 - High density lipoprotein (HDL) cholesterol concentrations
PL0465 - have been shown to increase with regular endurance exercise
PL0466 - and, therefore, can contribute to a lower risk of coronary
PL0467 - heart disease in physically active individuals compared
PL0468 - with sedentary subjects.
PL0470 - ..
PL0471 - Hypoalphalipoproteinemia - Low HDL < 35
PL0472 -
PL0473 -
PL0474 - 2. Although low HDL cholesterol levels are frequently observed
PL0475 - in combination with hypertriglyceridemia [...triglycerides
PL0476 - elevated above 150...], some individuals may be
PL0477 - characterized by isolated hypoalphalipoproteinemia, ie, low
PL0478 - HDL cholesterol levels in the absence of elevated
PL0479 - triglyceride (TG) concentrations.
PL0481 - ..
PL0482 - Low HDL and low triglycerides seems evident in patient history for
PL0483 - lipid profile the past 9 years, reported on 140203 1147. ref SDS 57
PL0484 - W25L
PL0486 - ..
PL0487 - AHA Article Published January 29, 2001 continues...
PL0488 -
PL0489 - 3. The present study compared the responses of numerous
PL0490 - lipoprotein-lipid variables to a 20-week endurance exercise
PL0491 - training program in men categorized on the basis of
PL0492 - baseline TG and HDL cholesterol concentrations: (1) low TG
PL0493 - and high HDL cholesterol (normolipidemia), (2) low TG and
PL0494 - low HDL cholesterol (isolated low HDL cholesterol), (3)
PL0495 - high TG and high HDL cholesterol (isolated high TGs), and
PL0496 - (4) high TGs and low HDL cholesterol (high TG/low HDL
PL0497 - cholesterol).
PL0499 - ..
PL0500 - 4. A series of physical and metabolic variables was measured
PL0501 - before and after the training program in a sample of 200
PL0502 - men enrolled in the Health, Risk Factors, Exercise Training
PL0503 - and Genetics (HERITAGE) Family Study.
PL0505 - ..
PL0506 - 5. At baseline, men with high TG/low HDL cholesterol had more
PL0507 - visceral adipose tissue than did men with isolated low HDL
PL0508 - cholesterol and men with normolipidemia. The 0.4% (not
PL0509 - significant) exercise-induced increase in HDL cholesterol
PL0510 - levels in men with isolated low HDL cholesterol suggests
PL0511 - that they did not benefit from the "HDL-raising" effect of
PL0512 - exercise.
PL0514 - ..
PL0515 - 6. In contrast, men with high TG/low HDL cholesterol showed a
PL0516 - significant increase in HDL cholesterol levels (4.9%,
PL0517 - P<0.005). Whereas both subgroups of men with elevated TG
PL0518 - levels showed reductions in plasma TGs (??15.0%, P<0.005),
PL0519 - only those with high TG/low HDL cholesterol showed
PL0520 - significantly reduced apolipoprotein B levels at the end of
PL0521 - the study (?6.0%, P<0.005).
PL0523 - ..
PL0524 - 7. Multiple regression analyses revealed that the
PL0525 - exercise-induced change in abdominal subcutaneous adipose
PL0526 - tissue [... fat ...] (10.6%, P<0.01) was the only
PL0527 - significant correlate of the increase in plasma HDL
PL0528 - cholesterol with training in men with high TG/low HDL
PL0529 - cholesterol. Results of the present study suggest that
PL0530 - regular endurance exercise training may be particularly
PL0531 - helpful in men with low HDL cholesterol, elevated TGs, and
PL0532 - abdominal obesity.
PL0534 - ..
PL0535 - 8. Endurance Exercise Training Program
PL0536 -
PL0537 - Participants trained under supervision in the clinical
PL0538 - centers on a cycle ergometer (Universal Aerobicycle) for 60
PL0539 - sessions by using the same standardized training protocol.
PL0540 - They were required to complete the 60 sessions within 21
PL0541 - weeks. They could not exercise >1 session per day, >4
PL0542 - sessions per week, or <1 session per week.
PL0544 - ..
PL0545 - This study tested patients for endurance exercise using a stationary
PL0546 - bicycle - Universal Aerobicycld...
PL0547 -
PL0548 - http://www.shopwiki.com/l/universal-aerobicycle-upright-stationary-exercise-bikes
PL0550 - ..
PL0551 - AHA Article Published January 29, 2001 continues...
PL0552 -
PL0553 - 9. Training sessions during the first 2 weeks began at an HR
PL0554 - associated with 55% VO2max for 30 minutes. Either duration
PL0555 - or intensity was then increased each 2 weeks until the
PL0556 - 14th week of training, when participants exercised at the
PL0557 - HR associated with 75% of their initial VO2max for 50
PL0558 - minutes. This was then maintained for the next 6 weeks.
PL0560 - ..
PL0561 - Training 3 - 4 days per week for 50 minutes does not seem like
PL0562 - "endurance" training.
PL0564 - ..
PL0565 - The critical factor is level of effort. Longer distances and higher
PL0566 - speeds for longer periods increases results at low initial levels.
PL0568 - ..
PL0569 - How would this compare to hiking 5 - 7 days per week for 180 - 360
PL0570 - minutes per session?
PL0571 -
PL0573 - ..
PL0574 - HDL Low Biggest Risk CVD CAD Heart Attack
PL0575 - VA HDL Intervention Study Found HDL Strongest Protection Against CVD
PL0576 -
PL0577 -
PL0578 - 10. It is well established that low plasma HDL cholesterol
PL0579 - levels are associated with an increased risk of CHD.33 34
PL0580 - Indeed, a low HDL cholesterol concentration has been shown
PL0581 - to be the most prevalent abnormality of the
PL0582 - lipoprotein-lipid profile reported among men with
PL0583 - documented CHD.35 In this regard, the recently published
PL0584 - results of the Veterans Affairs High-Density Lipoprotein
PL0585 - Intervention Trail (VA-HIT) Study36 clearly show that
PL0586 - pharmacotherapy aimed at increasing plasma HDL cholesterol
PL0587 - levels reduces the risk of CHD, even in the absence of any
PL0588 - change in plasma LDL cholesterol levels; this latter
PL0589 - finding is commonly observed when CHD patients with low HDL
PL0590 - cholesterol levels are treated with a fibrate such as
PL0591 - gemfibrozil.
PL0593 - ..
PL0594 - This finding aligns with patient profile history showing relatively
PL0595 - low triglycerides, but also low HDL with LDL not excessively elevated.
PL0596 - 140203 1147, ref SDS 57 W25L
PL0598 - ..
PL0599 - The factor in this case seems to be weight control. For most of the
PL0600 - time from 2006 until CABG +4 surgery on 091022, patient weighed
PL0601 - 200-210. On or about August/July 2009 patient suddenly lost about 30
PL0602 - pounds over a period of 2 months, due to accumulated effects of
PL0603 - achalasia (swallowing problems).
PL0605 - ..
PL0606 - AHA Article Published January 29, 2001 continues...
PL0607 -
PL0608 - 11. It is now fairly well recognized that endurance exercise
PL0609 - training can increase plasma HDL cholesterol levels1 2 3
PL0610 - if the exercise training stimulus is sufficient.
PL0612 - ..
PL0613 - 12. Furthermore, several studies have suggested that the
PL0614 - HDL-raising effect of endurance exercise training could be
PL0615 - largely explained by the concomitant loss of body mass or
PL0616 - fat.37
PL0618 - ..
PL0619 - 13. Therefore, among high-risk overweight dyslipidemic patients
PL0620 - with insulin resistance, hyperinsulinemia,
PL0621 - hypertriglyceridemia, and low HDL cholesterol levels, the
PL0622 - net increase in the daily energy expenditure produced by
PL0623 - regular endurance exercise may eventually induce
PL0624 - mobilization of body fat and weight loss. In turn, this
PL0625 - may ultimately reduce the amount of abdominal fat, improve
PL0626 - insulin action, lower TG levels, and increase plasma HDL
PL0627 - cholesterol concentrations.38 These favorable metabolic
PL0628 - improvements explain why regular endurance exercise of
PL0629 - moderate intensity but of long duration is advocated for
PL0630 - the management of obesity and of its related high TG/low
PL0631 - HDL cholesterol dyslipidemia.
PL0633 - ..
PL0634 - Exercise protocol for reducing weight, lowering triglycerides, and
PL0635 - raising HDL is low intensity for long duration.
PL0637 - ..
PL0638 - Hiking 3 - 4 hours (11 - 25 miles) per day for 7 days meets this
PL0639 - criteria.
PL0641 - ..
PL0642 - AHA Article Published January 29, 2001 continues...
PL0643 -
PL0644 - 14. However, low plasma HDL cholesterol is a heterogeneous
PL0645 - condition.
PL0647 - ..
PL0648 - Apart from rare monogenic disorders,39 40 41 it is not
PL0649 - uncommon to find individuals with low HDL cholesterol
PL0650 - levels in the absence of abdominal obesity, insulin
PL0651 - resistance, or hypertriglyceridemia. For instance, in the
PL0652 - present study, 38 men of the total sample of 200 men (19%
PL0653 - of the sample) had plasma HDL cholesterol levels <0.92
PL0654 - mmol/L, while simultaneously having plasma TG levels <1.34
PL0655 - mmol/L. This group with isolated low HDL cholesterol had
PL0656 - very low average plasma cholesterol as well as LDL
PL0657 - cholesterol, apoB, and apoA-I levels. Furthermore, they
PL0658 - were not obese and did not differ from normolipidemic
PL0659 - subjects for abdominal fat accumulation. It also seems
PL0660 - important to point out that men with isolated low HDL
PL0661 - cholesterol had a VO2max at baseline as high as that of
PL0662 - normolipidemic men, suggesting that they were as physically
PL0663 - fit as normolipidemic men. These results are consistent
PL0664 - with our previously published study in which we reported
PL0665 - that patients with isolated hypoalphalipoproteinemia were
PL0666 - not characterized by abdominal obesity or by the features
PL0667 - of insulin resistance.12 Because these patients were
PL0668 - neither overweight nor hyperinsulinemic, we hypothesized
PL0669 - that they might show a specific response pattern to a
PL0670 - standardized endurance exercise training program.
PL0672 - ..
PL0673 - 15. Indeed, men with high TG/low HDL cholesterol displayed the
PL0674 - expected favorable changes in the lipoprotein profile in
PL0675 - response to the standardized exercise training program (eg,
PL0676 - decrease in plasma TG, cholesterol, LDL cholesterol, and
PL0677 - apoB levels and an increase in apoA-I and HDL cholesterol).
PL0678 - Furthermore, the concomitant increases in HDL2 cholesterol
PL0679 - and apoA-I in men with high TG/low HDL cholesterol suggest
PL0680 - simultaneous effects of exercise training on the density
PL0681 - and number of HDL particles.
PL0683 - ..
PL0684 - 16. On the other hand, exercise training was unsuccessful in
PL0685 - raising plasma HDL cholesterol levels in subjects with
PL0686 - isolated low HDL cholesterol. The lack of response in
PL0687 - subjects with isolated low HDL cholesterol could not be
PL0688 - attributed to differences in the compliance to the training
PL0689 - program or to difference in cardiorespiratory adaptations,
PL0690 - inasmuch as the absolute and relative increase in VO2max
PL0691 - was similar among all study groups. Furthermore, all
PL0692 - groups displayed similar favorable changes in the
PL0693 - PH-HL/PH-LPL ratio, which we have previously shown to be a
PL0694 - significant correlate of plasma HDL cholesterol levels.28
PL0696 - ..
PL0697 - 17. However, Williams et al/43 also reported a significant and
PL0698 - positive association between baseline HDL cholesterol
PL0699 - levels and the subjects' running mileage during the trial,
PL0700 - which led them to suggest that greater distances and a more
PL0701 - important weight loss may have accounted, at least in part,
PL0702 - for the larger increase in HDL cholesterol levels in these
PL0703 - individuals.
PL0705 - ..
PL0706 - This is the main issue on raising HDL - longer distance and weight
PL0707 - loss, which means in part diet control and hiking faster, i.e.,
PL0708 - causing the body to reach an energy "burn-rate" sufficient to trigger
PL0709 - release of reserves, commonly called "fat."
PL0711 - ..
PL0712 - It would seem this requires subjecting the body to conditions from
PL0713 - which human biology evolved that required a lot of effort to obtain
PL0714 - life-sustaining, scarce food supply, while moving fast enough to avoid
PL0715 - becoming food supply for others. (see next article, ref SDS 0 E265).
PL0717 - ..
PL0718 - This premis reported in 2001, of raising HDL by hiking faster
PL0719 - conflicts with later research that hiking longer raises HDL higher
PL0720 - than hiking faster, per article above. ref SDS 0 VO5I
PL0721 -
PL0722 -
PL0723 -
PL0724 -
PL0725 -
PL08 -
SUBJECTS
CoQ10 Recover Statins Side Effects Muscle Myopathy Energy Boost Rese
PN03 -
PN0401 - ..
PN0402 - HDL Increased with Ubiquinol CoQ10
PN0403 - CoQ10 HDL Increased with Ubiquinol
PN0404 - Ubiquinol HDL Increased with CoQ10
PN0405 -
PN0406 -
PN0407 - NIH
PN0408 - National Library of Medicine
PN0409 - PubMed
PN0411 - ..
PN0412 - Effects of Coenzyme Q10 Supplementation on Lipid Profiles in
PN0413 - Adults: A Meta-analysis of Randomized Controlled Trials
PN0414 -
PN0415 -
PN0416 - https://pubmed.ncbi.nlm.nih.gov/36337001/
PN0417 -
PN0418 - 2022 Dec 17;108(1):232-249.
PN0420 - ..
PN0421 - PMID: 36337001 DOI: 10.1210/clinem/dgac585
PN0422 -
PN0424 - ..
PN0425 - Abstract
PN0427 - ..
PN0428 - Context: Previous meta-analyses have suggested that the
PN0429 - effects of coenzyme Q10 (CoQ10) on lipid profiles remain
PN0430 - debatable. Additionally, no meta-analysis has explored the
PN0431 - optimal intake of CoQ10 for attenuating lipid profiles in
PN0432 - adults.
PN0434 - ..
PN0435 - Objective: This study conducted a meta-analysis to determine
PN0436 - the effects of CoQ10 on lipid profiles and assess their
PN0437 - dose-response relationships in adults.
PN0439 - ..
PN0440 - Methods: Databases (Web of Science, PubMed/Medline, Embase,
PN0441 - and the Cochrane Library) were systematically searched until
PN0442 - August 10, 2022. The random effects model was used to
PN0443 - calculate the mean differences (MDs) and 95% CI for changes in
PN0444 - circulating lipid profiles. The novel single-stage restricted
PN0445 - cubic spline regression model was applied to explore nonlinear
PN0446 - dose-response relationships.
PN0448 - ..
PN0449 - Results: Fifty randomized controlled trials with a total of
PN0450 - 2794 participants were included in the qualitative synthesis.
PN0451 - The pooled analysis revealed that CoQ10 supplementation
PN0452 - significantly reduced total cholesterol (TC) (MD -5.53 mg/dL;
PN0453 - 95% CI -8.40, -2.66; I2 = 70%), low-density lipoprotein
PN0454 - cholesterol (LDL-C) (MD -3.03 mg/dL; 95% CI -5.25, -0.81; I2 =
PN0455 - 54%), and triglycerides (TGs) (MD -9.06 mg/dL; 95% CI -14.04,
PN0456 - -4.08; I2 = 65%) and increased high-density lipoprotein
PN0457 - cholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 =
PN0458 - 82%). The dose-response analysis showed an inverse J-shaped
PN0459 - nonlinear pattern between CoQ10 supplementation and TC in
PN0460 - which 400-500 mg/day CoQ10 largely reduced TC (?2 = 48.54, P <
PN0461 - .01).
PN0463 - ..
PN0464 - Conclusion: CoQ10 supplementation decreased the TC, LDL-C, and
PN0465 - TG levels, and increased HDL-C levels in adults, and the
PN0466 - dosage of 400 to 500 mg/day achieved the greatest effect on
PN0467 - TC.
PN0469 - ..
PN0470 - Keywords: CoQ10 supplementation; dyslipidemia; lipid profiles;
PN0471 - meta-analysis.
PN0472 -
PN0473 - © The Author(s) 2022. Published by Oxford University Press on
PN0474 - behalf of the Endocrine Society. All rights reserved. For
PN0475 - permissions, please e-mail: journals.permissions@oup.com.
PN0476 -
PN0478 - ..
PN0479 - This article does not indicate over what period of time results
PN0480 - occur.
PN0481 -
PN0482 -
PN0484 - ..
PN0485 - Another study found no effect on HDL after taking CoQ10 for 3 months.
PN0487 - ..
PN0488 - Co-enzyme Q10 supplementation for the primary prevention of
PN0489 - cardiovascular disease
PN0490 - -----------------------------------------------------------
PN0491 -
PN0492 - https://pubmed.ncbi.nlm.nih.gov/25474484/
PN0494 - ..
PN0495 - Main results: (last sentence says...)
PN0496 - In contrast, there was no significant difference in the change
PN0497 - in HDL-cholesterol and triglycerides after three months
PN0498 - between the four arms of the trial.
PN0499 -
PN0500 -
PN0501 -
PN0502 -
PN06 -
SUBJECTS
Magnesium Depleted During Long Hikes Requires Continual Infusion Thr
PP03 -
PP0401 - ..
PP0402 - Magnesium Malate Increases Energy Avoid Fatigue During Long Hikes
PP0403 - Energy Magnesium Malate Increases Avoid Fatigue During Long Hikes
PP0404 - Fatigue Avoid During Long Hikes Magnesium Malate Increases Energy
PP0405 -
PP0406 - Long hikes to raise HDL and EPCs depletes magnesium, which is needed
PP0407 - for energy to continue hiking.
PP0409 - ..
PP0410 - Have had many blood tests, but only test at VAMCSF on 191030 reported
PP0411 - in electrolyte metabolic panel magnesium 2.3 for range 1.6 - 2.7, (see
PP0412 - bottom of list). ref SDS 80 ZG5O That day at VAMCSF, hiked 12 miles
PP0413 - through Golden Gate Park and back. Four (4) years later in 2023,
PP0414 - hiking 20 +/- miles, so there may be more depletion of magnesium.
PP0415 -
PP0417 - ..
PP0418 - In 2023 Kathy needed multiple magnesium injections at the hospital ER,
PP0419 - because her chemotherapy depleted magnesium, and she became very weak
PP0420 - to even walk around the house, e.g., could not stand up from a chair.
PP0421 -
PP0422 -
PP0423 - Natonal Library of Medicine
PP0425 - ..
PP0426 - Can Magnesium Enhance Exercise Performance?
PP0427 -
PP0428 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622706/
PP0430 - ..
PP0431 - Published online 2017 Aug 28. doi: 10.3390/nu9090946
PP0432 - PMCID: PMC5622706
PP0433 - PMID: 28846654
PP0435 - ..
PP0436 - Abstract
PP0437 - Magnesium (Mg) is an essential mineral that plays a critical
PP0438 - role in the human body. It takes part in the process of energy
PP0439 - metabolism and assists the maintenance of normal muscle
PP0440 - function. A number of studies evaluated the association
PP0441 - between Mg status/supplementation and exercise performance and
PP0442 - found that the need for Mg increased as individuals? physical
PP0443 - activity level went up. Animal studies indicated that Mg might
PP0444 - improve exercise performance via enhancing glucose availability
PP0445 - in the brain, muscle and blood; and reducing/delaying lactate
PP0446 - accumulation in the muscle. The majority of human studies
PP0447 - focused on physiological effects in blood pressure, heart rate
PP0448 - and maximal oxygen uptake (VO2 max), rather than direct
PP0449 - functional performances. Some cross-sectional surveys
PP0450 - demonstrated a positive association between Mg status and
PP0451 - muscle performance, including grip strength, lower-leg power,
PP0452 - knee extension torque, ankle extension strength, maximal
PP0453 - isometric trunk flexion, rotation, and jumping performance.
PP0454 - Additionally, findings from intervention studies showed that Mg
PP0455 - supplementation might lead to improvements in functional
PP0456 - indices such as quadriceps torque. Moreover, Mg
PP0457 - supplementation could improve gait speed and chair stand time
PP0458 - in elderly women. This comprehensive review summarized the
PP0459 - literature from both animal and human studies and aimed to
PP0460 - evaluate scientific evidence on Mg status/supplementation in
PP0461 - relation to exercise performance.
PP0462 -
PP0463 -
PP0464 -
PP0466 - ..
PP0467 - Best form of magnesium for hiking is Magnesium malate"....
PP0468 -
PP0469 - Balance Womens Health
PP0470 - Types of MAGNESIUM
PP0471 -
PP0472 - https://balancewomenshealth.com/wp-content/uploads/2020/03/PE-H-Types-of-Magnesium.pdf
PP0473 -
PP0475 - ..
PP0476 - Magnesium malate -- Magnesium malate is a fantastic choice for
PP0477 - people suffering from fatigue, since malic acid -- a natural
PP0478 - fruit acid present in most cells in the body -- is a vital
PP0479 - component of enzymes that play a key role in ATP synthesis and
PP0480 - energy production. Since the ionic bonds of magnesium and
PP0481 - malic acid are easily broken, magnesium malate is also highly
PP0482 - soluble.
PP0483 -
PP0485 - ..
PP0486 - The article says magnesium is consumed through diet with peanut butter
PP0487 - (smooth) - 2 tbsp, avocado cubed - 1 cup, and 1 banana, all of which
PP0488 - are taken at approximate 6 miles stops, though at less than
PP0489 - prescribed amounts.
PP0490 -
PP0492 - ..
PP0493 - Easiest form of fast acting magnesium malate is liquid form, thinking
PP0494 - of taking it mile 18 or so. Taking Ubiquinol CoQ10 before starting
PP0495 - hikes, and again at mile 10, provides energy for doing Crystal Ranch
PP0496 - road loop. By that time/distance - 4 hours 18 miles, magnesium has
PP0497 - been depleted, so needs to be restored.
PP0499 - ..
PP0500 - Choices to restore magnesium malate and dosage
PP0501 -
PP0502 - Magnesium Malate Liquid Form
PP0503 -
PP0504 - https://www.google.ca/search?as_q=Magnesium+malate+liquid+form&as_epq=&as_oq=&as_eq=&as_nlo=&as_nhi=&lr=&cr=&as_qdr=all&as_sitesearch=&as_occt=any&as_filetype=&tbs=
PP0505 -
PP0506 - Ionic Magnesium Liquid Supplement....... taste terrible
PP0507 - Size: 8 fl oz. - 96 Servings
PP0509 - ..
PP0510 - Price..................... $21.97
PP0511 -
PP0512 -
PP0514 - ..
PP0515 - Amazon
PP0517 - ..
PP0518 - Trace Minerals Research Ionic Magnesium - 4 oz - Can Help with
PP0519 - Muscle Cramps and Muscle Fatigue - Naturally Sourced and 100%
PP0520 - Natural
PP0521 -
PP0522 - https://www.amazon.com/Trace-Minerals-Research-Ionic-Magnesium/dp/B01JHRSY18/ref=asc_df_B01JHRSY18/?tag=hyprod-20&linkCode=df0&hvadid=666664521976&hvpos=&hvnetw=g&hvrand=3537277703882967409&hvpone=&hvptwo=&hvqmt=&hvdev=c&hvdvcmdl=&hvlocint=&hvlocphy=9031996&hvtargid=pla-1390566442681&psc=1&gclid=EAIaIQobChMIhZmx4JjAgQMVRM3CBB20EgqeEAQYAyABEgJLIPD_BwE
PP0524 - ..
PP0525 - Price..................... $17.09
PP0526 -
PP0527 -
PP0528 -
PP0529 -
PP0530 -
PP0531 -
PP0532 -
PP0533 -
PP0534 -
PP06 -
SUBJECTS
Default Null Subject Account for Blank Record
PQ03 -
PQ0401 - ..
PQ0402 - Exercise Genetic Requirement Human Cardiovascular Survival
PQ0403 - Endurance Exercise Effects Cardiovascular Endothelial Function
PQ0404 - Exercise Recovery Cardiovasular Disease Endothelial Function
PQ0405 - Cardiovasular Disease Exercise Recovery Endothelial Function
PQ0406 -
PQ0408 - ..
PQ0409 - American Heart Association
PQ0411 - ..
PQ0412 - Circulation
PQ0414 - ..
PQ0415 - 22. Exercise in Cardiovascular Disease
PQ0416 - Cardiovascular Effects of Exercise Training
PQ0417 - Molecular Mechanisms
PQ0418 -
PQ0419 - http://circ.ahajournals.org/content/122/12/1221.full#sec-34
PQ0421 - ..
PQ0422 - September 21, 2010
PQ0423 - Vol 122, Issue 12
PQ0425 - ..
PQ0426 - Stephan Gielen, MD; Gerhard Schuler, MD; Volker Adams, PhD
PQ0428 - ..
PQ0429 - Correspondence to Volker Adams, PhD, Department of Internal
PQ0430 - Medicine/Cardiology, University of Leipzig, Heart Center,
PQ0431 - Strümpellstraße 39, 04289 Leipzig, Germany. E-mail
PQ0432 - adav@medizin.uni-leipzig.de
PQ0433 -
PQ0434 - 1. In the natural habitat of our ancestors, physical activity
PQ0435 - was not a preventive intervention but a matter of survival.
PQ0436 - In this hostile environment with scarce food and ubiquitous
PQ0437 - dangers, human genes were selected to optimize aerobic
PQ0438 - metabolic pathways and conserve energy for potential future
PQ0439 - famines.1 Cardiac and vascular functions were continuously
PQ0440 - challenged by intermittent bouts of high-intensity physical
PQ0441 - activity and adapted to meet the metabolic demands of the
PQ0442 - working skeletal muscle under these conditions.
PQ0444 - ..
PQ0445 - 2. The statistical average of physical activity in Western
PQ0446 - societies is so much below the levels normal for our
PQ0447 - genetic background that sedentary lifestyle in combination
PQ0448 - with excess food intake has surpassed smoking as the No. 1
PQ0449 - preventable cause of death in the United States.2
PQ0451 - ..
PQ0452 - 3. Cardiac Effects of Exercise
PQ0454 - ..
PQ0455 - This section omitted to save time, since at the moment focus of
PQ0456 - research is on regression (i.e., recovery from) atherosclerosis
PQ0457 - plaque (lesions).
PQ0458 -
PQ0459 -
PQ0460 - 4. Vascular Effects of Exercise
PQ0461 -
PQ0462 - There are several reasons why endothelial research became
PQ0463 - so significant for today's mechanistic concepts of
PQ0464 - exercise-mediated cardiovascular effects:
PQ0465 -
PQ0466 - 1. Endothelial dysfunction has been found to be a
PQ0467 - condition sine qua non for atherogenesis (ie, an obligatory
PQ0468 - initial step in early atherosclerosis).102 Thus, prevention
PQ0469 - of endothelial dysfunction will necessarily prevent
PQ0470 - atherosclerosis development.
PQ0472 - ..
PQ0473 - 2. The presence of endothelial dysfunction predicts future
PQ0474 - cardiovascular events.103,104 Hence, endothelial
PQ0475 - function measurements were proposed as a surrogate end
PQ0476 - point in clinical research.105
PQ0478 - ..
PQ0479 - 3. Endothelial function can be assessed by a large variety
PQ0480 - of methods in both animal and human studies.
PQ0481 - Surgical/invasive methods include organ bath
PQ0482 - measurements of arterial rings harvested in animals or
PQ0483 - during aortocoronary bypass surgery in humans and
PQ0484 - catheter-based assessment of acetylcholine-induced
PQ0485 - vasodilatation with angiography of the target vessel.
PQ0487 - ..
PQ0488 - Noninvasive methods such as brachial/radial ultrasound,
PQ0489 - magnetic resonance imaging, and venous occlusion
PQ0490 - plethysmography permit serial studies comparing
PQ0491 - endothelial function before and after an exercise
PQ0492 - intervention.
PQ0494 - ..
PQ0495 - These classic methodologies are increasingly
PQ0496 - supplemented by commercial semiautomatic devices using,
PQ0497 - for example, digital pulse amplitude tonometry to
PQ0498 - measure microvascular function.106
PQ0500 - ..
PQ0501 - 5. Exercise and Conduit Vessel Vasomotor Function in Coronary
PQ0502 - Artery Disease
PQ0504 - ..
PQ0505 - 6. The clinical effects of endurance exercise training on
PQ0506 - coronary endothelial function were first studied in humans
PQ0507 - by Hambrecht et al117: A 4-week endurance training program
PQ0508 - was effective in attenuating the paradoxical arterial
PQ0509 - vasoconstriction in epicardial conduit vessels by -54% and
PQ0510 - increased average peak flow velocity by +78% in response to
PQ0511 - intracoronary acetylcholine infusion. The improvements in
PQ0512 - coronary endothelial function were partially lost during a
PQ0513 - consecutive 5-month home-based endurance training program
PQ0514 - at lower intensity, and changes were related to daily
PQ0515 - training durations.118
PQ0517 - ..
PQ0518 - 7. In a subsequent study examining training effects on the
PQ0519 - peripheral conduit artery function, Gokce et al119
PQ0520 - measured brachial and femoral artery endothelial function
PQ0521 - in patients with coronary artery disease before and after
PQ0522 - a 10-week leg exercise program. They documented
PQ0523 - significant improvement in endothelium-dependent,
PQ0524 - flow-mediated dilation in conduit arteries of the leg but
PQ0525 - not the arm and hypothesized that training effects could
PQ0526 - be limited to the trained limb. This may, however, also
PQ0527 - depend on the distribution of endothelial dysfunction and
PQ0528 - the intensity of the training program because Linke et
PQ0529 - al120 were able to confirm improved radial artery
PQ0530 - endothelial function after pure bicycle ergometer training
PQ0531 - in patients with CHF.
PQ0532 -
PQ0534 - ..
PQ0535 - Exercise Signals Bone Marrow Increase EPCs Atherosclerosis Regression
PQ0536 - Atherosclerosis Regression EPCs Increase Exercise Signals Bone Marrow
PQ0537 - Regression Atherosclerosis EPCs Increase Exercise Signals Bone Marrow
PQ0538 - EPCs Produced Bone Marrow Increased Exercise Repair Endothelial Lining
PQ0539 -
PQ0540 -
PQ0541 - 8. Exercise and EPCs.
PQ0542 -
PQ0543 - The first description of postnatal vasculogenesis and the
PQ0544 - characterization of EPCs derived from adult bone marrow
PQ0545 - changed our concept of vascular plasticity in health and
PQ0546 - disease.138 In addition to EPCs, mesenchymal stem cells
PQ0547 - also possess the potential for vascular regeneration.139
PQ0548 - Both mesenchymal stem cells and EPCs are mobilized from the
PQ0549 - bone marrow in response to ischemia, exercise, and
PQ0550 - neurohormonal factors (eg, vascular endothelial growth
PQ0551 - factor [VEGF], placental growth factor) and critically
PQ0552 - contribute to maintaining the integrity of the endothelial
PQ0553 - cell layer. EPC number and function correlate with the
PQ0554 - number of cardiovascular risk factors and disease severity
PQ0555 - and predict cardiovascular events and death from
PQ0556 - cardiovascular causes.140
PQ0558 - ..
PQ0559 - It is a matter of continuing debate whether
PQ0560 - training-induced flow changes or ischemia induction is
PQ0561 - required to stimulate EPC release. In 2 clinical studies,
PQ0562 - we demonstrated that an increase in circulating EPCs was
PQ0563 - only achieved in response to exercise-induced ischemia,
PQ0564 - whereas matrigel assays indicated improved EPC function in
PQ0565 - nonischemic training, as well.141,142 Other authors showed
PQ0566 - exercise-related EPC increase also in the absence of
PQ0567 - ischemia.143,144 Prolonged strenuous exercise
PQ0568 - (half-marathon, marathon, or spartathlon), however, showed
PQ0569 - no change or a significant increase in circulating
PQ0570 - progenitor cells.145,?,148
PQ0572 - ..
PQ0573 - The principal mechanism of EPC mobilization from the bone
PQ0574 - marrow seems to depend on the activation of eNOS in the
PQ0575 - presence of several mobilizing factors such as VEGF149 or
PQ0576 - placental growth factor.150 Gene-targeting studies using
PQ0577 - either MMP-2151 or MMP-9152 knockout mice demonstrated that
PQ0578 - the presence of MMPs is crucial in ischemia-induced
PQ0579 - mobilization of EPCs and hence neovascularization.
PQ0581 - ..
PQ0582 - 9. At the molecular/cellular level, the following scenario for
PQ0583 - the mobilization is proposed (Figure 5): Under steady
PQ0584 - state conditions, progenitor cells reside in a niche of the
PQ0585 - bone marrow, bound to stroma cells via adhesion molecules
PQ0586 - such as vascular cell adhesion molecule/very late
PQ0587 - antigen-4.153 Signal-induced upregulation of MMP-9 results
PQ0588 - in a release of sKitL, conferring signals that enhance
PQ0589 - mobility of progenitor cells into a vascular-enriched niche
PQ0590 - favoring liberalization of the cells into the
PQ0591 - circulation.154
PQ0593 - ..
PQ0594 - 10. How can we explain the exercise-induced mobilization of
PQ0595 - EPCs?
PQ0597 - ..
PQ0598 - In several studies, it was demonstrated that exercise
PQ0599 - increases the concentration of NO,132 which in turn can
PQ0600 - activate MMP-9 in bone marrow,155 leading to enhanced
PQ0601 - mobilization of progenitor cells, as depicted above. As
PQ0602 - soon as the EPCs are circulating, the most important
PQ0603 - factors for tissue engraftment of the mobilized cells are
PQ0604 - the local concentration of stromal-derived factor-1? and
PQ0605 - its cell receptor CXCR4.156 This notion is further
PQ0606 - supported by the observation that mice lacking CXCR4 die in
PQ0607 - utero because of defects in vascular development.157
PQ0608 - Although the animal data make shear stress-induced NO
PQ0609 - generation a likely mechanism for NO-mediated EPC
PQ0610 - mobilization, animal experiments with ischemic exercise are
PQ0611 - still lacking. Therefore, the aforementioned controversy
PQ0612 - still awaits experimental resolution.
PQ0613 -
PQ0615 - ..
PQ0616 - Exercise Extended Endurance Regresses Atherosclerosis Plaque
PQ0617 - Atherosclerosis Plaque Regresses Extended Endurance Exercise
PQ0618 - Extended Endurance Exercise Regresses Atherosclerosis Plaque
PQ0619 -
PQ0620 -
PQ0621 - 11. Exercise and Plaque Regression in CAD
PQ0622 -
PQ0623 - Although it is high on the agenda in lipid research, plaque
PQ0624 - regression ceased to be a research focus of exercise
PQ0625 - research in recent years. Two decades ago, a series of
PQ0626 - angiographic long-term follow-up studies documented that
PQ0627 - regular endurance exercise training can retard the
PQ0628 - progression of coronary atherosclerosis158,159 or even
PQ0629 - reduce stenosis diameter if combined with lipid-management
PQ0630 - techniques of smoking cessation and other lifestyle
PQ0631 - interventions.160,161 Surprisingly, not a single study has
PQ0632 - addressed exercise-mediated changes in plaque volume by
PQ0633 - intravascular ultrasound thus far to control the findings
PQ0634 - of the early regression studies with a more accurate
PQ0635 - technique, which also permits insight into changes of
PQ0636 - plaque composition.
PQ0638 - ..
PQ0639 - Atherosclerotic plaque regression through regular endurance exercise
PQ0640 - training may have ceased to be a focus of research studies noted in
PQ0641 - this article, ref SDS 0 XY7L, because getting enough subjects with
PQ0642 - time and capacity may be difficult. Generally, patients retired or
PQ0643 - unable to work due to medical impairments have time available every
PQ0644 - day, but often lack capacity to perform daily endurance exercise at a
PQ0645 - level sufficient to trigger increase in HDL and EPCs. Patients with
PQ0646 - capacity for endurance exercise training at a level sufficient to
PQ0647 - increase HDL and EPCs lack the time to perform daily endurance
PQ0648 - training because of obligations to work and family life.
PQ0649 -
PQ0650 - [...above on 131125 0005 another article presents theory
PQ0651 - and practice finding elevated HDL and EPCs cause rapid
PQ0652 - regression of atherosclerotic plaques. ref SDS 0 6S7F
PQ0653 -
PQ0655 - ..
PQ0656 - Article Exercise in Cardiovascular Disease continues...
PQ0657 -
PQ0658 - 12. Conclusion
PQ0659 -
PQ0660 - To summarize, cardiac effects of exercise include an
PQ0661 - improved protection against I/R injury primarily as a
PQ0662 - result of higher antioxidative protection and improved LV
PQ0663 - diastolic and systolic function in chronic heart failure
PQ0664 - due to favorable changes in neurohormonal state,
PQ0665 - activation of PI3K (p110?) attenuating pathological
PQ0666 - hypertrophy, normalization of cardiomyocyte calcium
PQ0667 - handling, and inhibition of the catabolic
PQ0668 - ubiquitin-proteasome system.
PQ0670 - ..
PQ0671 - 13. Vascular effects are based on improved endothelium-mediated
PQ0672 - flow-induced vasodilatation in conduit arteries and larger
PQ0673 - resistance arteries, higher myogenic control, and increased
PQ0674 - metabolic vasodilatation in small resistance arteries.
PQ0675 - Vascular regeneration by mobilization of endothelial
PQ0676 - progenitor cells is augmented by exercise. Recently,
PQ0677 - improved endothelial vasodilatation has also been confirmed
PQ0678 - in the pulmonary artery.
PQ0679 -
PQ0680 - [On 140515 2043 letter to VA requests adding EPC to
PQ0681 - supplemental lab for Electrolyte Panel (Chem Profile),
PQ0682 - and for the purpose of evaluating prospects for
PQ0683 - regression of atherosclerotic plaques. ref SDS 64 YM61
PQ0685 - ..
PQ0686 - [On 140520 0732 letter to VA notifies Doctor Alba about
PQ0687 - adding EPC to follow up lab ordered to test Electrolyte
PQ0688 - panel (Chem Profile). ref SDS 67 4U46
PQ0690 - ..
PQ0691 - [On 140520 0732 at 1028 letter from Doctor Alba requests
PQ0692 - clarification for adding EPC to lab order. ref SDS 67
PQ0693 - 654J Called to explain scope of EPC lab, but encountered
PQ0694 - poor connection using cell phone. ref SDS 67 U63N
PQ0696 - ..
PQ0697 - [On 140626 1652 letter notifies VA of case studies
PQ0698 - showing failure to perform timely testing causes
PQ0699 - negative patient outcomes. ref SDS 68 MY51 VA reference
PQ0700 - to patient having vessel plaques 5 years ago, begs the
PQ0701 - question of testing to determine currently how much
PQ0702 - plaque, and level of care required, if any, to treat
PQ0703 - current condition. ref SDS 68 MZ33 Evidence shows CTA
PQ0704 - common procedure to evaluate current condition post CABG
PQ0705 - surgery. ref SDS 68 MZ54
PQ0707 - ..
PQ0708 - [On 140703 1938 Doctor Alba reports EPC issue discussed
PQ0709 - among team at VA in detail; determined no justification
PQ0710 - to evaluate EPC toward coronary CTA to assess regression
PQ0711 - of atherosclerosis, ref SDS 69 H167, which VA maintains
PQ0712 - requires treatment, shown in Progress Notes on 140519
PQ0713 - 0800, ref SDS 66 OW76, based solely on history of
PQ0714 - atherosclerosis requiring CABG x4 surgery on 091022, 5
PQ0715 - years ago, as presented in VA Progress Notes on 140519
PQ0716 - 0800, ref SDS 66 OW49, and without knowledge of actual
PQ0717 - current condition resulting from intervening events,
PQ0718 - e.g., 120% rise from HDL 30 to HDL 67, shown in labs on
PQ0719 - 140514 0950. ref SDS 61 W25L
PQ0721 - ..
PQ0722 - 14. Extending our concept of molecular mechanisms of exercise
PQ0723 - is essential to further optimize training interventions
PQ0724 - with regard to their clinical efficacy and to identify
PQ0725 - novel targets for pharmaceutical intervention. However,
PQ0726 - certain areas (ie, microcirculation and the venous system)
PQ0727 - are still incompletely understood and merit further
PQ0728 - molecular studies. Residual incomplete molecular
PQ0729 - understanding should not prevent the clinical use of
PQ0730 - training interventions with established clinical benefit.
PQ0732 - ..
PQ0733 - This article notes conceptual correlation between endurance exercise
PQ0734 - at system signal levels and production of EPS, required for
PQ0735 - endothelial layer repair of circulatory system that removes
PQ0736 - atherosclerosis plaques, cited in articles above. ref SDS 0 Z49G
PQ0737 -
PQ0738 -
PQ0739 -
PQ0740 -
PQ08 -
SUBJECTS
Default Null Subject Account for Blank Record
PR03 -
PR0401 - ..
PR0402 - Another article....
PR0404 - ..
PR0405 - Atherosclerosis Blocked Arteries Grow Branch Collateral Blood Vessels
PR0406 - Collateral Blood Vessels Grow Around Main Arteries Blocked by Plaque
PR0407 - Branch Blood Vessels Grow to Maintain Flow to Heart When Main Arteries Blocked
PR0408 -
PR0409 -
PR0410 - Harvard Health Publishing
PR0411 - Harvard Medical School
PR0413 - ..
PR0414 - Do-it-yourself bypass
PR0415 -
PR0416 - https://www.health.harvard.edu/newsletter_article/do-it-yourself-bypass
PR0418 - ..
PR0419 - Blood vessels respond to the slow, stealthy attack of
PR0420 - artery-clogging atherosclerosis by generating a host of
PR0421 - chemical and physical signals. An immediate action of these
PR0422 - signals is to improve blood flow beyond the narrowing. They
PR0423 - also bulk up tiny blood vessels that have been sitting idly in
PR0424 - the heart since birth. As these collateral vessels grow
PR0425 - larger, more muscular, and more interconnected, they begin to
PR0426 - reroute some of the blood flow around the blockage (see
PR0427 - "Growing around blocked arteries"). Such a natural bypass can
PR0428 - keep the heart well supplied with oxygen-rich blood, much as
PR0429 - its surgical counterpart can do.
PR0430 -
PR0431 -
PR0433 - ..
PR0434 - Another article....
PR0435 -
PR0436 - can branch vessels emerge to supply blood into the heart as
PR0437 - main arteries become blocked?
PR0438 -
PR0439 -
PR0440 - https://www.sciencedirect.com/topics/medicine-and-dentistry/angiogenesis
PR0441 -
PR0442 -
PR0443 -
PR0444 -
PR0445 -
PR05 -
SUBJECTS
Default Null Subject Account for Blank Record
PS03 -
PS0401 - ..
PS0402 - Endothelial Progenitor Cells and HDL Regress Atherosclerosis
PS0403 - HDL EPC Elevated Causes Rapid Regression Atherosclerosis
PS0404 - EPC HDL Elevated Causes Rapid Regression Atherosclerosis
PS0405 - Atherosclerosis Elevated HDL EPC Causes Rapid Regression
PS0406 -
PS0407 -
PS0408 - Another article says...
PS0410 - ..
PS0411 - NIH
PS0412 - Experimental & Clinical Cardiology
PS0414 - ..
PS0415 - An integrated approach for the mechanisms responsible for
PS0416 - atherosclerotic plaque regression
PS0417 - ---------------------------------------------------------
PS0418 -
PS0419 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209544/
PS0420 -
PS0421 - by Andrew A Francis, BSc and Grant N Pierce, PhD FACC FAHA
PS0422 - FISHR FIACS FCAHS FRSM FAPS
PS0424 - ..
PS0425 - Exp Clin Cardiol. 2011 Fall; 16(3): 77?86.
PS0427 - ..
PS0428 - PMCID: PMC3209544
PS0430 - ..
PS0431 - Review
PS0433 - ..
PS0434 - Institute of Cardiovascular Sciences, St Boniface Hospital
PS0435 - Research Centre, Department of Physiology, Faculties of
PS0436 - Medicine and Pharmacy, University of Manitoba, Winnipeg,
PS0437 - Manitoba
PS0439 - ..
PS0440 - Correspondence: Dr Grant N Pierce, Institute of Cardiovascular
PS0441 - Sciences, St Boniface Hospital Research Centre, 351 Tache
PS0442 - Avenue, Winnipeg, Manitoba R2H 2A6. Telephone 204-235-3206,
PS0443 - fax 204-235-0793, e-mail gpierce/at/sbrc.ca
PS0445 - ..
PS0446 - Received July 25, 2011; Accepted July 27, 2011.
PS0447 -
PS0448 - 1. Abstract
PS0449 -
PS0450 - Atherosclerosis was originally considered to be an ongoing
PS0451 - process that was inevitably associated with age. However,
PS0452 - plaques are highly dynamic, and are able to progress,
PS0453 - stabilize or regress depending on their surrounding milieu.
PS0454 - A great deal of research attention has been focused on
PS0455 - understanding the involvement of high-density lipoprotein
PS0456 - (HDL) in atherosclerotic plaque regression. However,
PS0457 - atherosclerotic plaque regression encompasses a variety of
PS0458 - processes that can be grouped into three main areas:
PS0459 - removal of lipids and necrotic material; restoration of
PS0460 - endothelial function and repair of denuded areas; and
PS0461 - cessation of vascular smooth muscle cell proliferation and
PS0462 - phenotype reversal. In addition to the role of
PS0463 - high-density lipoproteins (HDL) in lipid removal, resident
PS0464 - macrophages and foam cells are able to regain motility and
PS0465 - rapidly migrate on milieu improvement, moving both lipids
PS0466 - and necrotic material to regional lymph nodes.
PS0467 - Neighbouring endothelial cells can proliferate and replace
PS0468 - dead and dysfunctional cells. Circulating endothelial
PS0469 - progenitor cells can similarly restore vessel function.
PS0470 - Finally, abrogation of smooth muscle cell proliferation
PS0471 - occurs secondarily to these processes. This information is
PS0472 - integrated in the current article to present a
PS0473 - comprehensive and clear depiction of plaque regression.
PS0474 - This integrated view of regression is essential to optimize
PS0475 - the pharmaceutical targeting of the many processes and
PS0476 - pathways involved in plaque regression.
PS0477 -
PS0478 - [On 140626 1652 letter notifies VA of case studies
PS0479 - showing failure to perform timely testing causes
PS0480 - negative patient outcomes. ref SDS 68 MY51 VA reference
PS0481 - to patient having vessel plaques 5 years ago, begs the
PS0482 - question of testing to determine currently how much
PS0483 - plaque, and level of care required, if any, to treat
PS0484 - current condition. ref SDS 68 MZ33 Evidence shows CTA
PS0485 - common procedure to evaluate current condition post CABG
PS0486 - surgery. ref SDS 68 MZ54
PS0488 - ..
PS0489 - [On 140703 1938 Doctor Alba reports EPC issue discussed
PS0490 - among team at VA in detail; determined no justification
PS0491 - to evaluate EPC toward coronary CTA to assess regression
PS0492 - of atherosclerosis, ref SDS 69 H167, which VA maintains
PS0493 - requires treatment, shown in Progress Notes on 140519
PS0494 - 0800, ref SDS 66 OW76, based solely on history of
PS0495 - atherosclerosis requiring CABG x4 surgery on 091022, 5
PS0496 - years ago, as presented in VA Progress Notes on 140519
PS0497 - 0800, ref SDS 66 OW49, and without knowledge of actual
PS0498 - current condition resulting from intervening events,
PS0499 - e.g., 120% rise from HDL 30 to HDL 67, shown in labs on
PS0500 - 140514 0950. ref SDS 61 W25L
PS0502 - ..
PS0503 - 2. Atherosclerosis emerged as a major health dilemma during
PS0504 - the early 20th century. Nearly a full century later,
PS0505 - atherosclerosis has become the leading cause of death
PS0506 - worldwide (1,2). It is now understood that atherosclerotic
PS0507 - lesions are produced from a complex array of molecular and
PS0508 - cellular events that act in concert to form asymmetric
PS0509 - focal thickenings of the arterial tunica intima (3,4).
PS0511 - ..
PS0512 - 3. Atherosclerosis is initiated by the response of endothelial
PS0513 - cells (ECs) to injury caused by myriad noxious stimuli
PS0514 - including hyperglycemia, hypertension, hyperlipidemia,
PS0515 - infectious agents, obesity, modified lipoproteins,
PS0516 - homocysteine, nicotine, free radicals, altered changes in
PS0517 - arterial blood flow shear stress and normal spontaneous
PS0518 - metabolic damage (5?10). This initial damage induces a
PS0519 - loss of basal endothelial homeostasis causing endothelial
PS0520 - dysfunction (11). The resulting increase in endothelial
PS0521 - permeability permits the accumulation of low-density
PS0522 - lipoprotein (LDL) and cellular debris within the tunica
PS0523 - intima of the vessel wall, eventually leading to
PS0524 - endothelial activation. Once activated, ECs produce an
PS0525 - array of chemoattractant cytokines such as monocyte
PS0526 - chemoattractant protein-1, macrophage colony-stimulating
PS0527 - factor, interferon-?, platelet-endothelial cell adhesion
PS0528 - molecule-1, interleukin (IL)-1, IL-6 and tumour necrosis
PS0529 - factor-? (TNF-?), creating a proinflammatory environment
PS0530 - that attracts circulating monocytes and T lymphocytes
PS0531 - (12?14). Normally, ECs do not express molecules that
PS0532 - facilitate the adhesion of circulating leukocytes.
PS0533 - However, activated ECs express vascular cell adhesion
PS0534 - molecules such as intercellular adhesion molecules (ICAMs),
PS0535 - E-selectin and P-selectin, which mediate leukocyte adhesion
PS0536 - and infiltration (12,13). Endothelial-derived cytokines
PS0537 - subsequently drive the differentiation of monocytes into
PS0538 - macrophages, which use pattern recognition receptors to
PS0539 - sequester LDL, modified LDL, free cholesterol (FC) and
PS0540 - cholesteryl esters (3). Together, activated leukocytes and
PS0541 - ECs continue to produce proinflammatory cytokines and
PS0542 - growth factors that promote the transition of smooth muscle
PS0543 - cells from a quiescent, contractile phenotype to an active
PS0544 - and proliferative synthetic phenotype that deposits
PS0545 - extracellular matrix at the site of injury, forming a
PS0546 - fibrous cap (15?18). Continued exposure to various
PS0547 - noxious stimuli, in conjunction with a proinflammatory
PS0548 - environment, further exacerbates plaque severity,
PS0549 - perpetuates plaque progression, and promotes plaque
PS0550 - destabilization, resulting in plaque rupture which
PS0551 - manifest as acute events such as stroke or myocardial
PS0552 - infarction (19,20).
PS0554 - ..
PS0555 - 4. During the past few decades, an improved understanding of
PS0556 - atherosclerotic pathophysiology has enabled researchers to
PS0557 - consider the possibility of inducing plaque regression in
PS0558 - addition to the more conventional therapeutic goal of
PS0559 - reducing plaque progression. Traditionally,
PS0560 - atherosclerosis was viewed as an inevitable unidirectional
PS0561 - process that begins in childhood and manifests during
PS0562 - adulthood (20). However, during the 1980s, Badimon et al
PS0563 - (21) showed that plaque development is not simply a
PS0564 - permanent process associated with age, but rather a dynamic
PS0565 - process that can be slowed, stopped or reversed. In spite
PS0566 - of the evidence supporting the existence of plaque
PS0567 - regression, the concept of "plaque regression" was resisted
PS0568 - for decades. Critics of regression asserted that the
PS0569 - physical attributes of an atherosclerotic plaque, including
PS0570 - calcification, necrosis and fibrosis, indicated stability,
PS0571 - and the molecular processes associated with plaques such as
PS0572 - oxidative damage, cell proliferation and transformation
PS0573 - seemed to imply that regression would be very difficult or
PS0574 - impossible to achieve. Furthermore, at that time, a
PS0575 - majority of animal studies attempting to induce regression
PS0576 - in advanced plaques had failed (22?26).
PS0577 -
PS0578 - [On 200124 0705 IVUS found completely clear (stenosis 0)
PS0579 - 11 years after CABG x4 and after raising HDL 30 at time
PS0580 - of CABG, to HDL 83 on 181112, demonstrates method and
PS0581 - results raising HDL > 60. ref SDS 87 ME8G
PS0583 - ..
PS0584 - 5. However, the ability of even advanced lesions to regress on
PS0585 - robust reductions in LDL levels and increases in
PS0586 - high-density lipoprotein (HDLs) levels has established
PS0587 - plaque regression as a well-accepted process (27,28).
PS0588 - Atherosclerosis is now known as a highly dynamic process in
PS0589 - which plaques are able to either progress or regress,
PS0590 - depending on the surrounding milieu (29,30). However,
PS0591 - despite the plethora of research, a comprehensive
PS0592 - discussion that incorporates and integrates the current
PS0593 - knowledge of the various processes known to occur during
PS0594 - plaque regression remains to be completed.
PS0596 - ..
PS0597 - Atherosclerosis plaque regression is now a "well established process"
PS0598 - on "robust" reduction of LDL - does this correlate with LDL-P < 1000
PS0599 - or LDL-C < 70 - at this time the matter is not addressed in the
PS0600 - research?? Or, does "robust reduction of LDL" simply correlate to HDL
PS0601 - reaching sufficiently elevated level (i.e., >= 60) for "reverse
PS0602 - cholesterol transport" (RTC) to occur, discussed in this artical 2
PS0603 - paragraphs below? ref SDS 0 HG7N
PS0605 - ..
PS0606 - Correlating regression of atherosclerosis plaque solely on robust
PS0607 - reduction of LDL and increase of HDL further seems to ignore the role
PS0608 - of increasing EPCs, cited initially and extensively in the same
PS0609 - article below. ref SDS 0 FV5L
PS0611 - ..
PS0612 - Article continues...
PS0613 -
PS0614 - 6. What is atherosclerotic plaque regression? Ideally, plaque
PS0615 - regression would be the return of the arterial wall to its
PS0616 - initial state. However, with the exception of fatty
PS0617 - streaks, even under ideal conditions, the complete reversal
PS0618 - of plaque formation does not occur (30). It is important
PS0619 - to understand that plaque regression is not simply plaque
PS0620 - progression in reverse. Rather, the mechanisms of plaque
PS0621 - regression are distinct and are composed of three important
PS0622 - processes: the reduction or clearance of necrotic and
PS0623 - extracellular material from the tunica intima; endothelial
PS0624 - repair, regeneration and return to homeostasis; and the
PS0625 - cessation of smooth muscle cell proliferation (Figure 1).
PS0626 - Although a reduction of luminal area, plaque volume or
PS0627 - intimal medial thickness are indexes commonly used in
PS0628 - diagnostic medicine to assess plaque regression, and are
PS0629 - possible estimations of regression, they are currently
PS0630 - unable to capture the true complexity of this process.
PS0631 -
PS0632 - [On 200124 0705 IVUS found completely clear (stenosis 0)
PS0633 - 11 years after CABG x4 and after raising HDL 30 at time
PS0634 - of CABG, to HDL 83 on 181112, demonstrates method and
PS0635 - results raising HDL > 60. ref SDS 87 ME8G
PS0636 -
PS0638 - ..
PS0639 - 7. REMOVAL OF EXTRACELLULAR AND INTRACELLULAR LIPIDS AND
PS0640 - NECROTIC MATERIAL
PS0642 - ..
PS0643 - Although the mechanisms of regression are beginning to be
PS0644 - understood, there has been considerable progress in
PS0645 - isolating the important players in regression and
PS0646 - understanding their biological role. Attention, however,
PS0647 - within the past few decades has been focused on reverse
PS0648 - cholesterol transport (RCT) and its major player, HDL.
PS0650 - ..
PS0651 - 8. Plaque Regression - Reverse Cholesterol Transport - RCT
PS0652 - Reverse Cholesterol Transport - RCT - Regresses Plaque
PS0653 - HDL and its influence on atherosclerotic plaque regression though RCT
PS0654 -
PS0655 - HDL classification: Since the early 1970s, HDL cholesterol
PS0656 - (HDL-C) has been associated with a decrease in
PS0657 - cardiovascular disease (CVD) (31). Gordon et al (32)
PS0658 - demonstrated that there is an inverse relationship between
PS0659 - systemic levels of HDL-C and the prospective risk for
PS0660 - coronary artery disease; this correlation was maintained
PS0661 - even at very low levels of LDL cholesterol. Animal and
PS0662 - human studies have shown that infusions of synthetic HDL
PS0663 - particles can induce regression of atherosclerotic plaque
PS0664 - (21,33,34). Moreover, increases in HDL-C by even 1 mg/dL
PS0665 - are associated with a 3% to 4% decrease in
PS0666 - cardiovascular-related mortality (35). Since the discovery
PS0667 - of the inverse relationship of HDL-C with CVD, a large
PS0668 - amount of information has been obtained about its structure
PS0669 - and function. Although the full mechanism of HDL's
PS0670 - anti-atherosclerotic effects are not well known, it is
PS0671 - becoming clear that HDL participates in ameliorating nearly
PS0672 - all aspects of plaque pathogenicity by restoring
PS0673 - endothelial cell basal function, decreasing smooth muscle
PS0674 - cell proliferation and migration, and decreasing
PS0675 - intraplaque inflammation and cellular debris retention
PS0676 - (36). It has also become clear that not only is the
PS0677 - concentration of HDL within the circulation important for
PS0678 - its anti-inflammatory effect, but also its quality (37).
PS0679 - Nevertheless, what has been well established is HDL's
PS0680 - contribution to atherosclerotic plaque regression by
PS0681 - promoting RCT. However, to understand the RCT pathway, it
PS0682 - is essential to become aware of the various structures of
PS0683 - HDL.
PS0684 -
PS0685 - [On 230919 1230 Doctor Iannuzzi vascular surgeon
PS0686 - comments on CT saying..."aorta measures 2.6 cm. The
PS0687 - plaque irregularity has progressed compared to 2009,
PS0688 - although has been stable over the past 2 years"... while
PS0689 - patient hiking 15 - 30 miles per day and HDL 55 - 65,
PS0690 - with EPCs assumed comparably elevated. ref SDS 88 GP3I
PS0692 - ..
PS0693 - 9. HDLs were first discovered by Gofman et al (38) in
PS0694 - experimental studies using analytical ultracentrifugation
PS0695 - to separate and categorize distinct serum lipoprotein
PS0696 - families according to their hydrated density. HDLs were
PS0697 - defined as lipoproteins of small diameter (5 nm to 17 nm)
PS0698 - that sediment in the density region (1.063 g/mL to 1.21
PS0699 - g/mL) (Table 1). It is now understood that HDL is a highly
PS0700 - heterogeneous group of particles, and composed of many
PS0701 - subclasses. The difference between HDL subclasses is
PS0702 - ultimately dependent on the particles' physical properties
PS0703 - including shape, size, density and charge; however, these
PS0704 - subclasses can be reclassified according to differences in
PS0705 - lipid transfer proteins, enzymes, lipid content and
PS0706 - apolipoproteins (39,40). Many methods have been developed
PS0707 - to separate HDL into its various subclasses. Gofman et al
PS0708 - (38) developed an analytical ultracentrifugation method for
PS0709 - identifying the distinct subclasses of HDL particles, which
PS0710 - is currently the gold standard technique for HDL subclass
PS0711 - determination (41,42). Using this technique and other
PS0712 - ultracentrifugation methods, such as rate-zonal or single
PS0713 - vertical spin ultracentrifugation, HDLs can be separated
PS0714 - into two main subfractions based on their respective
PS0715 - densities: HDL2 (1.063 g/mL to 1.125 g/mL) and HDL3
PS0716 - (>1.125 g/mL to 1.21 g/mL) (43?45). These two HDL
PS0717 - subfractions can also be further subdivided based on their
PS0718 - size (diameter) using nondenaturing polyacrylamide gel
PS0719 - electrophoresis, yielding HDL2b (9.7 nm to 12.0 nm), HDL2a
PS0720 - (8.8 nm to 9.7 nm), HDL3a (8.2 nm to 8.8 nm), HDL3b (7.8 nm
PS0721 - to 8.2 nm) and HDL3c (7.2 nm to 7.8 nm) (46). Another
PS0722 - classification system of HDL arose with the use of agarose
PS0723 - gel electrophoresis, separating HDL based on relative
PS0724 - negative surface charge density. ?-HDL, which comprises the
PS0725 - majority of plasma HDL, has a high negative charge density
PS0726 - compared with pre?-HDL, also known as nascent HDL (47?49).
PS0727 - Two-dimensional electrophoresis, which combines both
PS0728 - agarose gel and gradient gel electrophoresis, can further
PS0729 - resolve -HDL and pre-HDL into 12 distinct HDL subclasses
PS0730 - based on their size and motilities with respect to albumin:
PS0731 - pre- (pre-1, pre-2 and pre-3), - (-1, -2 and ?-) and pre-
PS0732 - (pre-1, pre-2 and pre-3) (48,50). Finally, HDL can be
PS0733 - classified by immunoaffinity methods according to its
PS0734 - apolipoprotein (apo) A composition. The majority of
PS0735 - proteins found in HDL are either apoAI (65% to 70%) and
PS0736 - apoAII (20% to 25%). Furthermore, two major
PS0737 - apoA-containing HDL subclasses exist: HDL particles may
PS0738 - contain both apoAI and apoAII in a 2:1 molar ratio, or they
PS0739 - can contain only apoAI (50,51). Adding to HDL?s
PS0740 - complexity, several proteins have been shown to circulate
PS0741 - in the plasma bound to HDL including apoA-IV, apoC, apoE,
PS0742 - apoF, lecithin:cholesterol acyltransferase, cholesteryl
PS0743 - ester transferase (CETP), phospholipid transferase
PS0744 - protein, paraoxonase and platelet-activating factor
PS0745 - acetylhydrolase. Moreover, proteomic analyses have shown
PS0746 - that HDL may contain more than 48 proteins. It is
PS0747 - generally accepted that the majority of plasma HDL is in
PS0748 - the form of pre?-HDL, as well as HDL2 and HDL3 ? the
PS0749 - mature forms of HDL that are equivalent to ?-HDL (52,53)
PS0750 - (Table 1). Despite the many different classifications of
PS0751 - HDL, all HDL particles have in common their ability to
PS0752 - mediate the process of RCT.
PS0753 -
PS0754 - [On 230919 1230 Doctor Iannuzzi vascular surgeon
PS0755 - comments on CT saying..."aorta measures 2.6 cm. The
PS0756 - plaque irregularity has progressed compared to 2009,
PS0757 - although has been stable over the past 2 years"... while
PS0758 - patient hiking 15 - 30 miles per day and HDL 55 - 65,
PS0759 - with EPCs assumed comparably elevated. ref SDS 88 GP3I
PS0761 - ..
PS0762 - 10. RCT: According to the generally accepted definition of
PS0763 - RCT, the first step of RCT is the efflux of extrahepatic
PS0764 - cholesterol from intracellular cholesterol pools. This
PS0765 - usually focuses on the removal of cholesterol from
PS0766 - macrophages. Alternatively, critics of this view attest
PS0767 - that assembly of HDL particles and their subsequent
PS0768 - secretion into the circulation is the initial step of this
PS0769 - process (54?56). In the present review, however, the
PS0770 - overview of HDL's involvement in RCT will begin with the
PS0771 - production and release of HDL to provide a clear synopsis
PS0772 - of RCT. Despite the disagreement regarding the initial
PS0773 - steps in RCT, it is accepted that the acquisition of
PS0774 - cholesterol from peripheral stores by HDL is the major
PS0775 - mechanism for promoting atherosclerotic plaque regression.
PS0776 -
PS0778 - ..
PS0779 - Liver Produces HDL and Secondarily Small Intestine
PS0780 -
PS0781 - 11. The production of all HDL subclasses begins with the
PS0782 - synthesis of apoAI and apoAII. These proteins are
PS0783 - primarily generated in the liver and secondarily by the
PS0784 - small intestine (56,57). Both hepatocytes and enterocytes
PS0785 - can secrete lipid-poor apoAI and AII into the circulation,
PS0786 - where it acquires phospholipids and cholesterol to form
PS0787 - pre?-HDL (58?60). Regardless, the majority of apoA
PS0788 - produced in the intestine is packaged into chylomicrons,
PS0789 - which are eventually internalized by the liver. In
PS0790 - contrast, hepatocyte apoA secretion into plasma is more
PS0791 - complex. Similar to chylomicrons, very low density
PS0792 - lipoprotein (VLDL) ? another triglyceride-rich lipoprotein
PS0793 - ? can lose cholesterol. Phospholipids can also lose or
PS0794 - gain apolipoproteins during lipolysis, which generates
PS0795 - pre?-HDL. VLDL can also be amalgamated into HDL2 and HDL3
PS0796 - (61). Finally, hepatocytes can synthesize and secrete both
PS0797 - apoA and pre?-HDL directly into the circulation. In spite
PS0798 - of the different modes of release, once in the
PS0799 - circulation, pre?-HDL can be used for RCT.
PS0801 - ..
PS0802 - 12. The first and rate-limiting steps of RCT is cholesterol
PS0803 - efflux from macrophages, and the peripheral tissue to the
PS0804 - HDL particle (62). There are currently four proposed
PS0805 - mechanisms of cholesterol efflux into lipid-poor apoAI and
PS0806 - the various HDL particles: aqueous diffusion, scavenger
PS0807 - receptor class B type 1 (SR-BI)-mediated efflux,
PS0808 - ATP-binding cassette (ABC) transporter A1-mediated efflux
PS0809 - and ABCG1-mediated efflux (54,55).
PS0811 - ..
PS0812 - 13. First, cholesterol efflux can occur passively by adhering
PS0813 - to its concentration gradient. As a result, the passive
PS0814 - diffusion pathway is bidirectional, and the rate-limiting
PS0815 - step of this process is dependent on the ratios and
PS0816 - interactions between the FC in the donor cells and the
PS0817 - phospholipids within the plasma membrane of the acceptor
PS0818 - molecule ? the HDL particle (62,63). The kinetics of this
PS0819 - interaction are accelerated by higher proportions of
PS0820 - unsaturated phospholipids and decreases in the
PS0821 - sphingomyelin content of the plasma membrane (64,65).
PS0822 - Because cholesterol efflux by this pathway is not affected
PS0823 - by HDL particle size, all HDL subclasses are equal in their
PS0824 - ability to accept cholesterol through aqueous diffusion
PS0825 - (66).
PS0827 - ..
PS0828 - 14. In contrast to aqueous diffusion, the remaining three
PS0829 - cholesterol efflux pathways are mediated by protein-protein
PS0830 - interactions. Cholesterol efflux can be mediated by the
PS0831 - ATP-independent, passive SR-BI pathway. Cholesterol
PS0832 - transport is initiated by the binding of HDL to SR-BI,
PS0833 - which subsequently forms a hydrophobic channel allowing
PS0834 - efflux to occur (67). SR-BI promotes efflux exclusively to
PS0835 - larger, more mature HDL particles such as HDL2 and HDL3,
PS0836 - which can further increase the SR-BI-mediated selective
PS0837 - uptake of cholesterol if they contain apoAII (68). Because
PS0838 - this process is bidirectional, HDL may be a donor and an
PS0839 - acceptor of cholesterol. Thus, its role in aiding RCT in
PS0840 - macrophages may not be as important as the remaining
PS0841 - energy-dependent cholesterol efflux pathways (69).
PS0843 - ..
PS0844 - 15. Cholesterol and phospholipid efflux to apoAI is promoted
PS0845 - by the interaction of ABCA1 with pre?-HDL or with
PS0846 - lipid-poor apoAI (49). The activation of ABCA1 induces the
PS0847 - removal of cholesterol from the plasma membrane of the
PS0848 - donor cell and can also cause efflux from intracellular
PS0849 - cholesterol pools (70,71). The rate of lipid efflux is
PS0850 - dependent on the concentration of activated ABCA1 and on
PS0851 - the amount of unsaturated phospholipids in the donor cell
PS0852 - (72). In addition, the concentration of ABCA1 in the
PS0853 - plasma membrane is regulated by the interaction of apoA1
PS0854 - and ABCA1, which prevents its intracellular degradation
PS0855 - (73).
PS0857 - ..
PS0858 - 16. Another member of the ABC family of transporters, ABCG1,
PS0859 - is the last major efflux pathway in RCT. ABCG1, which is
PS0860 - involved with regulating intracellular cholesterol
PS0861 - homeostasis, interacts with all subclasses of HDL (74?76).
PS0862 - It also mediates cholesterol efflux through the
PS0863 - reorganization of existing cholesterol pools, and
PS0864 - increasing its diffusion to and uptake by HDL particles.
PS0865 - Although all HDL subclasses can mediate efflux through the
PS0866 - ABCG1 pathway, larger HDL particles are more effective
PS0867 - acceptors, as in the SR-BI efflux pathway (77).
PS0869 - ..
PS0870 - 17. Following the removal of cholesterol from peripheral sites,
PS0871 - HDL undergoes further maturation characterized by increased
PS0872 - particle size due to the progressive accumulation of
PS0873 - cholesterol (78). In circulation, cholesterol becomes
PS0874 - esterified to pre-HDL through an apoA1-mediated reaction
PS0875 - with lecithin:cholesterol acyltransferase, converting
PS0876 - lecithin and cholesterol into lysolecithin and CE (79).
PS0877 - Because CE are hydrophobic, they can move to the developing
PS0878 - core of the HDL particle, which causes it to enlarge and
PS0879 - become spherical. This ultimately transforms pre-HDL into
PS0880 - HDL3 or HDL2. This process not only increases the surface
PS0881 - area for FC acceptance, it also helps maintain the FC
PS0882 - gradient (69,80). Once a mature HDL particle is
PS0883 - synthesized, it has three possible fates. First, lipolytic
PS0884 - enzymes such as lipoprotein, hepatic and endothelial
PS0885 - lipases can hydrolyze triglycerides and phospholipids
PS0886 - causing apoAI to dissociate from HDL, which facilitates the
PS0887 - clearing of apoAI from circulation by the kidneys and the
PS0888 - conversion of mature HDL particles back into nascent
PS0889 - pre-HDL (81?83). Second, constituents of mature HDL
PS0890 - particles may be transported to other HDL subclasses or
PS0891 - other lipoproteins. For example, certain plasma lipid
PS0892 - transfer proteins can transfer triacylglycerol and
PS0893 - phospholipids among lipoproteins (84). CETP transfers the
PS0894 - majority of CEs to apoB-containing lipoproteins, such as
PS0895 - VLDL and LDL, which produces small cholesterol
PS0896 - ester-depleted HDL particles that are either cleared by the
PS0897 - kidneys or incorporated into another HDL particle forming a
PS0898 - large mature HDL particle (85). ApoB-containing
PS0899 - lipoproteins can be removed from the circulation by hepatic
PS0900 - LDL receptors and catabolized by the liver, and hepatic
PS0901 - SR-BI can also bind LDL and VLDL. Thus, the CETP pathway
PS0902 - is believed to be an important route of RCT (86?90).
PS0903 - However, clinical studies involving humans with CETP
PS0904 - deficiencies report conflicting and controversial results,
PS0905 - which ultimately has led to questioning of whether CETP is
PS0906 - detrimental or instrumental in CVD (19,91?94). It is also
PS0907 - likely that cholesterol transferred to LDL or VLDL can be
PS0908 - redeposited to peripheral tissue. Third, cholesterol can
PS0909 - be returned to the liver through the clearance of HDL from
PS0910 - the circulation. SR-BI, located on the surface of liver or
PS0911 - adrenal cells, recognizes circulating HDL particles and
PS0912 - facilitates the unloading of their FC and cholesterol
PS0913 - esters (95). This process does not involve the
PS0914 - internalization and degradation of the HDL particle. Thus,
PS0915 - removal of cholesterol and CEs produces nascent HDL
PS0916 - particles that have the potential to be recycled back into
PS0917 - the RCT pathway (85). As opposed to HDL efflux from
PS0918 - macrophages, SB-RI is the most abundant receptor on
PS0919 - hepatocytes, thus making this pathway an important mode of
PS0920 - cholesterol influx. An alternative method of influx
PS0921 - involves the acquisition of apoE enabling HDL to deliver
PS0922 - cholesterol to hepatic tissue through its interaction with
PS0923 - LDL receptors, which mediates the internalization of HDL
PS0924 - particles and their subsequent catabolism (96). Novel
PS0925 - routes to HDL holoparticle uptake by hepatocytes, such as
PS0926 - HDL internalization by the receptor P2Y13, continue to be
PS0927 - identified (97).
PS0929 - ..
PS0930 - 18. Cholesterol within hepatocytes must be secreted into the
PS0931 - intestinal lumen to complete the RCT pathway. The rate of
PS0932 - cholesterol excretion is dependent on several transporters
PS0933 - on its apical membrane. Cholesterol efflux into bile is
PS0934 - dependent on both SR-BI and the ABC family of
PS0935 - transporters. The rate of cholesterol efflux is primarily
PS0936 - controlled by ABCG5 and ABCG8 transporters (98,99).
PS0937 - Although SR-BI can also facilitate cholesterol secretion
PS0938 - into bile, it serves only a minor role on the apical
PS0939 - membrane, being secondary to the ABC transporters.
PS0940 - However, SR-BI is an important mode of influx on the
PS0941 - basolateral membrane of hepatocytes (100,101).
PS0943 - ..
PS0944 - 19. The hepatobiliary route of HDL-C removal is generally
PS0945 - accepted to be the major mode of cholesterol excretion.
PS0946 - However, Cheng and Stanley (102) suggested that there is
PS0947 - an additional route to fecal cholesterol loss through a
PS0948 - nonbiliary fecal route. Nonbiliary sterol loss is believed
PS0949 - to be regulated by the liver. Under conditions in which
PS0950 - the hepatic cholesterol load exceeds a manageable amount,
PS0951 - cholesterol is repackaged into plasma lipoproteins that
PS0952 - are bound for secretion by the intestines (103). Although
PS0953 - the mechanism of the nonbiliary fecal pathway is not well
PS0954 - understood, many aspects are shared with the hepatobiliary
PS0955 - route of sterol loss. It has been suggested that
PS0956 - lipoproteins responsible for the transport of cholesterol
PS0957 - to the intestine are either apoE-rich HDL or
PS0958 - apoB-containing lipoproteins (104,105). It is quite likely
PS0959 - that most lipoproteins are able to facilitate this process
PS0960 - because enterocytes express SB-RI on their basolateral
PS0961 - membrane (78). Similar to hepatocytes, enterocytes express
PS0962 - ABCG5/G8 as well as SR-BI on their apical membranes,
PS0963 - allowing the efflux of cholesterol from the enterocyte to
PS0964 - the intestinal lumen (106).
PS0966 - ..
PS0967 - 20. Monocyte/macrophage migration
PS0968 -
PS0969 - During regression, cholesterol removal is accompanied by
PS0970 - the disappearance of macrophage and foam cells. This is
PS0971 - one of the first noticeable indications of plaque
PS0972 - regression (30). It was initially believed that the
PS0973 - disappearance of monocytes and macrophages from
PS0974 - atherosclerotic plaques was only caused by apoptosis,
PS0975 - lysis in situ and phagocytosis by new macrophages.
PS0976 - However, it is now evident that macrophages within
PS0977 - atherosclerotic lesions can also regain motility and
PS0978 - migrate to regional lymph nodes when the local environment
PS0979 - improves.
PS0981 - ..
PS0982 - 21. Mechanisms of cell motility and immobilization: Cells
PS0983 - facilitate migration through cell motility cycling. This
PS0984 - process contains four sequential events beginning with the
PS0985 - following: polarization of the cell; extension of
PS0986 - lamellipodia at the leading edge; the formation of a focal
PS0987 - adhesion attaching the cell to the underlying substrate;
PS0988 - and the contraction and rear detachment of the cell
PS0989 - resulting in cell movement. The regulation of these events
PS0990 - is coordinated by the Rho family of GTPase (107). The
PS0991 - exchange of GDP for GTP activates Rho-GTPases, which
PS0992 - control cytoskeleton remodelling by activating downstream
PS0993 - targets (108). Two members of this family, RhoA ? a GTPase
PS0994 - associated with actin filament organization and promotion
PS0995 - of focal adhesions ? and Rac1 ? which induces
PS0996 - polymerization of actin that forms both lamellipodia and
PS0997 - membrane ruffles ? have important roles in cell
PS0998 - immobilization (109,110).
PS1000 - ..
PS1001 - 22. During atherosclerosis, macrophages within atherosclerotic
PS1002 - plaques accumulate FC and CEs (111?113). Accumulation of
PS1003 - cholesterol causes apoptosis and secondary necrosis in
PS1004 - macrophages and impairs chemotaxis. This immobilization is
PS1005 - associated with increased levels of Rac-GTP, the active
PS1006 - form of Rac, and reduced levels of RhoA. The translocation
PS1007 - of Rac to the plasma membrane facilitates its activation.
PS1008 - Cholesterol-rich domains within the inner leaflet of the
PS1009 - plasma membrane maintain Rac-GTP in the membrane. The loss
PS1010 - of proper cell polarization, cell spreading and plasma
PS1011 - membrane ruffling caused by increased Rac activity
PS1012 - abrogates forward movement of the cell (114?116).
PS1014 - ..
PS1015 - 23. Mechanisms of macrophage migration during plaque
PS1016 - regression: The migration of macrophage and foam cells
PS1017 - from atherosclerotic plaques is complex and is controlled
PS1018 - by plaque dynamics. Improvements in the plaque milieu
PS1019 - causes the transformation of macrophages from an
PS1020 - immobilized to a mobile state by the expression of
PS1021 - dendritic cell markers (117,118) such as chemokine (C-C
PS1022 - motif) receptor 7 (CCR7), an essential requirement for
PS1023 - dendrite cell migration (119). CCR7 control of immune cell
PS1024 - emigration is mediated by the activation and upregulation
PS1025 - of the liver X receptor (28). The downstream target of the
PS1026 - liver X receptor, ABCA1, is also unregulated (118).
PS1027 - Macrophage/foam cell migration and morphological
PS1028 - transformation can be, in part, facilitated by
PS1029 - ABCA1-induced cholesterol redistribution. ABCA1 may
PS1030 - decrease membrane cholesterol pools releasing Rac-GTP
PS1031 - (120,121). ABCG1 and LDL receptor-related protein 1 may
PS1032 - also play a small role in macrophage migration from
PS1033 - atherosclerotic plaques (119,122).
PS1035 - ..
PS1036 - 24. ENDOTHELIAL REPAIR, REGENERATION AND HOMEOSTASIS
PS1037 -
PS1038 - Vascular ECs serve as a dynamic barrier separating the
PS1039 - vessel wall from blood. They also control vascular
PS1040 - homeostasis by regulating vascular tone, leukocyte
PS1041 - trafficking and vessel permeability. Endothelial
PS1042 - dysfunction - an early hallmark of atherosclerosis - is
PS1043 - characterized by the conversion of ECs from a normal
PS1044 - physiological phenotype to a vasoconstrictive,
PS1045 - procoagulant, platelet-activating phenotype that
PS1046 - contributes to atherosclerosis (123,124). Prolonged
PS1047 - endothelial dysfunction can lead to cell apoptosis, which
PS1048 - can ultimately denude the vessel wall (125,126). To
PS1049 - achieve atherosclerotic regression, these dysfunctional ECs
PS1050 - must be returned to basal homeostasis and dead cells need
PS1051 - to be replaced. Currently, there are three known
PS1052 - mechanisms that can result in endothelial cell replacement:
PS1053 - circulating endothelial progenitor cells, local endothelial
PS1054 - cell proliferation and migration, and abrogation of
PS1055 - endothelial apoptosis.
PS1057 - ..
PS1058 - 25. Endothelial progenitor cells and vascular repair The term
PS1059 - "stem cell" or "progenitor cell" refers to immature cells
PS1060 - that have the ability to self-renew and differentiate into
PS1061 - a variety of cell types. Thus, these cells have the
PS1062 - potential to restore the function of damaged tissues
PS1063 - (127,128). Endothelial progenitor cells (EPCs), similar to
PS1064 - all progenitor cells, are lineage specific, and comprise a
PS1065 - highly heterogeneous population of cells capable of
PS1066 - differentiating exclusively into ECs (129). The majority
PS1067 - of progenitor cells mature from hemato-poietic stem cells.
PS1068 - These stem cells are mainly isolated from bone marrow,
PS1069 - peripheral blood and umbilical cord, but can be obtained
PS1070 - from the spleen, intestine, liver, adipose tissue and
PS1071 - adventitia (130). Regardless of their source, all
PS1072 - hematopoietic stem cells are CD34+ and CD133+.
PS1073 - Hematopoietic stem cells can also produce nonerythroid
PS1074 - myeloid and granulocyte-macrophage lineages, as well as
PS1075 - EPCs. Therefore, EPCs are characterized by the
PS1076 - co-expression of both hematopoietic stem cell markers and
PS1077 - endothelial markers such as vascular endothelial growth
PS1078 - factor receptor-2, CD31, endothelial nitric oxide (NO)
PS1079 - synthase, and vascular endothelial cadherin (130?134).
PS1080 - Although hematopoietic stem cells appear to be the main
PS1081 - source of EPCs, other resident bone marrow stem cells, such
PS1082 - as mesenchymal stem cells, may generate EPCs. In addition,
PS1083 - CD14+ myeloid subsets express both the hematopoietic and
PS1084 - endothelial markers, and CD14+ monocytic cells can
PS1085 - differentiate into ECs (135?138). EPCs are instrumental in
PS1086 - maintaining the integrity of the vascular endothelium,
PS1087 - which contribute to the regression of atherosclerotic
PS1088 - plaques.
PS1090 - ..
PS1091 - 26. To obtain any benefit from nontissue resident or
PS1092 - exogenously administered EPCs, they must be recruited by
PS1093 - and migrate to the site of injury. This process is
PS1094 - orchestrated by resident cells of the injured area. During
PS1095 - atherosclerosis, various cell types within the plaque are
PS1096 - capable of mobilizing and homing EPCs to denudated vessels.
PS1097 - First, EPCs are released from their source upon stimulation
PS1098 - from molecular signals produced by immune cells within the
PS1099 - plaque. Activated M2 type macrophages promote vessel
PS1100 - healing through the secretion of granulocyte
PS1101 - colony-stimulating factor (G-CSF) (139). G-CSF facilitates
PS1102 - the release of EPCs into circulation. In addition,
PS1103 - cytokine-mediated release of proteases such as elastase,
PS1104 - cathepsin G and matrix metalloproteinase (MMP)-9 discharges
PS1105 - EPCs by cleaving the adhesive interaction between EPCs and
PS1106 - stromal cells (134,140). The released EPCs are
PS1107 - subsequently homed to and mobilized by the injured area.
PS1108 - An important homing signal is the chemokine stromal
PS1109 - cell-derived factor-1 (SDF-1). Under normal conditions,
PS1110 - the bone marrow and many other tissues constitutively
PS1111 - express SDF-1. The bone marrow, however, produces a
PS1112 - gradient that favours the retention of EPCs. During
PS1113 - conditions of ischemia, inflammation and hypoxia, this
PS1114 - gradient is reversed by the expression of hypoxia-inducible
PS1115 - factor-1, which upregulates SDF-1 in injured tissues
PS1116 - (141-144). In addition, NO, estrogen, HDL, vascular
PS1117 - endothelial growth factor and erythropoietin contribute to
PS1118 - the increase in the plasma titre of EPCs and their
PS1119 - recruitment to the site of injury by augmenting the
PS1120 - phosphatidyl-inositol-3-phosphate (PIP3)/Akt pathway
PS1121 - (145-147). Once in the damaged area, cell adhesion
PS1122 - molecules, such as P/E-selectin and ICAM-1, mediate the
PS1123 - binding of EPCs to the injured endothelium (148). In
PS1124 - severely damaged vessels, exposed matrix proteins activate
PS1125 - platelets that adhere to the denuded area. Platelet
PS1126 - activation causes microthrombi formation and the expression
PS1127 - of SDF-1, targeting EPCs to the damaged endothelium.
PS1128 - Moreover, EPCs potentially adhere not only to the
PS1129 - endothelium, but also to platelets by interacting with
PS1130 - P-selectin and GPIIb integrin (149?151). After EPC
PS1131 - attachment, they differentiate into ECs under the influence
PS1132 - of the laminar shear stress of the blood (128,152).
PS1134 - ..
PS1135 - 27. Several studies have evaluated the beneficial effects of
PS1136 - EPCs on CVD. Bone marrow-derived EPCs can differentiate
PS1137 - into ECs and induce neovascularization in ischemic mouse
PS1138 - tissue (153,154). There is an inverse relationship between
PS1139 - circulating (CD34+ and CD133+) progenitor cells for both
PS1140 - modifiable and nonmodifiable atherosclerotic risk factors,
PS1141 - such as smoking and age (155). Moreover, low circulating
PS1142 - levels of EPCs are found in patients who are at high risk
PS1143 - of developing coronary artery disease (156). Statin
PS1144 - therapy, known to reduce the incidence of CVD and
PS1145 - cardiovascular events, was able to increase EPC titre and
PS1146 - engraftment efficiency (157,158).
PS1148 - ..
PS1149 - 28. Physical exercise increases NO and HDL production, both of
PS1150 - which increase EPC recruitment and EPC levels (159-161).
PS1151 - --------------------------------------------------------
PS1152 - Despite the mounting evidence implicating progenitor cell
PS1153 - involvement in the regression of atherosclerosis, there are
PS1154 - concerns and caution has been advised. Bone marrow-derived
PS1155 - progenitor cells have been associated with
PS1156 - neovascularization and vessel remodelling, which can cause
PS1157 - plaque destabilization (130,162). In addition, EPCs that
PS1158 - have the osteoblast marker osteocalcin are retained within
PS1159 - the lesion for endothelial repair, but are also believed to
PS1160 - lead to the induction and progression of coronary
PS1161 - calcification rather than normal endothelial repair (163).
PS1163 - ..
PS1164 - This seems to offer a path for folks to treat atherosclerosis by
PS1165 - elevating HDL and EPCs that regress plaque, that complements
PS1166 - medications that lower LDL, which slows advance of plaque.
PS1168 - ..
PS1169 - Artile continues...
PS1170 -
PS1171 - 29. EC apoptosis, migration and proliferation
PS1173 - ..
PS1174 - As atherosclerosis persists, ECs become apoptotic, leading
PS1175 - to the denudation of the vessel wall. Apoptosis is known to
PS1176 - be initiated by the activation of the death receptor and
PS1177 - mitochondrial-mediated apoptotic pathways.
PS1179 - ..
PS1180 - HDL may have a role in preventing EC apoptosis and
PS1181 - promoting endothelial repair (164). HDL can directly or
PS1182 - indirectly inhibit endothelial apoptosis either by
PS1183 - decreasing the levels of TNF-?, oxidized LDL and growth
PS1184 - factors, or by inhibiting apoptotic pathways. These
PS1185 - anti-apoptotic properties are mediated by constituents
PS1186 - within HDL. ApoA1, an important protein of the RCT
PS1187 - pathways, diminishes oxidized LDL and TNF-? induced
PS1188 - apoptosis (164?166). Lysosphingolipids within HDL, such as
PS1189 - sphingosylphonphorylcholine and lysosulfatide, can inhibit
PS1190 - growth factor-induced apoptosis as well as directly
PS1191 - interfere with apoptotic signalling within ECs by
PS1192 - activating the Akt signalling pathways (167?169).
PS1194 - ..
PS1195 - 30. Endothelial migration and proliferation is also promoted by HDL.
PS1196 -
PS1197 - Endothelial migration is believed to be stimulated by
PS1198 - the interaction between SR-BI and HDL (157).
PS1199 - Alternatively, sphingosine-1-phosphate within HDL can
PS1200 - induce endothelial cell migration by activating
PS1201 - Ras/Raf1-dependent ERK (157,167). The induction of EC
PS1202 - proliferation by HDL is mediated by downregulating
PS1203 - ADAMTS-1, by activating the protein kinase C pathway and by
PS1204 - increasing intracellular Ca2+ levels through phospholipase
PS1205 - C activation (170?172).
PS1207 - ..
PS1208 - 31. SMOOTH MUSCLE CELL PROLIFERATION AND REGRESSION
PS1209 -
PS1210 - Although there are four known smooth muscle cell
PS1211 - subpopulations (173?175), focus has been placed on
PS1212 - understanding two morphologically distinct subpopulations.
PS1213 - The majority of vascular smooth muscle cells (VSMCs)
PS1214 - normally found in the arterial media are elongated and
PS1215 - spindle shaped, forming the classic "hills and valley"
PS1216 - growth pattern. These "swirling-type" VSMCs have a
PS1217 - contractile phenotype. VSMCs with the synthetic phenotype,
PS1218 - also known as the "epithelioid-type", are only present in
PS1219 - small proportions within the arterial media. The synthetic
PS1220 - phenotype of VSMC is cuboidal in shape and displays a
PS1221 - cobblestone appearance at confluence. These VSMCs are
PS1222 - believed to be the major VSMC contributor to
PS1223 - atherosclerotic plaque progression (176?178). Akin to
PS1224 - macrophages, accumulation of intercellular lipids can
PS1225 - change VSMCs into foam cells, which may be considered a
PS1226 - third important phenotype of VSMC found in atherosclerotic
PS1227 - plaques. Moreover, de-differentiation of VSMC decreases
PS1228 - its affinity to HDL, thus effectively decreasing
PS1229 - apo-mediated cholesterol efflux and contributing to the
PS1230 - early events of foam cell transformation (179).
PS1232 - ..
PS1233 - 32. Despite the large amount of evidence linking VSMC to
PS1234 - atherosclerotic plaque progression, little is known about
PS1235 - their involvement in atherosclerotic plaque regression.
PS1236 - Nevertheless, regression can be induced by the removal of
PS1237 - lipids from sterol-loaded VSMC and by the cessation of VSMC
PS1238 - proliferation, which is accompanied by the reversal of the
PS1239 - pathological phenotypic modulation. Sterol unloading from
PS1240 - VSMCs shares many similarities with macrophage sterol
PS1241 - removal. SR-BI, a mediator of cholesterol efflux in
PS1242 - macrophage and influx in hepatocytes are also expressed in
PS1243 - VSMCs (180). Although synthetic VSMCs have a reduced
PS1244 - affinity for NO, NO is still capable of inhibiting smooth
PS1245 - muscle cell proliferation under cell culture conditions.
PS1246 - Supplementation with L-arginine, the precursor of NO, has
PS1247 - also been shown to induce plaque regression in
PS1248 - cholesterol-fed rabbits (181). Bioactive fatty acids such
PS1249 - as prostacyclin I1 and prostaglandin E2 maintain the
PS1250 - contractile phenotype of VSMCs and play a major role in
PS1251 - reducing migration and proliferation of VSMCs through
PS1252 - activation of peroxisome proliferator-activated receptors
PS1253 - (PPARs). Activation of both PPAR-? and PPAR-? leads to the
PS1254 - suppression of proinflammatory cytokines by inhibiting the
PS1255 - activity of NF-?B (182,183). In addition, PPAR-? inhibits
PS1256 - proliferation through a p16/pRb/E2F-mediated suppression of
PS1257 - telomerase activity. PPAR-? activity inhibits VSMC
PS1258 - migration and proliferation by blocking the cell cycle
PS1259 - (184?186). PPAR activation regulates lipid metabolism and
PS1260 - inhibits foam cell formation by augmenting the expression
PS1261 - of scavenger receptors (187).
PS1263 - ..
PS1264 - 33. CONCLUSION
PS1265 -
PS1266 - Nearly a half century ago, atherosclerotic plaque
PS1267 - regression was considered to be an unachievable feat. Now
PS1268 - it is recognized that established plaques can rapidly
PS1269 - stabilize and regress in animals and humans. Experimental
PS1270 - data have shown that plaque regression is not simply a
PS1271 - rewinding of the sequences of events that lead to lesion
PS1272 - progression, but instead involves specific cellular and
PS1273 - molecular pathways that are eventually able to mobilize all
PS1274 - pathological components of the plaque. HDL, ECs and VSMCs
PS1275 - all play important roles in the progression and regression
PS1276 - of atherosclerosis. Targeting of these cells and molecules
PS1277 - in the future will ensure pharmaceutical agents are able to
PS1278 - elicit even better plaque regression.
PS1280 - ..
PS1281 - [On 151019 0930 Radiology report on CCTA performed on
PS1282 - 151019, indicates calcification in original bypassed
PS1283 - arteries has increased since CABG +4 surgery on 091022;
PS1284 - and further than bypass grafts are clear of plaque -
PS1285 - aligns with this research theorizing atherosclerosis
PS1286 - plaques regress rapidly with elevated HDL and EPCs.
PS1287 - ref SDS 73 J14N
PS1289 - ..
PS1290 - [On 151019 0930 an undated addendum was added to report
PS1291 - on CCTA test on 151019, that clarifies findings and
PS1292 - impressions by establishing CCTA found no evidence of
PS1293 - plaque, stenosis, occlusion of any kind or amount after
PS1294 - raising HDL 30 on 091022, when CABG x4 was performed,
PS1295 - and after hiking 11,000 miles beginning in 2011 that
PS1296 - raised HDL 73 on 160203. ref SDS 73 SU4L
PS1298 - ..
PS1299 - [On 160405 1305 Evacetrapib raised HDL 130% failed
PS1300 - clinical trial Eli Lilly cholesterol drug CEPT inhibitor
PS1301 - did not reduce CV events; raised blood pressure
PS1302 - (hypertension), ref SDS 79 AF51 Doctors discouraged
PS1303 - Merck anacetrapib and Amgen TA-8995 which raise HDL
PS1304 - similarly, expect fail to improve clinical outcomes.
PS1305 - ref SDS 79 OH42
PS1307 - ..
PS1308 - [On 160424 1144 telomere length protective ends of
PS1309 - chromosomes age biomarker, ref SDS 82 EU3O Telomere
PS1310 - length relatively stable until age 70, ref SDS 82 HQ61,
PS1312 - ..
PS1313 - [On 180111 1143 further research on telomeres indicates
PS1314 - aerobic exercise maintains and can increase telomeres.
PS1315 - ref SDS 86 MN6N Another article reports benefits of
PS1316 - aerobic exercise to maintain telomeres. ref SDS 86 0Z6K
PS1318 - ..
PS1319 - [On 200124 0705 IVUS found completely clear (stenosis 0)
PS1320 - 11 years after CABG x4 and after raising HDL 30 at time
PS1321 - of CABG, to HDL 83 on 181112, demonstrates method and
PS1322 - results raising HDL > 60. ref SDS 87 ME8G
PS1324 - ..
PS1325 - [On 230919 1230 Doctor Iannuzzi vascular surgeon
PS1326 - comments on CT saying..."aorta measures 2.6 cm. The
PS1327 - plaque irregularity has progressed compared to 2009,
PS1328 - although has been stable over the past 2 years"... while
PS1329 - patient hiking 15 - 30 miles per day and HDL 55 - 65,
PS1330 - with EPCs assumed comparably elevated. ref SDS 88 GP3I
PS1331 -
PS1332 -
PS1333 -
PS1334 -
PS14 -
SUBJECTS
Default Null Subject Account for Blank Record
PT03 -
PT0401 - ..
PT0402 - HDL Lowered by Inflammation Affecting Liver Function
PT0403 - Inflammation Lowers HDL by Affecting Liver Function
PT0404 -
PT0405 - During telephone meeting on 210415 0900, ref SDS 85 SX4N, Doctor
PT0406 - Grunfeld related paper published with Doctor Feingold...
PT0407 -
PT0408 - NIH - National Institute of Health
PT0409 - National Center for Biotechnology Information
PT0410 - National Library of Medicine
PT0412 - ..
PT0413 - The Effect of Inflammation and Infection on Lipids and Lipoproteins
PT0414 -
PT0415 -
PT0416 - https://www.ncbi.nlm.nih.gov/books/NBK326741/#:~:text=Decreased%20HDL%20Levels,triglycerides%2C%20and%20free%20fatty%20acids
PT0417 -
PT0418 - Kenneth R. Feingold, MD and Carl Grunfeld, MD, PhD
PT0420 - ..
PT0421 - Chronic inflammatory diseases, such as rheumatoid arthritis,
PT0422 - systemic lupus erythematosus, and psoriasis and infections,
PT0423 - such as periodontal disease and HIV, are associated with an
PT0424 - increased risk of cardiovascular disease. Patients with these
PT0425 - disorders also have an increase in coronary artery calcium
PT0426 - measured by CT and carotid intima media thickness measured by
PT0427 - ultrasound. Inflammation and infections induce a variety of
PT0428 - alterations in lipid metabolism that may initially dampen
PT0429 - inflammation or fight infection, but if chronic could
PT0430 - contribute to the increased risk of atherosclerosis. The most
PT0431 - common changes are decreases in serum HDL and increases in
PT0432 - triglycerides.
PT0433 -
PT0435 - ..
PT0436 - Not clear that inflammation from extended exercise, e.g.,
PT0437 - matatarsalgia, blisters, calluses, etc., or knees, hips, etc., has
PT0438 - negative impact of liver producing HDL, as discussed in this article,
PT0439 - citing inflammation that occurs with Rheumatoid Arthritis, Systemic
PT0440 - Lupus Erythematosus, Psoriasis.
PT0442 - ..
PT0443 - On 200221 0800 during meeting in Orthopedics, Doctor Thuillier advised
PT0444 - that PRP treatments injecting concentrated platelets into feet and
PT0445 - knee injuries not only generates collagen that heals wounds to prevent
PT0446 - pain, so that hiking can occur, the concentrated platelets also
PT0447 - prevent inflammation that occurs with painful injuries, which
PT0448 - otherwise blocks the liver from producing HDL. ref SDS 83 WY8H
PT0449 -
PT0450 -
PT0452 - ..
PT0453 -
PT05 -
SUBJECTS
Naproxen NSAID AI Research Reduce Inflammation Hiking Injuries Feet
Q403 -
Q40401 - ..
Q40402 - AI Research Inflammation Reduced by Naproxen Enables HDL to Rise
Q40403 - Inflammation Naproxen NSAID Manages Both Pain and Inflammation So HDL Can Increase
Q40404 - Naproxen NSAID Manages Pain and Inflammation So HDL Can Rise
Q40405 - NSAID Naproxen Manages Pain and Inflammation So HDL Can Rise
Q40406 -
Q40407 - Research on 240411, using Microsoft AI system...
Q40408 -
Q40409 - Several years experience showing Naproxen during hiking enabled
Q40410 - HDL to rise 10 points over a week. This was in 2018. In
Q40411 - recent weeks taking Tramadol to manage pain, which does not
Q40412 - control inflammation, HDL dropped 10 points. The past 5 days,
Q40413 - switched back to Naproxen, to test if better control of
Q40414 - inflammation will enable HDL to rise back. Just had a blood
Q40415 - draw, so will see what happens with results later today or
Q40416 - tomorrow. Experience indicates inflammation is a major factor
Q40417 - with HDL.
Q40419 - ..
Q40420 - Microsoft Copilot
Q40422 - ..
Q40423 - Thank you for sharing your personal experience! It's
Q40424 - fascinating how our bodies respond to different medications
Q40425 - and lifestyle changes. Let?s delve into this further:
Q40427 - ..
Q40428 - Naproxen and HDL:
Q40429 -
Q40430 - Your observation that taking Naproxen during hiking led to
Q40431 - a 10-point increase in HDL cholesterol over a week aligns
Q40432 - with the known anti-inflammatory properties of this
Q40433 - medication.
Q40435 - ..
Q40436 - Naproxen is an NSAID that helps reduce inflammation, which
Q40437 - can positively impact cholesterol levels.
Q40439 - ..
Q40440 - Tramadol and HDL:
Q40441 -
Q40442 - Tramadol, on the other hand, is an opioid pain medication.
Q40443 - Unlike Naproxen, it doesn?t directly address inflammation.
Q40445 - ..
Q40446 - The drop in HDL cholesterol while taking Tramadol could be
Q40447 - due to its different mechanism of action.
Q40449 - ..
Q40450 - Inflammation and Cholesterol:
Q40451 -
Q40452 - Inflammation plays a crucial role in cardiovascular health.
Q40454 - ..
Q40455 - Chronic inflammation can lead to changes in lipid
Q40456 - metabolism, affecting both HDL and LDL (low-density
Q40457 - lipoprotein) cholesterol levels.
Q40459 - ..
Q40460 - By managing inflammation, you may indeed see improvements
Q40461 - in HDL cholesterol.
Q40463 - ..
Q40464 - Monitoring and Results:
Q40465 -
Q40466 - It?s excellent that you?ve recently switched back to
Q40467 - Naproxen to test its impact on HDL levels.
Q40469 - ..
Q40470 - The blood draw results will provide valuable insights into
Q40471 - whether better inflammation control positively affects your
Q40472 - HDL cholesterol.
Q40474 - ..
Q40475 - Holistic Approach:
Q40476 -
Q40477 - Remember that lifestyle factors also influence HDL levels:
Q40479 - ..
Q40480 - Regular exercise, including hiking, can raise HDL
Q40481 - cholesterol.
Q40483 - ..
Q40484 - A heart-healthy diet rich in fruits, vegetables, whole
Q40485 - grains, and healthy fats contributes to overall lipid
Q40486 - balance.
Q40488 - ..
Q40489 - Avoiding smoking and moderating alcohol intake are
Q40490 - essential.
Q40492 - ..
Q40493 - Consult Your Healthcare Provider:
Q40494 -
Q40495 - Continue to work closely with your healthcare provider.
Q40497 - ..
Q40498 - They can guide you based on your specific health profile
Q40499 - and recommend the best approach to manage pain,
Q40500 - inflammation, and cholesterol.
Q40501 -
Q40502 -
Q40503 -
Q40504 -
Q40505 -
Q40506 -
Q40507 -
Q40508 -
Q406 -
SUBJECTS
Default Null Subject Account for Blank Record
Q503 -
Q50401 - ..
Q50402 - Liver Damage Disease Lowers HDL Caused by Atrial Fibrillation AF AFL PAF
Q50403 - Atrial Fibrillation AF AFL PAF Damages Liver Disease Lowers HDL
Q50404 - HDL Lowered by Atrial Fibrillation Damages Liver Function
Q50405 -
Q50406 -
Q50407 - Mayo Clinic
Q50408 - Liver Disease
Q50410 - ..
Q50411 - The liver is an organ about the size of a football. It sits
Q50412 - just under your rib cage on the right side of your abdomen.
Q50413 - The liver is essential for digesting food and ridding your
Q50414 - body of toxic substances
Q50415 -
Q50416 - https://www.mayoclinic.org/diseases-conditions/liver-problems/symptoms-causes/syc-20374502
Q50418 - ..
Q50419 - Over time, conditions that damage the liver can lead to
Q50420 - scarring (cirrhosis), which can lead to liver failure, a
Q50421 - life-threatening condition. But early treatment may give the
Q50422 - liver time to heal.
Q50424 - ..
Q50425 - Liver Disease Symptoms
Q50426 -
Q50427 - Skin and eyes that appear yellowish (jaundice)
Q50428 - Abdominal pain and swelling
Q50429 - Swelling in the legs and ankles
Q50430 - Itchy skin
Q50431 - Dark urine color
Q50432 - Pale stool color
Q50433 - Chronic fatigue
Q50434 - Nausea or vomiting
Q50435 - Loss of appetite
Q50436 - Weight loss
Q50437 - Tendency to bruise easily
Q50438 - fluid collection in the abdomen, known as ascites
Q50439 -
Q50440 -
Q50441 -
Q50443 - ..
Q50444 - Liver Damage Blood Tests
Q50445 - Blood Tests Liver Damage
Q50446 -
Q50447 - Journal of Heptatology
Q50448 -
Q50449 - HDL-related biomarkers are robust predictors of survival in
Q50450 - patients with chronic liver failure
Q50451 -
Q50452 - https://www.journal-of-hepatology.eu/article/S0168-8278(20)30073-8/fulltext#:~:text=People%20who%20suffer%20from%20cirrhosis,problem%20in%20severe%20liver%20disease.
Q50454 - ..
Q50455 - High-density lipoprotein cholesterol (HDL-C) levels are
Q50456 - reduced in patients with chronic liver disease and inversely
Q50457 - correlate with disease severity. During acute conditions such
Q50458 - as sepsis, HDL-C levels decrease rapidly and HDL particles
Q50459 - undergo profound changes in their composition and function.
Q50460 -
Q50462 - ..
Q50463 - Healthline
Q50464 - Liver Function Tests
Q50465 -
Q50466 -
Q50467 - https://www.healthline.com/health/liver-function-tests
Q50468 -
Q50469 - Alanine transaminase (ALT)
Q50470 - ALT Alanine transaminase
Q50472 - ..
Q50473 - Alanine transaminase (ALT) is used by your body to metabolize
Q50474 - protein. If the liver is damaged or not functioning properly,
Q50475 - ALT can be released into the blood. This causes ALT levels to
Q50476 - increase. A higher result than what?s typical on this test can
Q50477 - be a sign of liver damage.
Q50479 - ..
Q50480 - It?s estimated that about 10 percent of people in the United
Q50481 - States have elevated ALT levels.
Q50482 -
Q50484 - ..
Q50485 - Aspartate aminotransferase (AST)
Q50486 - AST Aspartate aminotransferase
Q50488 - ..
Q50489 - When the liver is damaged, AST can be released into the
Q50490 - bloodstream. A high result on an AST test might indicate a
Q50491 - problem with the liver or muscles.
Q50493 - ..
Q50494 - Since AST levels aren?t as specific of a marker for liver
Q50495 - damage as ALT, it?s usually measured together with ALT to
Q50496 - check for liver problems. For example, a high AST:ALT ratio
Q50497 - may indicate alcoholic liver diseaseTrusted Source.
Q50498 -
Q50500 - ..
Q50501 - Alkaline phosphatase (ALP)
Q50502 -
Q50504 - ..
Q50505 - Albumin test
Q50507 - ..
Q50508 - Albumin is the main protein made by your liver. It performs
Q50509 - many important bodily functions.
Q50511 - ..
Q50512 - For example, albumin nourishes your tissues and transports
Q50513 - hormones, vitamins, and other substances throughout your body.
Q50514 - An albumin test measures how well your liver is making this
Q50515 - particular protein.
Q50516 -
Q50518 - ..
Q50519 - Bilirubin test
Q50521 - ..
Q50522 - Bilirubin is a waste product from the breakdown of red blood
Q50523 - cells. It?s ordinarily processed by the liver. It passes
Q50524 - through the liver before being excreted through your stool.
Q50526 - ..
Q50527 - A damaged liver can?t properly process bilirubin. This leads to
Q50528 - an atypically high level of bilirubin in the blood. Certain
Q50529 - inherited diseases can raise bilirubin levels, even when liver
Q50530 - function works as expected.
Q50531 -
Q50532 -
Q50534 - ..
Q50535 - Liver Damage Radiology Image Tests
Q50536 - Image Liver Damage Tests Radiology
Q50537 - Radiology Liver Damage Tests Image
Q50538 -
Q50539 -
Q50540 - https://www.webmd.com/digestive-disorders/tests-for-cirrhosis
Q50541 -
Q50542 - CT scan. Using X-rays and a computer, it makes detailed
Q50543 - pictures of your liver. You might get a contrast dye before
Q50544 - the test to help your doctor see your liver more clearly.
Q50546 - ..
Q50547 - MRI This uses powerful magnets and radio waves to make pictures
Q50548 - of your liver. You might get contrast dye before the test.
Q50550 - ..
Q50551 - Ultrasound. It uses sound waves to make pictures of your liver.
Q50553 - ..
Q50554 - Endoscopy. It uses a flexible tube with a light and camera on
Q50555 - one end. It can be used to look for abnormal blood vessels
Q50556 - called varices. These form when cirrhosis scars block blood
Q50557 - flow in the portal vein that carries blood to your liver. Over
Q50558 - time, pressure builds up in this vein. Blood backs up into
Q50559 - blood vessels in the stomach, intestines, or esophagus.
Q50561 - ..
Q50562 - Magnetic resonance elastography and transient elastography.
Q50563 - These newer tests look for stiffness in your liver caused by
Q50564 - cirrhosis scars. Your doctor might use them instead of a liver
Q50565 - biopsy, because they're less invasive. But they?re not yet
Q50566 - widely available.
Q50568 - ..
Q50569 - Liver Biopsy
Q50571 - ..
Q50572 - During this procedure, your doctor first numbs the skin on
Q50573 - your belly over your liver. Then, they place a thin needle
Q50574 - through your belly into your liver and removes a small piece
Q50575 - of tissue. They might use a CT scan, ultrasound, or other
Q50576 - imaging method to guide the needle.
Q50578 - ..
Q50579 - The tissue sample goes to a lab. A lab tech looks at it under
Q50580 - a microscope for signs of damage. A biopsy can diagnose
Q50581 - cirrhosis and help your doctor learn the cause.
Q50582 -
Q50584 - ..
Q50585 - Atril Fibrillation Causes Liver Damage Lowers HDL
Q50586 - Liver Damage Caused by Atril Fibrillation Lowers HDL
Q50587 -
Q50588 -
Q50589 - Therapeutic Advances
Q50590 - Gasteronenterology
Q50592 - ..
Q50593 - After AF was diagnosed, research found reports of studies assocating
Q50594 - AF with lowering HDL, reported on 200103 0700. ref SDS 81 MZ37
Q50595 -
Q50597 - ..
Q50598 - Gastrointestinal and liver diseases and atrial fibrillation:
Q50599 - a review of the literature
Q50600 - ------------------------------------------------------------
Q50601 -
Q50602 - AF Patients Treated wtih Apixaban Could Get Liver Damage
Q50603 - Apixaban Could Cause Liver Damage for Patients with Afib
Q50605 - ..
Q50606 - Anticoagulation and liver injury
Q50607 -
Q50608 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448121/
Q50610 - ..
Q50611 - Patients with AF on treatment with warfarin or DOACs are at
Q50612 - risk for liver injury, though the risk is relatively small.
Q50614 - ..
Q50615 - A study from a large US-based healthcare database identified
Q50616 - 960 hospitalizations for liver injury over 14 months of follow
Q50617 - up (7.3 events per 1000 person-years) among patients with
Q50618 - nonvalvular AF treated with DOACs.
Q50620 - ..
Q50621 - The risk of liver injury was lowest for patients treated with
Q50622 - dabigatran and highest for those treated with warfarin,
Q50623 - whereas rivaroxaban and apixaban users had intermediate risk.
Q50625 - ..
Q50626 - Though liver injury is a relatively rare complication,
Q50627 - clinicians and patients should consider risk factors for liver
Q50628 - injury when choosing a specific oral anticoagulant.
Q50629 -
Q50630 -
Q50632 - ..
Q50633 - Metoprolol-induced Severe Liver Injury and Successful
Q50634 - Management with Therapeutic Plasma Exchange
Q50635 -
Q50636 -
Q50637 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453740/
Q50639 - ..
Q50640 - Metoprolol has been linked to only rare cases of drug-induced
Q50641 - liver injury,
Q50642 -
Q50643 -
Q50644 -
Q50645 -
Q50646 -
Q50647 -
Q50648 -
Q50649 -
Q50650 -
Q50651 -
Q50652 -
Q50654 - ..
Q50655 - Liver Damage Reversible Early Stages
Q50656 - Cirrhosis Severe Liver Disease Scar Tissue Difficult to Reverse
Q50657 -
Q50658 - University of Iowa Hospitals & Clinics
Q50659 -
Q50660 - https://uihc.org/health-topics/liver-disease-frequently-asked-questions
Q50662 - ..
Q50663 - Can liver damage be reversed?
Q50665 - ..
Q50666 - The liver is a unique organ. It is the only organ in the body
Q50667 - that is able to regenerate. With most organs, such as the
Q50668 - heart, the damaged tissue is replaced with scar, like on the
Q50669 - skin. The liver, however, is able to replace damaged tissue
Q50670 - with new cells. If up to 50 to 60 percent of the liver cells
Q50671 - may be killed within three to four days in an extreme case
Q50672 - like a Tylenol overdose, the liver will repair completely
Q50673 - after 30 days if no complications arise.
Q50675 - ..
Q50676 - Complications of liver disease occur when regeneration is
Q50677 - either incomplete or prevented by progressive development of
Q50678 - scar tissue within the liver. This occurs when the damaging
Q50679 - agent such as a virus, a drug, alcohol, etc., continues to
Q50680 - attack the liver and prevents complete regeneration. Once scar
Q50681 - tissue has developed it is very difficult to reverse that
Q50682 - process. Severe scarring of the liver is the condition known
Q50683 - as cirrhosis. The development of cirrhosis indicates late
Q50684 - stage liver disease and is usually followed by the onset of
Q50685 - complications.
Q50686 -
Q50687 -
Q50688 -
Q50689 -
Q50690 -
Q50691 -
Q50692 -
Q50693 -
Q507 -
SUBJECTS
Default Null Subject Account for Blank Record
Q603 -
Q60401 - ..
Q60402 - HDL Controversy Drug Induced Fails Regress Atherosclerosis Plaque
Q60403 - Controversy HDL Drug Induced Fails Regress Atherosclerosis Plaque
Q60404 -
Q60405 -
Q60406 - Medscape Cardiology
Q60407 -
Q60408 - Medscape Medical News from the:
Q60409 - European Society of Cardiology (ESC) Congress 2013
Q60411 - ..
Q60412 - Raising HDL Cholesterol: The Controversy
Q60413 -
Q60414 - Robert Harrington, MD; Renu Virmani, MD; Stephen Nicholls,
Q60415 - MBBS, PhD
Q60416 -
Q60417 - https://www.medscape.com/viewarticle/812543
Q60419 - ..
Q60420 - Date........................... October 16, 2013
Q60421 -
Q60422 -
Q60423 - 1. Introductions
Q60424 -
Q60425 - Robert Harrington, MD: Hi. I'm Bob Harrington from Stanford
Q60426 - University. I'm here at the European Society of Cardiology
Q60427 - (ESC) meetings in Amsterdam and have had an opportunity to
Q60428 - talk with a few colleagues about some of the hot, breaking
Q60429 - science at these meetings. Joining me today is Renu Virmani,
Q60430 - pathologist from Washington, DC. Welcome, Renu.
Q60432 - ..
Q60433 - Renu Virmani, MD: Thank you.
Q60435 - ..
Q60436 - Dr Harrington: And Steve Nicholls, cardiologist from
Q60437 - Adelaide, Australia, also joining us.
Q60439 - ..
Q60440 - Stephen Nicholls, MBBS, PhD: Thank you.
Q60442 - ..
Q60443 - Dr Harrington: Now, we are having this discussion because
Q60444 - while we were sitting out there in the lunch room, there
Q60445 - was a bit of argument going around about whether raising
Q60446 - HDL is going to help our patients.
Q60448 - ..
Q60449 - You presented a trial this morning, Steve, about inducing
Q60450 - ApoA. There are a number of phase 2-type trials going on
Q60451 - with direct infusion of ApoA1 or the prime constituent
Q60452 - protein of HDL. None of it has looked good so far, and
Q60453 - that is where the context of the argument would be.
Q60455 - ..
Q60456 - 2. Biologics of Plaque
Q60457 -
Q60458 - Dr Harrington: So, Renu, I will ask you first. You are
Q60459 - skeptical that giving people back HDL is going to help
Q60460 - from a cardiovascular perspective.
Q60462 - ..
Q60463 - Dr Virmani: For me, what really matters is in the
Q60464 - arterial wall, the lipid that gets in.
Q60466 - ..
Q60467 - Dr Harrington: Don't we think about ApoA as a
Q60468 - molecule that can suck out LDL from the
Q60469 - plaque? I am an interventional cardiologist. I
Q60470 - like the visual of sucking out the plaque.
Q60472 - ..
Q60473 - Dr Virmani: I think it sounds attractive. In vitro you can
Q60474 - do macrophages and you can see it suck out, but macrophages
Q60475 - have to travel to that necrotic core to be able to suck
Q60476 - out. And, you know, that surface is very rich in type 1
Q60477 - collagen; to break that is not that easy. I'm not convinced
Q60478 - that we can get macrophages there, pick it out, and then
Q60479 - take it back into the circulation.
Q60481 - ..
Q60482 - Dr Harrington: Interesting hypothesis, but you believe
Q60483 - there might be biologic mechanisms that prevent it from
Q60484 - working?
Q60486 - ..
Q60487 - Dr Virmani: Absolutely. I think biologics of the plaque
Q60488 - itself prevent it.
Q60490 - ..
Q60491 - 3. Why HDL?
Q60493 - ..
Q60494 - Dr Harrington: Steve, you probably have a little bit of a
Q60495 - different perspective. Before you tell us where you think
Q60496 - the field is going, review for our audience what has been
Q60497 - studied so far -- mechanisms -- and what have been the
Q60498 - results.
Q60500 - ..
Q60501 - Dr Nicholls: We could ask ourselves why we are interested
Q60502 - in HDL in the first place.
Q60504 - ..
Q60505 - Dr Harrington: Let's start there.
Q60507 - ..
Q60508 - Dr Nicholls: The reality is that in large populations, if
Q60509 - you've got low levels of HDL cholesterol, you have got a
Q60510 - high risk. We know that in animal studies, if you do
Q60511 - something to HDL -- you infuse it, you turn on one of its
Q60512 - major proteins using transgenic studies -- favorable things
Q60513 - happen to plaque models of atherosclerosis. It has a range
Q60514 - of biological activities which, in theory, could have a
Q60515 - favorable effect on the arterial wall: lipid mobilization,
Q60516 - anti-inflammatory effects, antithrombotic effects. We
Q60517 - don't know which of them occur in vivo and whether that
Q60518 - will translate to a favorable effect. We have seen, if you
Q60519 - look at established medical therapies, that even small
Q60520 - increases in HDL cholesterol predict the benefits of the
Q60521 - fibrate studies when they worked. We have seen it
Q60522 - associate with the benefit of statins.
Q60524 - ..
Q60525 - 4. Infusing HDL
Q60526 -
Q60527 - Dr Nicholls: We have seen that if you infuse HDL, you
Q60528 - rapidly regress plaque. And so that tells me that if
Q60529 - you infuse it in large enough quantities, which don't
Q60530 - necessarily raise HDL cholesterol -- and that is the
Q60531 - big distinction here; the concerns with the failed
Q60532 - studies have been about HDL cholesterol-raising drugs,
Q60533 - and that may be different from targeting HDL -- and so
Q60534 - if you infuse HDL, give a boatload of it into the
Q60535 - plasma straight away, it seems to be doing the right
Q60536 - thing. It is shrinking plaques. Ultimately, the HDL
Q60537 - hypothesis will not be proven until an HDL drug
Q60538 - reduces cardiovascular events, and we haven't seen
Q60539 - that yet.
Q60541 - ..
Q60542 - [On 160405 1305 Evacetrapib raised HDL 130% failed
Q60543 - clinical trial Eli Lilly cholesterol drug CEPT inhibitor
Q60544 - did not reduce CV events; raised blood pressure
Q60545 - (hypertension), ref SDS 79 AF51 Doctors discouraged
Q60546 - Merck anacetrapib and Amgen TA-8995 which raise HDL
Q60547 - similarly, expect fail to improve clinical outcomes.
Q60548 - ref SDS 79 OH42
Q60550 - ..
Q60551 - Dr Harrington: We really need to see an HDL infusing
Q60552 - agent in a large enough outcome study to tell us
Q60553 - yay or nay.
Q60555 - ..
Q60556 - Dr Nicholls: To me, that is probably the purest
Q60557 - hypothesis. You know, if you look at the other drugs that
Q60558 - are out there, niacin has failed. Niacin does lots of
Q60559 - other things. The CETP inhibitors, some of them failed
Q60560 - already; they have got some baggage. There are 2 CETP
Q60561 - inhibitors that are very potent that are in phase 3. They
Q60562 - double HDL but they lower LDL 30% to 40%, so they may just
Q60563 - work just because of that. We looked at an ApoA1 inducer
Q60564 - here. It didn't work. It didn't have any incremental
Q60565 - effect on HDL and it didn't regress plaque any more than
Q60566 - placebo.
Q60568 - ..
Q60569 - Research indicates raising HDL alone is not enough to regress
Q60570 - atherosclerosis. At the same time, EPC counts must be increased, per
Q60571 - above. ref SDS 0 RA7K Research further indicates EPC counts can be
Q60572 - increased by extended endurance exercise, per above. ref SDS 0 6O9M
Q60574 - ..
Q60575 - [On 160405 1305 Evacetrapib raised HDL 130% failed
Q60576 - clinical trial Eli Lilly cholesterol drug CEPT inhibitor
Q60577 - did not reduce CV events; raised blood pressure
Q60578 - (hypertension), ref SDS 79 AF51 Doctors discouraged
Q60579 - Merck anacetrapib and Amgen TA-8995 which raise HDL
Q60580 - similarly, expect fail to improve clinical outcomes.
Q60581 - ref SDS 79 OH42
Q60583 - ..
Q60584 - Dr Harrington: Did it have any toxic effects?
Q60586 - ..
Q60587 - Dr Nicholls: It raised liver enzymes a bit so I think that
Q60588 - is a challenge. But that, again, doesn't become a test of
Q60589 - the HDL hypothesis because it didn't do anything above and
Q60590 - beyond therapy, so to me the purest test would be to infuse
Q60591 - it. We had some intriguing studies early with imaging they
Q60592 - had to reformulate -- all those companies.
Q60594 - ..
Q60595 - Dr Harrington: Are you talking about IVUS imaging?
Q60597 - ..
Q60598 - Dr Nicholls: In IVUS imaging, ultimately it is going to be
Q60599 - about events. That is what we care about for our patients,
Q60600 - and so we need better formulations. But we need them to
Q60601 - get to the clinical trials to evaluate them.
Q60603 - ..
Q60604 - 5. A Dead Hypothesis?
Q60605 -
Q60606 - Dr Harrington: Renu, let's go back to you and mechanism,
Q60607 - mechanism, mechanism.
Q60609 - ..
Q60610 - Dr Virmani: You know, it is very nice to say that animal
Q60611 - studies worked and the animal plaque resembled human plaque
Q60612 - -- absolutely not! It is very rich in macrophages and,
Q60613 - yes, you can convert, and not many necrotic cores.
Q60614 - Therefore, your animal studies are not appropriate.
Q60615 - Remember: We do it with very high cholesterols and
Q60616 - therefore we can reverse things in the animal. I think
Q60617 - human [disease] is a different disease which takes decades
Q60618 - to develop, and now you want to put a regression on it and
Q60619 - you are going to try and do it in a year or 2 years. I
Q60620 - just don't see how you are going to see it.
Q60622 - ..
Q60623 - Dr Nicholls: So we saw 3 imaging studies in humans, all
Q60624 - with an acute coronary syndrome within the preceding 2
Q60625 - weeks, weekly infusions of delipidated HDL on 4-6 occasions
Q60626 - over the next 2 months, rapid regression of disease.
Q60627 - Whether those therapies get to the clinic or not, it at
Q60628 - least supports the hypothesis, but until we have a drug
Q60629 - that targets HDL and it reduces cardiovascular morbidity
Q60630 - and mortality, we will not have proven the hypothesis.
Q60631 -
Q60632 - [On 160405 1305 Evacetrapib raised HDL 130% failed
Q60633 - clinical trial Eli Lilly cholesterol drug CEPT inhibitor
Q60634 - did not reduce CV events; raised blood pressure
Q60635 - (hypertension), ref SDS 79 AF51 Doctors discouraged
Q60636 - Merck anacetrapib and Amgen TA-8995 which raise HDL
Q60637 - similarly, expect fail to improve clinical outcomes.
Q60638 - ref SDS 79 OH42
Q60640 - ..
Q60641 - But I think the argument, that the hypothesis is dead on
Q60642 - the basis of the evidence we have seen, is a little
Q60643 - premature.
Q60645 - ..
Q60646 - Dr Harrington: Can I push here, Renu? Are you saying it
Q60647 - is dead or are you saying that there is still life here and
Q60648 - that Steve is making some points that have to be addressed?
Q60650 - ..
Q60651 - Dr Virmani: I think Steve is making some good points and I
Q60652 - think they have to be addressed. I totally agree that
Q60653 - infusion is going to be different as compared to what is
Q60654 - currently being done. I also think that imaging with IVUS
Q60655 - has its limitations, so you cannot rely on IVUS alone. We
Q60656 - have better tools today. Maybe we would be able to show
Q60657 - some regression if we can show, for example, that the area
Q60658 - of cholesterol becomes much less, or if we can show by
Q60659 - optical coherence tomographythat we start seeing fewer
Q60660 - macrophages -- that will be something that will be
Q60661 - encouraging, but I need that kind of encouragement.
Q60663 - ..
Q60664 - 6. PCKS9 Inhibitors
Q60666 - ..
Q60667 - Dr Nicholls: I think the other thing that we are in
Q60668 - complete agreement about is that cholesterol is important.
Q60669 - We have seen major advances by lowering LDL cholesterol.
Q60670 - We have now got these new drugs, which are now going into
Q60671 - phase 3 trials.
Q60673 - ..
Q60674 - Dr Harrington: Are you talking about the PCSK9
Q60675 - inhibitors?
Q60677 - ..
Q60678 - Dr Nicholls: PCSK9 inhibitors. They are going to lower
Q60679 - LDL another 50%, and it is just mind-boggling to think that
Q60680 - if you get an LDL of 30, what is going to happen there? So
Q60681 - there are 2 large outcome studies, and we have the good
Q60682 - fortune to be able to do an IVUS study in parallel and ask
Q60683 - whether we will see more regression than we have seen in
Q60684 - the studies where we have been able to get LDLs to 60. We
Q60685 - have to do the studies.
Q60687 - ..
Q60688 - Dr Harrington: The PCSK9 story is an interesting one,
Q60689 - isn't it, because it is all based on this hypothesis where
Q60690 - events decrease as LDL decreases, and what we don't know,
Q60691 - as you know well, is whether that curve plateaus.
Q60693 - ..
Q60694 - 7. Modifiable Risk
Q60695 -
Q60696 - Dr Nicholls: We talk a lot about residual risk, and I
Q60697 - think we really need to change the whole topic to
Q60698 - modifiable risk. The question is, at what point on that
Q60699 - line do we stop being able to modify the risk? We just
Q60700 - don't know that.
Q60702 - ..
Q60703 - Dr Harrington: But with these new studies, as you say, it
Q60704 - is the data that has been presented thus far at these
Q60705 - meetings, at AHA, at ACC. It is extraordinary, the effect
Q60706 - on lipids that these agents have.
Q60708 - ..
Q60709 - Dr Nicholls: Yes.
Q60711 - ..
Q60712 - Dr Virmani: If you look at IVUS studies, I think it is
Q60713 - interesting that with statins they can show very nicely
Q60714 - that calcium goes up. Now, once you have high calcium, are
Q60715 - you going to be able to show a further benefit? That is
Q60716 - going to be the problem with these.
Q60718 - ..
Q60719 - Dr Nicholls: We looked at that data a number of years ago
Q60720 - and looked at people according to how much calcium they
Q60721 - had. If you had a lot of calcium, you didn't progress and
Q60722 - you didn't regress.
Q60724 - ..
Q60725 - Dr Virmani: Yes.
Q60727 - ..
Q60728 - Dr Nicholls: They had a modifiable disease. They have
Q60729 - stable plaque.
Q60731 - ..
Q60732 - Dr Virmani: That is why stable plaque, I believe, should
Q60733 - not be treated percutaneously.
Q60735 - ..
Q60736 - Dr Harrington: That may be a hypothesis that we choose to
Q60737 - test, and that is an interesting question.
Q60739 - ..
Q60740 - Dr Nicholls: One of the questions that will come with all
Q60741 - of these imaging advances is, ultimately, how we are going
Q60742 - to use it in clinical practice and whether this is exactly
Q60743 - the right way to use it. Can we use it as a biomarker that
Q60744 - says that this person has got modifiable risk and this
Q60745 - person doesn't, and so we should be more aggressive with
Q60746 - that person?
Q60748 - ..
Q60749 - [on 140519 Doctor Feingold and Doctor Alba represented
Q60750 - that CCTA is not effective for evaluating regression of
Q60751 - atherosclerosis plaques as a result of raising HDL 100%
Q60752 - from HDL 30 to HDL 61, by hiking 11 miles per day for
Q60753 - several months, because CABG x4 patients have
Q60754 - established CVD that can only be treated with statin
Q60755 - medications, and (2) CABG surgery changes internal
Q60756 - anatomy into complexity that cannot be evaluated by CCTA
Q60757 - radiology technology, ref SDS 66 J83H, also set out in
Q60758 - VA Progress Notes. ref SDS 66 OW49
Q60759 -
Q60760 -
Q60761 -
Q60763 - ..
Q60764 - HDL-P Supplements HDL-C Measure Protection Against CVD Regress Atherosclerotic Plaque
Q60765 -
Q60766 - Article reports HDL-P Normal 32 - 34, supplements standard labs
Q60767 - measuring HDL-C normal range 35 - 45.
Q60768 -
Q60769 - Clinical Chemestry
Q60770 - Expert Insights in
Q60771 - Clinical Laboratory Medicine
Q60773 - ..
Q60774 - HDL-C vs HDL-P: How Changing One Letter Could Make a Difference in
Q60775 - Understanding the Role of High-Density Lipoprotein in Disease
Q60777 - ..
Q60778 - W. Sean Davidson
Q60779 - DOI: 10.1373/clinchem.2014.232769 Published October 2014
Q60780 -
Q60781 - http://clinchem.aaccjnls.org/content/60/11/e1
Q60782 -
Q60784 - ..
Q60785 - Before about 2006, most papers focusing on high-density
Q60786 - lipoprotein (HDL)2 contained an introductory sentence that
Q60787 - touted its protective role against cardiovascular disease
Q60788 - (CVD), usually via the reverse transport of cholesterol away
Q60789 - from the vessel wall. This was based on a mountain of
Q60790 - epidemiological evidence showing an inverse correlation between
Q60791 - plasma concentrations of HDL cholesterol (HDL-C) and CVD as
Q60792 - well as thousands of in vitro and animal model studies
Q60793 - demonstrating the cholesterol-carrying capacity of the
Q60794 - particles. More recently, however, confidence in a direct
Q60795 - atheroprotective role for HDL has wavered. HDL-targeted drugs
Q60796 - such as niacin and 2 different cholesteryl ester transfer
Q60797 - protein (CETP) inhibitors have failed in clinical trials,
Q60798 - despite raising HDL-C (nicely reviewed in (1)). Furthermore,
Q60799 - recent Mendelian randomization analyses suggest that genetic
Q60800 - anomalies that raise HDL-C fail to impart the CVD protections
Q60801 - predicted by epidemiologic findings (2). This has prompted
Q60802 - some to regard HDL as a marker or by product of other, more
Q60803 - directly atheroprotective, mechanisms. On the other hand,
Q60804 - large studies have shown that the cholesterol efflux capacity
Q60805 - of primarily HDL-containing [i.e., low-density lipoprotein
Q60806 - (LDL)-depleted] serum is a robust predictor of CVD, even better
Q60807 - than HDL-C (3), suggesting that HDL's mobilization of cellular
Q60808 - cholesterol may indeed be atheroprotective.
Q60810 - ..
Q60811 - Failure of drugs that elevate HDL 100, to lower incidence of CVD
Q60812 - deaths, is cited in articles above. ref SDS 0 8H3M
Q60814 - ..
Q60815 - Clinical trials that measure HDL-C 100 elevated by drug treatments,
Q60816 - what was HDL-P? Were Coronary CTA tests performed to evaluate
Q60817 - regression of atherosclerosis in the circulatory system?
Q60818 -
Q60819 - [On 160405 1305 Evacetrapib raised HDL 130% failed
Q60820 - clinical trial Eli Lilly cholesterol drug CEPT inhibitor
Q60821 - did not reduce CV events; raised blood pressure
Q60822 - (hypertension), ref SDS 79 AF51 Doctors discouraged
Q60823 - Merck anacetrapib and Amgen TA-8995 which raise HDL
Q60824 - similarly, expect fail to improve clinical outcomes.
Q60825 - ref SDS 79 OH42
Q60826 -
Q60828 - ..
Q60829 - So why has it been so difficult to determine whether HDL plays
Q60830 - a direct protective role in CVD? Some argue that the picture
Q60831 - has been clouded by the way HDL has been traditionally
Q60832 - quantified. The HDL-C measurement targets only a single HDL
Q60833 - component, and a relatively minor one at that: a maximum of 20%
Q60834 - of HDL mass is cholesterol or its ester. Ideally, one would
Q60835 - like to know the actual number of HDL particles (HDL-P)
Q60836 - circulating in plasma, not simply how much cholesterol they are
Q60837 - carrying. This is a relatively easy determination for LDL.
Q60838 - Because each particle contains a single copy of apolipoprotein
Q60839 - B (apoB), LDL-P is closely correlated with apoB concentrations.
Q60840 - HDL, on the other hand, can contain any combination of nearly
Q60841 - 90 different proteins (4), and although much of its protein
Q60842 - mass is composed of apoAI, there can be anywhere from 1 to 5
Q60843 - copies on a given particle. Furthermore, HDL lipid
Q60844 - compositions vary widely from a few percent up to 50% of
Q60845 - particle mass. Thus, HDL-C has an inherent bias toward the
Q60846 - larger, more cholesterol/lipid-rich particles and
Q60847 - underestimates smaller, lipid-poor forms. This is critical,
Q60848 - because recent evidence indicates that HDL is actually a
Q60849 - collection of numerous subspecies that play distinct functional
Q60850 - roles, not only in lipid homeostasis but also in inflammation,
Q60851 - innate immunity, and even glucose control. As an example,
Q60852 - pre-² forms of HDL contain relatively little lipid/cholesterol,
Q60853 - but excel in mobilizing cellular cholesterol via cell surface
Q60854 - transporters. HDL-P would include such particles, but HDL-C
Q60855 - likely does not.
Q60857 - ..
Q60858 - Up to now, there have been 2 primary methods for measuring
Q60859 - HDL-P. The most widely used relies on proton nuclear magnetic
Q60860 - resonance (NMR) (5). In NMR, lipid methyl groups emit
Q60861 - resonances that are unique to the chemical environments in
Q60862 - lipoprotein particles of different diameter, with the signal
Q60863 - intensity being proportional to their abundance. Therefore, the
Q60864 - analysis not only quantifies overall HDL-P, but also breaks
Q60865 - down the contribution of size subspeciessmall, medium, and
Q60866 - large HDL, for example. In a recent subanalysis of the
Q60867 - Multi-Ethnic Study of Atherosclerosis (MESA), the NMR-derived
Q60868 - HDL-P value outperformed HDL-C in predicting cardiovascular
Q60869 - risk (6). Importantly, this relationship held when LDL-P (also
Q60870 - measured by NMR) was factored into the analysis. In the
Q60871 - Justification for the Use of Statins in Prevention: an
Q60872 - Intervention Trial Evaluating Rosuvastatin (JUPITER),
Q60873 - NMR-derived HDL-P also showed a stronger association with CVD
Q60874 - than HDL-C or apoAI among subjects receiving the statin (7). A
Q60875 - second method for measuring HDL-P is based on ion mobility (IM)
Q60876 - spectrometry, where ionized lipoproteins are separated by size
Q60877 - and charge in a flow of inert gas subjected to modulated
Q60878 - electric fields (8). This approach was used to examine
Q60879 - subjects in the Malmö Diet and Cancer Study, revealing an
Q60880 - HDL-Passociated protection as well as a pattern of both LDL
Q60881 - and HDL subspecies that was associated with risk (9). These
Q60882 - studies highlight the potential of HDL-P measurement for
Q60883 - revealing new information about which types of particles, and
Q60884 - potentially which metabolic processes, are key players in the
Q60885 - protection from atherosclerosis.
Q60887 - ..
Q60888 - Despite the success of these HDL-P measurement strategies,
Q60889 - questions remain about their overall accuracy. The NMR method
Q60890 - routinely reports HDL-P concentrations to be in the range of
Q60891 - 32-34 ¼mol/L (7, 10) in normal individuals, whereas the IM
Q60892 - method reports 5-6 ¼mol/L (9, 11), a substantial disparity.
Q60893 - Both methods were initially validated by comparison to
Q60894 - biochemical determinations of HDL-C, apoAI, and HDL size by
Q60895 - nondenaturing gel electrophoresis of plasma samples (note: the
Q60896 - NMR deconvolution algorithm is proprietary, and it is not
Q60897 - explicitly clear from the literature how it was developed).
Q60898 - Although it is clear that the HDL-P abundance and size readouts
Q60899 - from both methods show strong correlations with these
Q60900 - parameters, the absolute accuracy (i.e., how well the HDL-P
Q60901 - value matches the true abundance of HDL particles in plasma) is
Q60902 - less well established. This is illustrated by examining the
Q60903 - stoichiometry of apoAI molecules per HDL particle determined by
Q60904 - each method. Given that normal humans have apoAI concentrations
Q60905 - of approximately 1.6 g/L, the NMR data suggest that each HDL
Q60906 - particle averages <2 copies of apoAI. On the other hand, IM
Q60907 - predicts some 13 apoAI molecules per particle. Both differ
Q60908 - from biochemical measurements of isolated HDL samples
Q60909 - indicating an average of 3-4 apoAI molecules per particle (12,
Q60910 - 13).
Q60912 - ..
Q60913 - The report by Hutchins et al. in this issue of Clinical
Q60914 - Chemistry directly addresses this HDL-P accuracy problem (14).
Q60915 - Building on the IM approach, they used a set of purified
Q60916 - proteins of known size and concentration to internally
Q60917 - calibrate the method. This allowed for an accounting of the
Q60918 - significant variability in the production of gas-phase ions
Q60919 - that underpins the analysis, permitting the conversion of the
Q60920 - relative IM signal intensity to an absolute concentration.
Q60921 - They dubbed this calibrated ion mobility (CIM). Using a signal
Q60922 - deconvolution paradigm that reveals large, medium, and small
Q60923 - HDL particles, they validated the method
Q60925 - ..
Q60926 - using gold nanoparticles and reconstituted HDL particles of
Q60927 - highly defined size, concentration, and stoichiometry. They
Q60928 - observed impressive correlations between the CIM value and
Q60929 - known particle concentrations for both analytes. But most
Q60930 - importantly, the experimental values matched the benchmark
Q60931 - values within 15%, indicating good accuracy as well. The
Q60932 - validated method was used to determine HDL-P in a cohort of 40
Q60933 - controls and 40 individuals with carotid cerebrovascular
Q60934 - disease. Overall, 3 HDL subspecies were identified, with
Q60935 - masses and diameters consistent with biochemical measurements.
Q60936 - Furthermore, the average HDL-P concentration was consistent
Q60937 - with 34 molecules of apoAI per particle. In line with the
Q60938 - reports described above, the CIM-derived HDL-P value was
Q60939 - significantly better than HDL-C for identifying afflicted
Q60940 - individuals, even in the quite small sample size of 80
Q60941 - individuals.
Q60943 - ..
Q60944 - Aside from the direct calibration and accuracy gains, CIM has
Q60945 - an advantage over the NMR technique in that it is a direct
Q60946 - measure of holo-particle size (i.e., using all components)
Q60947 - rather than relying on signal generated by 1 component that can
Q60948 - vary highly among HDL species (lipid). However, this also
Q60949 - contributes to a major drawback of the CIM method, namely the
Q60950 - requirement that HDL must be first isolated from other serum
Q60951 - components before the analysis. NMR can be applied directly to
Q60952 - serum samples. Because antibodies and other large plasma
Q60953 - proteins overlap with many HDL size species, the HDL samples
Q60954 - analyzed by Hutchins et al. were first isolated from serum by
Q60955 - density ultracentrifugation. This is an issue for 3 reasons.
Q60956 - First, the labor-intensive separation pretty much precludes the
Q60957 - use of this assay in most standardized and high-throughput
Q60958 - clinical testing settings. Second, it is well documented that
Q60959 - ultracentrifugation can result in the loss of certain
Q60960 - apolipoproteins, and a redistribution of HDL subspecies cannot
Q60961 - be completely ruled out (15). Third, extrapolation of the CIM
Q60962 - value determined on purified HDL samples back to circulating
Q60963 - plasma HDL-P concentrations requires careful accounting of
Q60964 - volumes, dilutions, and sample loss during the separationall
Q60965 - of which can lead to increased variability. Nevertheless, the
Q60966 - approach has significant potential for accurately analyzing
Q60967 - samples in small clinical studies at a single site.
Q60969 - ..
Q60970 - The major strength of all 3 HDL-P methods is the ability to
Q60971 - track the numbers of HDL particles and monitor changes in their
Q60972 - size subspecies in response to disease. This may point to
Q60973 - specific metabolic processes that underlie the formation of
Q60974 - each subspecies and thereby provide new information on the
Q60975 - pathways that, either directly or indirectly, tie HDL to CVD.
Q60976 - Furthermore, these methods should prove useful to track
Q60977 - reversion to healthier lipoprotein patterns induced by
Q60978 - experimental therapeutics. From a basic science perspective,
Q60979 - CIM should also prove highly useful for monitoring HDL particle
Q60980 - size changes in vitro during perturbations such as lipase or
Q60981 - lipid transfer protein additions, for example. Finally, it is
Q60982 - hoped that the practitioners of all the HDL-P methods discussed
Q60983 - here will collaborate, perhaps by adopting a set of universal
Q60984 - calibration standards or even using CIM as a reference method,
Q60985 - to resolve discrepancies among the methods so that direct
Q60986 - comparisons can eventually be made across studies.
Q60987 -
Q60988 -
Q60989 -
Q60990 -
Q610 -
SUBJECTS
Default Null Subject Account for Blank Record
Q703 -
Q70401 - ..
Q70402 - Exercise Increases HDL and Reverse Cholesterol Transport RCT
Q70403 -
Q70404 -
Q70405 - Article...
Q70406 -
Q70407 - PMC
Q70408 - US National Library of Medicine
Q70409 - National Institutes of Health
Q70411 - ..
Q70412 - Frontiers in Physiology
Q70414 - ..
Q70415 - Published online 2018 May 15 doi: 10.3389/fphys.2018.00526
Q70417 - ..
Q70418 - PMDID: PMC5962737
Q70419 - PMID: 29867567
Q70421 - ..
Q70422 - Reverse Cholesterol Transport: Molecular Mechanisms and the
Q70423 - Non-medical Approach to Enhance HDL Cholesterol
Q70424 -
Q70425 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962737/
Q70427 - ..
Q70428 - Abstract
Q70430 - ..
Q70431 - Dyslipidemia (high concentrations of LDL-c and low
Q70432 - concentrations of HDL-c) is a major cause of cardiovascular
Q70433 - events, which are the leading cause of death in the world. On
Q70434 - the other hand, nutrition and regular exercise can be an
Q70435 - interesting strategy to modulate lipid profile, acting as
Q70436 - prevention or treatment, inhibiting the risk of diseases due to
Q70437 - its anti-inflammatory and anti-atherogenic characteristics.
Q70438 - Additionally, the possibility of controlling different training
Q70439 - variables, such as type, intensity and recovery interval, can
Q70440 - be used to maximize the benefits of exercise in promoting
Q70441 - cardiovascular health. However, the mechanisms by which
Q70442 - exercise and nutrients act in the regulation of cholesterol and
Q70443 - its fractions, such as reverse cholesterol transport, receptors
Q70444 - and transcription factors involved, such as PPARs and their
Q70445 - role related to exercise, deserve further discussion.
Q70446 - Therefore, the objective of this review is to debate about
Q70447 - non-medical approaches to increase HDL-c, such as nutritional
Q70448 - and training strategies, and to discuss the central mechanisms
Q70449 - involved in the modulation of lipid profile during exercise, as
Q70450 - well as that can be controlled by physical trainers or sports
Q70451 - specialists in attempt to maximize the benefits promoted by
Q70452 - exercise. The search for papers was performed in the
Q70453 - databases: Medline (Pubmed), Science Direct, Scopus, Sport
Q70454 - Discus, Web of Science, Scielo and Lilacs until February 2016.
Q70456 - ..
Q70457 - Keywords: exercise, physical training, functional foods,
Q70458 - nutritional strategies, lipoproteins, dyslipidemias
Q70460 - ..
Q70461 - Introduction
Q70463 - ..
Q70464 - Physical inactivity contributes to increased cardiovascular
Q70465 - diseases, such as atherosclerosis, which are leading causes of
Q70466 - death worldwide (Rosamond et al., 2008). The high
Q70467 - concentration of low-density lipoprotein cholesterol (LDL-c) is
Q70468 - an independent risk factor for coronary artery disease. It
Q70469 - competes with plasminogen by binding sites, reducing the
Q70470 - plasmin generation and inhibiting fibrinolysis, therefore, the
Q70471 - thrombus formed due to ruptured atherosclerotic plaque triggers
Q70472 - ischemic cardiovascular events (Schmitz and Orsó, 2015). On
Q70473 - the other hand, there is an inverse relationship between
Q70474 - high-density lipoprotein cholesterol (HDL-c) and incidence of
Q70475 - coronary heart disease. It was shown that 1-mg/dL increment in
Q70476 - HDL-c was associated with a significant decrease (3.7% in men
Q70477 - and 4.7% in women) in cardiovascular disease mortality rates,
Q70478 - according to a classical study conducted by The British
Q70479 - Regional Heart (Gordon et al., 1989). In addition, recently,
Q70480 - Madsen et al. (2017) showed that an extreme high concentration
Q70481 - of HDL cholesterol was associated with all-cause mortality in
Q70482 - both men and women. The authors shown that men with HDL
Q70483 - cholesterol of 2.5?2.99 mmol/L (97?115 mg/dL) increased 1.36
Q70484 - (95% CI: 1.09?1.70) all-cause mortality and HDL cholesterol ?
Q70485 - 3.0 mmol/L (116 mg/dL) were associated with a significant
Q70486 - increase of 2.06 (1.44?2.95). For women, hazard ratios were
Q70487 - 1.10 (0.83?1.46) for HDL cholesterol of 3.0?3.49 mmol/L
Q70488 - (116?134 mg/dL) and 1.68 (1.09?2.58) for HDL cholesterol ?3.5
Q70489 - mmol/L (135 mg/dL).
Q70491 - ..
Q70492 - Several studies have investigated non-pharmacological
Q70493 - strategies of prevention and treatment of dyslipidemia, such as
Q70494 - enhanced HDL-c by increased physical activity, improved diet,
Q70495 - or a combination of these in different populations. A recently
Q70496 - systematic review analyzed the positives and negatives of
Q70497 - behavioral counseling for the primary prevention of
Q70498 - cardiovascular disease in adults without known cardiovascular
Q70499 - risk factors. It was included 88 studies in this review (N =
Q70500 - 121,190) in 145 publications and observed a reduction in the
Q70501 - LDL-c (-2.58 mg/dL [95% CI, -4.30 to -0.85] in 13 trials [n =
Q70502 - 5554]), and total cholesterol concentration (-2.85 mg/dL [95%
Q70503 - CI, -4.95 to -0.75] in 19 trials [n = 9325]). They concluded
Q70504 - that physical activity and behavioral diet programs for adults
Q70505 - without high risk for cardiovascular disease showed benefits on
Q70506 - LDL-c and total cholesterol. Additionally, the authors
Q70507 - analyzed the dose-response effect of the interventions and
Q70508 - found that higher-intensity exercise programs demonstrated
Q70509 - greater improvements (Patnode et al., 2017).
Q70511 - ..
Q70512 - Also, our group investigated the individual characteristics of
Q70513 - body composition and metabolic profile that explain
Q70514 - interindividual variation in HDL-c concentrations in response
Q70515 - to 16 weeks of combined strength and aerobic training in
Q70516 - postmenopausal women. We concluded that the positive
Q70517 - responders had around 11% less HDL-c (6.31 mg/dL) at baseline
Q70518 - than negative responders, suggesting that the positive response
Q70519 - to combined training is also mediated by the metabolic health
Q70520 - of the individual at baseline (Diniz et al., 2017).
Q70522 - ..
Q70523 - Lipid metabolism involves several pathways that are, at least
Q70524 - in part, interdependent, such as hepatic synthesis of very
Q70525 - low-density lipoprotein (VLDL); uptake of fatty acids (FA) by
Q70526 - skeletal muscle and / or adipose tissue; extrahepatic
Q70527 - transport of cholesterol by low density lipoprotein; and
Q70528 - removal of excess cholesterol by high density lipoproteins
Q70529 - (HDL-c). Although exercise has been used as a cardioprotective
Q70530 - intervention, the mechanisms involved still need to be fully
Q70531 - elucidated. Therefore, the purpose of this review is to
Q70532 - discuss the mechanisms involved in the HDL-c response during
Q70533 - exercise, as well as how the manipulating of different
Q70534 - training variables and nutrients could potentiate these
Q70535 - benefits.
Q70536 -
Q70537 - *********************
Q70539 - ..
Q70540 - Reverse Cholesterol Transport (RCT)
Q70542 - ..
Q70543 - Reverse cholesterol transport is a mechanism by which the body
Q70544 - removes excess cholesterol from peripheral tissues and
Q70545 - delivers them to the liver, where it will be redistributed to
Q70546 - other tissues or removed from the body by the gallbladder. The
Q70547 - main lipoprotein involved in this process is the HDL-c. First,
Q70548 - the intestine and liver synthesize the protein Apo A-1 (70% of
Q70549 - the protein content of HDL-c), which enters the bloodstream
Q70550 - and goes to peripheral tissues (e.g., heart). In veins and
Q70551 - arteries, Apo A-1 interacts with receptors in various cell
Q70552 - types (hepatocyte, enterocytes, and macrophages) called
Q70553 - ATP-Binding Cassette, Sub-Family A (ABC1), Member 1 (ABCA1)
Q70554 - (Leaf, 2003; Chapman et al., 2010).
Q70556 - ..
Q70557 - In macrophages, phagocytes of the immune system specialized in
Q70558 - digesting particles, the interaction with this protein makes
Q70559 - the cholesterols and some lipids (phospholipids) move toward
Q70560 - the molecule Apo A-1. This process results in the formation of
Q70561 - nascent HDL-c particles (pre-? HDL), which subsequently can
Q70562 - interact with Scavenger receptor class B member 1 (SR-B1) and
Q70563 - ATP-binding cassette, sub-family G, member 1 (ABCG1), with the
Q70564 - purpose of incorporating more cholesterol, forming a mature
Q70565 - molecule of HDL-c (?-HDL). These processes are catalyzed by
Q70566 - the enzyme Lecithin-cholesterol acyltransferase (LCAT).
Q70568 - ..
Q70569 - Subsequently, there are two ways where cholesterol is delivered
Q70570 - to the liver: direct and indirect. In the first, mature
Q70571 - molecules of HDL-c interact with SR-B1 in the liver, which
Q70572 - allows the transfer of its cholesterol content. The resulting
Q70573 - HDL-c molecule can resume circulation and repeat the RCT
Q70574 - process. Indirectly, mature molecules of HDL-c transfer its
Q70575 - cholesterol content to apolipoproteins B-100 (Apo B-100),
Q70576 - especially to the low-density lipoprotein (LDL), in exchange
Q70577 - for triacylglycerol molecules. This process is catalyzed by the
Q70578 - enzyme cholesteryl ester transfer protein (CETP). Thus, these
Q70579 - lipoproteins can be associated with their liver receptors and
Q70580 - deliver their cholesterol content (Cavelier et al., 2006;
Q70581 - Rader, 2006). It is worth mentioning that CETP also catalyzes
Q70582 - the reverse transference, i.e., triacylglycerol from HDL-c in
Q70583 - exchange for Apo B-100 cholesterol.
Q70585 - ..
Q70586 - HDL cholesterol content in plasma seems to be crucial in both
Q70587 - prevention and treatment of atherosclerotic diseases, since
Q70588 - this molecule exerts anti-inflammatory functions as well as
Q70589 - exerts positive effects on CRT. However, recent studies have
Q70590 - suggested that not only HDL cholesterol amount, but
Q70591 - functionality has a much greater potential in some diseases
Q70592 - such as coronary artery disease (CAD), chronic renal disease
Q70593 - (CKD), dyslipidemia, diabetes and chronic ischemic
Q70594 - cardiomyopathy. HDL may be affected by myeloperoxidase (MPO),
Q70595 - 15-lipoxygenase (15- LPO), symmetrical dimethylarginine (SDMA)
Q70596 - and other possible markers of this dysfunction. These effects
Q70597 - altered HDL, reducing the availability of endothelial nitrate
Q70598 - oxide, leading to problems of endothelial repair, increasing
Q70599 - proinflammatory activation, and leading to efflux of
Q70600 - macrophages, interfering in its functionality. These findings
Q70601 - are only in the beginning and further researches must be
Q70602 - conducted to understand the implications of abnormal HDL in the
Q70603 - pathogenesis of atherosclerotic cardiovascular diseases and its
Q70604 - clinic aplication. (Xu et al., 2013; Rosenson et al., 2016).
Q70606 - ..
Q70607 - Influence of Training Variables on Lipoproteins and RCT
Q70609 - ..
Q70610 - Several benefits of regular exercise are observed in the lipid
Q70611 - profile, being indicated as one of the best non-pharmacological
Q70612 - strategies in the prevention and treatment of immune-metabolic
Q70613 - disorders (Neto et al., 2011). In this perspective, exercise is
Q70614 - indicated as treatment of several metabolic diseases because of
Q70615 - its effective anti-inflammatory and anti-atherogenic effect.
Q70616 - However, training variables, such as physical fitness
Q70617 - condition, training models (aerobic or strength), intensity,
Q70618 - volume, and recovery intervals, can be controlled in an attempt
Q70619 - to obtain great effectiveness of different training models in
Q70620 - the RCT as described in Table ?Table11.
Q70622 - ..
Q70623 - Problem with this table is that no numerical results are posted for
Q70624 - HDL, blood pressure, heart rate....
Q70626 - ..
Q70627 - Table 1
Q70629 - ..
Q70630 - Author Sample Exercise Protocol Results
Q70632 - ..
Q70633 - Gupta et Professional Cycling and running a Free cholesterol flow
Q70634 - al, 1993 Athletes (N= rate of 5.185 +/- 501 LCAT activity
Q70635 - 11 kcal/week CETP activity
Q70636 - ?LDL-c
Q70637 - ?Apo-B
Q70638 -
Q70640 - ..
Q70641 - Vaisberg Professional Marathon race exercising HDL-c
Q70642 - et al. Athletes (N= at the rate of 80?100 ApoA-1
Q70643 - 2012 14 km/week Transfers of non-
Q70644 - esterified cholesterol
Q70645 - triacylglycerol
Q70646 - IL-6
Q70647 - TNF-?
Q70648 -
Q70650 - ..
Q70651 - Olchawa Professional Endurance exercises VO2max
Q70652 - et al, Athletes (N= (triathlon, biathlon, HDL-c
Q70653 - 2004 14 running, and swimming) ApoA-1
Q70654 - tested at the ?off pre-?1-HDL
Q70655 - season? period LCAT activity
Q70656 - Cholesterol efflux
Q70657 - capacity
Q70658 -
Q70659 -
Q70661 - ..
Q70662 - Butcher Sedentary Low-intensity exercise ?Total cholesterol
Q70663 - et al, Adults (N= program exercising by HDL-c
Q70664 - 2008 34 walking 3 times/week oxLDL
Q70665 - (10.000 steps/session) PPAR-gamma expression
Q70666 - during 8 weeks oxLDL scavenger
Q70667 - receptor CD36
Q70668 - LXR-?
Q70669 - ABCA1
Q70670 - ABCG1
Q70671 -
Q70672 -
Q70674 - ..
Q70675 - Healthy men Acute high-intensity aerobic exercise (? 90% VO2max)
Q70676 - (N=6) performed at cycle ergometer
Q70678 - ..
Q70679 - Sedentary men Compared high-intensity training [12 intervals at 1
Q70680 - (N=12) min work (90?100 VV O2max) with 1 min active recovery
Q70681 - (50% VV O2max)], and moderate aerobic endurance
Q70682 - training (70?80% VV O2max) during 8 weeks
Q70684 - ..
Q70685 - Adult Men (N= Intermittent sprint cycle training (sprints of 10-s
Q70686 - 11) duration, repeated 15 times with 50 s of rest between
Q70687 - each sprint) during 7 weeks
Q70689 - ..
Q70690 - Healthy men Compared high-intensity training (ten 4-min intervals
Q70691 - (N=11) at a power output to elicit 85?90% of VO2peak) and
Q70692 - moderate intensity (60% VO2peak) in acute session
Q70694 - ..
Q70695 - Professional Running (average time of 206 min)
Q70696 - Athletes (N=
Q70697 - 53)
Q70699 - ..
Q70700 - Metabolic Moderate intensity exercise training (45 min per day
Q70701 - Syndrome at 60 rpm performed 3 times/week) during 3 month
Q70702 - subjects (N=
Q70703 - 30)
Q70705 - ..
Q70706 - Healthy Adults Compared high-intensity intermittent all-out exercise
Q70707 - (N=12) (60 × 8-s bouts interspersed by 12-s passive recovery)
Q70708 - and fixed high-intensity intermittent exercise (100%
Q70709 - maximal aerobic speed, consisted of 1-min repetitions
Q70710 - at 70 rpm separated by 1-min of passive recovery) in
Q70711 - acute session
Q70713 - ..
Q70714 - Postmenopausal Compared combined training (strength plus aerobic
Q70715 - women (N= exercise) and aerobic training during 16 weeks
Q70716 - 65)
Q70717 -
Q70719 - ..
Q70720 - Healthy Adults Compared the recovery time (30 or 90 s) in acute
Q70721 - (N=12) session of exhaustive strength exercises (four sets of
Q70722 - squats and four sets of horizontal bench press)
Q70723 - performed at 90% of 1RM
Q70724 -
Q70726 - ..
Q70727 - The authors concluded that this [...aerobic...] type of
Q70728 - exercise is effective in reducing total cholesterol (-2%),
Q70729 - LDL-c (-3%), triacylglycerol (-5%) and increasing HDL-c (+ 3%)
Q70730 - in women over 18 years of age.
Q70732 - ..
Q70733 - This is not a big benefit for exercising.
Q70734 -
Q70735 - It is important to emphasize that the mechanisms involved in
Q70736 - exercise-mediated beneficial responses are distinct in animal
Q70737 - and human models; in this context, the latter sample is more
Q70738 - explored and, given the practical applicability, the
Q70739 - reproduction of the models should be tested in various
Q70740 - populations. Therefore, while exercise promotes significant
Q70741 - and favorable metabolic modifications mediated by RCT, the
Q70742 - possibility of controlling acute training variables can be used
Q70743 - by practitioners, coaches and/or trainers to induce superior
Q70744 - benefits on lipid profile. However, studies investigating the
Q70745 - influence of these variables in a chronic way are needed;
Q70746 - moreover, the large variety of training protocols, especially
Q70747 - regarding strength training, make comparisons and conclusions
Q70748 - about the findings challenging.
Q70749 -
Q70751 - ..
Q70752 - Table 2 is about rats and shows no quantification of HDL
Q70753 - relative to physical activity.
Q70754 -
Q70756 - ..
Q70757 - Table 3 is about humans and shows no quantification of HDL
Q70758 - relative to physical activity.
Q70759 -
Q70761 - ..
Q70762 - In summary, physical training, especially aerobic exercise,
Q70763 - increases the expression of AMPK and PGC1-alpha, which combined
Q70764 - can activate PPAR. When activated, it moves to the nucleus and
Q70765 - connects to its promoter region, where it transcribes genes
Q70766 - related to oxidative metabolism and transport of lipoproteins,
Q70767 - such as ABCA1 and Apo A-1. These outcomes may provide RCT, and
Q70768 - consequently, a reduced risk of developing cardiovascular
Q70769 - disease (Figure ?Figure11). Despite the importance of PPAR and
Q70770 - other receptors during RCT, it is essential to mention that
Q70771 - this transcription factor responds to exercise in several ways,
Q70772 - including angiogenesis, inhibition of lipogenesis and
Q70773 - mitochondrial activity, suggesting the need for future studies
Q70774 - about the mechanisms of RCT, exercise and the role of PPAR.
Q70776 - ..
Q70777 - This summary is not supported by much data.
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