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High HDL not Prophylactic

 

Standard wisdom of high HDL being good unsupported by large Danish study.  This is consistent with the analysis contained in this site.  Namely that it isn’t the LDL and VDL level that is fundamental, but rather oxidative damage to LDL and VDL, and the white blood cells’ response to such damage.  Of course having high levels of LDL and VDL entails a higher rate of damage LDL and VDL contributing to plaque formation.  But there is no known mechanism by which HDL would affect this process, nor has it been worked out how the putative high HDL was prophylactic. 

 

 

JAMA, Vol. 299, No. 21, June 4, 2008

 

Association of Loss-of-Function Mutations in the ABCA1 Gene With High-Density Lipoprotein Cholesterol Levels and Risk of Ischemic Heart Disease

Ruth Frikke-Schmidt, MD, PhD; Børge G. Nordestgaard, MD, DMSc; Maria C. A. Stene, MSc, PhD; Amar A. Sethi, MD, PhD; Alan T. Remaley, MD, PhD; Peter Schnohr, MD; Peer Grande, MD, DMSc; Anne Tybjærg-Hansen, MD, DMSc

JAMA. 2008;299(21):2524-2532.

Context  Low levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Whether this is a causal effect is unclear.

Objective  To determine whether genetically reduced HDL cholesterol due to heterozygosity for 4 loss-of-function mutations in ABCA1 cause increased risk of ischemic heart disease (IHD).

Design, Setting, and Participants  Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study (CCHS), a 31-year prospective general population study (n = 9022; 28 heterozygotes); the Copenhagen General Population Study (CGPS), a cross-sectional general population study (n = 31 241; 76 heterozygotes); and the Copenhagen Ischemic Heart Disease Study (CIHDS), a case-control study (n = 16 623; 44 heterozygotes). End points in all 3 studies were recorded during the period of January 1, 1976, through July 9, 2007.

Main Outcome Measures  Levels of HDL cholesterol in the general population, cellular cholesterol efflux, and the association between IHD and HDL cholesterol and genotype.

Results  Heterozygotes vs noncarriers for 4 ABCA1 mutations (P1065S, G1216V, N1800H, R2144X) had HDL cholesterol levels of 41 mg/dL (interquartile range, 31-50 mg/dL) vs 58 mg/dL (interquartile range, 46-73 mg/dL), corresponding to a reduction in HDL cholesterol of 17 mg/dL (P < .001). A 17-mg/dL lower HDL cholesterol level in the CCHS was associated with a multifactorially adjusted hazard ratio for IHD of 1.70 (95% confidence interval [CI], 1.57-1.85). However, for IHD in heterozygotes vs noncarriers, the multifactorially adjusted hazard ratio was 0.67 (95% CI, 0.28-1.61; 1741 IHD events) in the CCHS, the multifactorially adjusted odds ratio was 0.82 (95% CI, 0.34-1.96; 2427 IHD events) in the CGPS, and the multifactorially adjusted odds ratio was 0.86 (95% CI, 0.32-2.32; 2498 IHD cases) in the CIHDS. The corresponding odds ratio for IHD in heterozygotes vs noncarriers for the combined studies (n = 41 961; 6666 cases; 109 heterozygotes) was 0.93 (95% CI, 0.53-1.62).

Conclusion  Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD.


Author Affiliations: Department of Clinical Biochemistry, Rigshospitalet (Drs Frikke-Schmidt, Stene, and Tybjærg-Hansen), Department of Cardiology, Rigshospitalet (Dr Grande), Department of Clinical Biochemistry, Herlev Hospital (Dr Nordestgaard), Copenhagen City Heart Study, Bispebjerg Hospital (Drs Nordestgaard, Schnohr, and Tybjærg-Hansen), Copenhagen General Population Study, Herlev Hospital (Drs Frikke-Schmidt, Nordestgaard, and Tybjærg-Hansen), Copenhagen University Hospitals, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and Lipoprotein Metabolism Section, Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (Drs Sethi and Remaley).


 

FiercePharma at http://www.fiercepharma.com/story/does-hdl-help-prevent-heart-disease/2008-06-04?utm_medium=nl&utm_source=internal&cmp-id=EMC-NL-FP&dest=FP#comment

 

2. Does HDL help prevent heart disease?

 

Comment | Forward

Scientists have linked high-density lipoproteins (HDL), also known as "good" cholesterol, to lower cardiovascular risk for quite some time, but the Journal of the American Medical Association released a study on June 3, 2008, saying that HDL might not be protective after all.

The study looked at 57,000 Danish patients between 1976 and 2007 and found no protective effect on heart disease. Included in the patient population were 148 individuals with Tangier disease, a rare genetic condition. Of relevance, individuals with Tangier disease have very low HDL levels, so researchers expected that their chance of having heart disease would be double those without the disease, but the study found that they were not at increased risk, even after adjusting for age and heart disease risk factors. 

To date, drug makers have spent over $1 billion based on the belief that HDL helps unclog arteries. Previous studies included individuals with both high triglycerides and low HDL, but the triglycerides might have caused the increased risk. Thus far, the majority of data on HDL relies on animal studies and it is not clear that results will translate to humans, according to lead study author Tybjaerg-Hansen. 

Pfizer spent big bucks on its now-infamous drug torcetrapib, which it did show to raise HDL levels, but did not prove cardiovascular benefits. In fact, it increased deaths, leading to Pfizer discontinuing research in early 2007. Other major developers of drugs to increase HDL include Merck and Roche. While Pfizer's torcetrapib program has been halted, Merck will not be stopping research, since the company believes there remains significant evidence that increasing HDL provides cardiovascular benefits. Roche plans to take its drug to FDA for approval sometime after 2011. 

 

Enter supporting content here

Those who have a financial interest in the outcome manipulate the results, Major study finds that all 37 journal articles positive effects over stated; the average was 32%. Statins cause erectile dysfunction, cognitive imparement, and cancer.  

Lipitor (2011) lifetime sales $131 billion, tops all drugs.  Plavix at $60 billion is second.

 

STATINS CANCER Link

52% short term

 

LA Times, Health section, July 21, 2008  --  excerpts

Vytorin, the combination drug (simvastatin (better known by its commercial name Zocor) and ezetimibe--known as Zetia) prescribed to lower cholesterol, sustained another blow today, when the author of a major clinical trial announced that the medication had failed to drive down hospitalization and death due to heart failure in patients with narrowing of the aortic valve. In the process, researchers in Norway detected a significant blip in cancers in the 1,800 subjects they followed

Today's findings suggested something more ominous: the incidence of cancer -- and of dying of cancer -- was significantly higher in the patients taking Vytorin. Altogether, 67 patients on placebo developed cancer during the trial. Among subjects on Vytorin, 102 developed cancers of various kinds.*  This is the second adverse press—the first being in March 08, when the ENHANCE trial found that Vytorin fared no better than a placebo at reducing plaque buildup on the walls of patients' arteries.* *

Comments by jk

Simvastatin (Zocor) is off patent.  Thus in a scramble for profits a combination drug (on patent) was introduced.  Direct to consumer market cost $155 in 07—mainly TV ads. 

*  The pressing issue is that since the development  of Statins, the very first animal studies in the 60s it has been known that Statins increase the incidents of cancer.  However, nearly all studies done thereafter have not included cancer. 

*  Several studies have failed to find a reduction in the build of plaque, even thought the statins including Zocor, reduce LDL and cholesterol.  Few studies include the principle reason for taking a statin, namely a reduction in the death rate.  Claims for such reduction probably entail a failure to control the contravening variable, aspirin usage.  Given a pile of evidence, including the very mechanism of plaque formation, which involves inflammation process, I must conclude that the use of statins is highly suspect.  Given the harm done including cognitive impairment, weakness, and cancer, if my skepticism is born out, the harm done by statins as a course of treatment will far surpass that of VIOXX which killed over 200,000 people world wide by accelerating atherosclerosis. 

 EXTENDED RELEASE NIACIN IS A SAFER, AND A MORE EFFECTIVE WAY TO LOWER MI RISK!