Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial.
Open accessAbstract
The significant cardiovascular disease (CVD) event reduction in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) could not be fully explained by the 6% increase in high-density lipoprotein (HDL) cholesterol with the fibrate gemfibrozil. We examined whether measurement of HDL subpopulations provided additional information relative to CVD risk reduction. The HDL subpopulations were characterized by 2-dimensional gel electrophoresis in subjects who were treated with gemfibrozil (n = 754) or placebo (n = 741). In this study, samples obtained at the 3-month visit were used; and data were analyzed prospectively using CVD events (coronary heart disease death, myocardial infarction, or stroke) during the 5.1 years of follow-up. Analyses in the gemfibrozil arm showed that subjects with recurrent CVD events had significantly higher prebeta-1 and had significantly lower alpha-1 and alpha-2 HDL levels than those without such events. Prebeta-1 level was a significant positive predictor; alpha-1 and alpha-2 levels were significant negative risk factors for future CVD events. alpha-2 level was superior to HDL cholesterol level in CVD-risk assessment after adjustment for established risk factors. Gemfibrozil treatment was associated with 3% to 6% decreases in the small, lipid-poor prebeta-1 HDL and in the large, lipid-rich alpha-1 and alpha-2 HDL and with increases in the small alpha-3 (3%) and prealpha-3 (16%) HDLs. Although the use of gemfibrozil has been associated with reduction in CVD events in VA-HIT, HDL subpopulation analysis indicates that gemfibrozil-mediated improvement in CVD risk might not be the result of its effects on HDL. It is quite possible that much of the cardiovascular benefits of gemfibrozil are due to a much wider spectrum of effects on metabolic processes that is not reflected by changes in blood lipids and HDL subpopulations.
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Epidemiological studies have not provided conclusive evidence that measurement of HDL size contributes to risk prediction.
“Epidemiological studies have not provided conclusive evidence that measurement of HDL size contributes to risk prediction (36, 50 -55).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [54]
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BackgroundResultInfluentialQuality Control of HDL: Nutrition and Not Numbers May Determine HDL Functionality
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“The cardiovascular benefits of gemfibrozil were 74 supposed to be due to the effects on metabolic processes not reflected by its 75 modification of lipid profiles (Asztalos et al. 2008).”
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- Authors
- Asztalos, B. F., Collins, D., Horvath, K. V., Bloomfield, H. E., Robins, S. J., & Schaefer, E. J.
- Affiliations
- Tufts University (US)
- West Haven Cooperative Studies Program Coordinating Center (US)
- Minneapolis VA Medical Center (US)
- Boston University (US)
- Corresponding author
- Asztalos, Bela F.
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 57
- Issue
- 1
- Pages
- 77-83
- ISSN
- 0026-0495 (ISSN-L)
- PMC
- PMC2194640
- OpenAlex
- W2146890604
- Cited by
- 71
- References
- 29
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 1 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 4 · 2014: 9 · 2013: 4 · 2012: 4
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Office of Research and Development
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 64738, R01HL064738)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- gemfibrozil, HDL subpopulations, cardiovascular events, fibrate therapy, HDL cholesterol, cardiovascular risk prediction, coronary artery disease, myocardial infarction, stroke
- MeSH terms
- Hypolipidemic Agents, Cardiovascular Diseases, Coronary Disease, Humans, Hypertension, Lipids, Lipoproteins, HDL, Male, Placebos, Prospective Studies, United States, United States Department of Veterans Affairs, Gemfibrozil, Proportional Hazards Models, Risk Reduction Behavior
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