Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial

Bela F. Asztalos, Dorothea Collins, Katalin V. Horvath, Hanna E. Bloomfield, Sander J. Robins, Ernst J. Schaefer

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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 preβ-1 and had significantly lower α-1 and α-2 HDL levels than those without such events. Preβ-1 level was a significant positive predictor; α-1 and α-2 levels were significant negative risk factors for future CVD events. α-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 preβ-1 HDL and in the large, lipid-rich α-1 and α-2 HDL and with increases in the small α-3 (3%) and preα-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.

Original languageEnglish (US)
Pages (from-to)77-83
Number of pages7
JournalMetabolism: clinical and experimental
Volume57
Issue number1
DOIs
StatePublished - Jan 2008

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (HL-64738 PI: Asztalos) and by the VA Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, Washington, DC.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

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