Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial.
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.
Asztalos
Bela F
BF
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. bela.asztalos@tufts.edu
Collins
Dorothea
D
Horvath
Katalin V
KV
Bloomfield
Hanna E
HE
Robins
Sander J
SJ
Schaefer
Ernst J
EJ
D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003327:Coronary Disease / Q000453:epidemiology* / Q000517:prevention & control; D015248:Gemfibrozil / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood* / Q000145:classification; D008297:Male; D010919:Placebos; D016016:Proportional Hazards Models; D011446:Prospective Studies; D040242:Risk Reduction Behavior; D014481:United States; D014493:United States Department of Veterans Affairs
D000960:Hypolipidemic Agents; D008055:Lipids; D008075:Lipoproteins, HDL; D010919:Placebos; D015248:Gemfibrozil