Insulin Resistance and Cardiovascular Events With Low HDL Cholesterol
The Veterans Affairs HDL Intervention Trial (VA-HIT)
- Sander J. Robins, MD1,
- Hanna Bloomfield Rubins, MD2,
- Fred H. Faas, MD3,
- Ernst J. Schaefer, MD4,
- Marshall B. Elam, MD5,
- James W. Anderson, MD6,
- Dorothea Collins, SCD7 and
- on behalf of the VA-HIT Study Group
- 1Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
- 2Center for Chronic Disease Outcomes Research, VAMC, Minneapolis, Minnesota
- 3Department of Medicine, VAMC, Little Rock, Arkansas
- 4Lipid Research Laboratory, Tufts University School of Medicine, Boston, Massachusetts
- 5Department of Medicine, VAMC, Memphis, Tennessee
- 6Department of Medicine, VAMC, Lexington, Kentucky
- 7Department of Veterans Affairs Cooperative Studies Program Coordinating Center, West Haven, Connecticut
Abstract
OBJECTIVE—To assess the effect of insulin resistance and the benefit of the fibrate, gemfibrozil, on the incidence of major cardiovascular events in subjects with low HDL cholesterol and a broad range of triglyceride values who participated in the Veterans Affairs High Density Lipoprotein Intervention Trial (VA-HIT).
RESEARCH DESIGN AND METHODS—This intention-to-treat analysis, specified as a secondary objective in VA-HIT, determined using Cox proportional hazards models the 5-year combined incidence of nonfatal myocardial infarction, coronary heart disease (CHD) death, or stroke in relation to the presence or absence of insulin resistance (defined by the highest tertile of the homeostasis model assessment of insulin resistance, HOMA-IR) in conjunction with lower and higher levels of HDL cholesterol and triglycerides. The study population consisted of 2,283 men with known coronary heart disease (CHD), treated with either placebo or gemfibrozil, who could be subdivided into groups with diabetes with or without insulin resistance, with no diabetes but insulin resistance, and with neither diabetes nor insulin resistance.
RESULTS—With insulin resistance there was a significantly higher relative risk (RR) of a cardiovascular event both with diabetes (RR of 1.62 with 95% CI of 1.28–2.06) and without diabetes (RR of 1.43 with 95% CI of 1.03–1.98) than without insulin resistance. Throughout both lower and higher ranges of HDL cholesterol and triglycerides, the rate of new cardiovascular events and the reduction of events with gemfibrozil was greater in subjects with insulin resistance than without, despite the finding that an increase in HDL cholesterol and a decrease in triglycerides with gemfibrozil was less with insulin resistance than without insulin resistance.
CONCLUSIONS—Results show that in VA-HIT the occurrence of a new cardiovascular event and the benefit of fibrate therapy was much less dependent on levels of HDL cholesterol or triglycerides than on the presence or absence of insulin resistance.
- CHD, coronary heart disease
- HOMA-IR, homeostasis model assessment of insulin resistance
- MI, myocardial infarction
- VA-HIT, Veterans Affairs High Density Lipoprotein Intervention Trial
Footnotes
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Address correspondence and reprint requests to Sander Robins, MD, Division of Endocrinology, Nutrition, and Diabetes, Boston University School of Medicine, Evans 204, 88 East Newton St., Boston, MA 02118. E-mail: sjrobins{at}bu.edu.
Received for publication 21 November 2002 and accepted in revised form 1 February 2003.
The VA-HIT Study Group is listed in N Engl J Med 341:410–418, 1999. The views expressed in this article do not necessarily represent the views of the Department of Veterans Affairs.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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