Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).
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).


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.
Robins
Sander J
SJ
Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA. sjrobins@bu.edu
Rubins
Hanna Bloomfield
HB
Faas
Fred H
FH
Schaefer
Ernst J
EJ
Elam
Marshall B
MB
Anderson
James W
JW
Collins
Dorothea
D
D001824:Body Constitution; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000401:mortality; D015248:Gemfibrozil / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D016016:Proportional Hazards Models; D012016:Reference Values; D012307:Risk Factors; D016019:Survival Analysis; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D015248:Gemfibrozil