Targeting low high-density lipoprotein cholesterol for therapy: lessons from the Veterans Affairs High-density Lipoprotein Intervention Trial

Results of the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) showed that therapy with the fibric acid gemfibrozil significantly reduced the incidence of coronary artery disease events in men with known coronary artery disease and a low level of high-density lipoprotein cholesterol (HDL-C). Coronary artery disease event reduction was inversely related to levels of HDL-C achieved with gemfibrozil and, even at relatively low concentrations of HDL-C, coronary artery disease event reduction with gemfibrozil was significantly greater than with placebo. Subjects with a low HDL-C level who were recruited for VA-HIT had a high prevalence of features of the metabolic syndrome with obesity, type 2 diabetes, and hyperinsulinemia. These individuals especially benefited from gemfibrozil, and thus, fibrate therapy may have an increasing role in reducing coronary artery disease risk in a setting of an increasing worldwide prevalence of obesity and diabetes.