Raising high density lipoprotein cholesterol.

The predictive pawer of plasma density lipaprotein (HDL*) cholesterol concentration for the development of coronary heart disease (CHD) has now been demonstrated in four large studies in the U.S.A. (Framingham Heart Study, Lipid Research Clinics-Coronary Primary Prevention Trial [LRCCPPT], LRC Follow-up Study and Multiple Risk Factor Intervention Trial), and similar results have been reported from prospective studies in Norway, Israel, West Germany, Britain and Finland [l]. The collective evidence indicates that the inverse relation of CHD risk to HDL cholesterol is continuous; is independent of the concentrations of very low density (VLDL) and low density (LDL) lipoproteins; is independent of mm-lipid risk factors for CHD, such as cigarette smoking, blood pressure, glucose intolerance and obesity; applies to CHD mortality as well as morbidity; is present in bath middle-aged and elderly subjects; applies to both sexes; and applies to subjects with, as well as those without, a previous history of myocardial ischemia ]I]. In most cohorts the association of CHD with HDL cholesterol has been at Ieast as strong as that with LDL cholesterol. In North American men and women, CHD risk increases on average by 2-3LTo for each 1 mg/dL decrease in HDL cholesterol (and by 1% for each 1 mg/dL increase in LDL cholesterol) [2]. Angiographic studies and exanl~nation of vessels at autopsy have shown that these associations with clinical CHD reflect an underlying association with coronary atherosclerosis f3]. Genetic and pharmacologic studies have implicated a causal effect of HDL metabolism on atherogenesis. In mice variations at gene loci affecting HDL concentration have been found to have major effects on diet-induced atherosclerosis ]4]. In cholesterol-fed rabbits atherogenesis was strongly inhibited by BRL26314, a drug which raises HDL