PATHOPHYSIOLOGY AND NATURAL HISTORY CORONARY ARTERY DISEASE High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: The Lipid Research Clinics Coronary Primary Prevention Trial

Plasma levels of high-density lipoprotein cholesterol (HDL-C) at entry and subsequent changes from these baseline levels were inversely predictive of coronary heart disease (CHD) end points in hypercholesterolemic men followed for 7 to 10 years in the Lipid Research Clinics Coronary Primary Prevention Trial, especially in the 1907 participants receiving cholestyramine. When the men in this cohort were compared, each 1 mg/dl increment in baseline HDL-C (mean 44.3 mg/dl) was associated with a 5.5% decrement in risk of "definite" CHD death or myocardial infarction (Z = 5.4), and each 1 mg/dl increase from baseline HDL-C levels (mean increase = 1.6 mg/dl) during the trial was associated with a 4.4% risk reduction (Z = -2.2). In the 1899 participants receiving placebo, the corresponding risk decrements were 3.4% and 1.1%. Although baseline HDL-C level (mean = 44.4 mg/dl) remained a significant risk predictor (Z = -3.8) in the placebo cohort, increases in HDLC (mean increase 0.5 mg/dl) were not significantly predictive of CHD (Z = -0.6) unless "suspect" as well as "definite" end points were analyzed (Z = 2.0). When the associations between HDL-C (baseline plus change) and incidence of definite CHD end points within each treatment cohort were compared, their difference approached nominal significance (Z = 1. 9). The results suggest a synergistic interaction, in which cholestyramine treatment reduced CHD risk most substantially in men maintaining the highest HDL-C levels. Circulation 74, No. 6, 121 7-1225, 1986 AN INVERSE ASSOCIATION of high density lipoprotein cholesterol (HDL-C) levels and rates of coronary heart disease (CHD) incidence and mortality has been observed in prospective epidemiologic studies conducted in several countries.'" In six of these studies,I4A 8 9 this inverse association was statistically significant and remained so after adjustment for other risk factors. Although the underlying mechanism for this From the Lipid Metabolism-Atherogenesis Branch and the Division of Epidemiology and Clinical Applications, National Institutes of Health, Bethesda, MD; the Lipid Research Clinics Program, Department of Biostatistics, and Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill; and the Stanford Heart Disease Prevention Program, Stanford University School of Medicine, Palo Alto, CA. Supported by NHLBI contracts NOl-HV12156, NOl-HV22914, YO1-HV30010, NOI-HV22913, NOl-HV12158, NO-HV12161, NOlHV22915, NO-HV22917, NO-HV12243, NO-HV32961, and NOHV62941. Address for correspondence: David J. Gordon, M.D., Ph.D., Lipid Metabolism-Atherogenesis Branch, NHLBI, National Institutes of Health, Room 401, Federal Bldg., Bethesda, MD 20892. Received June 16, 1986; revision accepted Aug. 28, 1986. Vol. 74, No. 6, December 1986 inverse association is not fully understood, it is hypothesized that HDL promotes the removal of free cholesterol from peripheral tissues and its transport to the liver for eventual clearance.'0 The present report addresses the degree to which HDL-C levels predicted fatal and nonfatal CHD outcomes in initially asymptomatic 35to 59-year-old hypercholesterolemic men who participated in the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). "1-14 This multicenter, double-blind, randomized clinical trial tested the hypothesis that lowering plasma low-density lipoprotein cholesterol (LDLC) levels would reduce the combined incidence of definite CHD death and nonfatal myocardial infarction. The incidence of CHD manifestations was significantly lower among the 1907 men assigned to receive diet plus cholestyramine resin than among the 1899 men assigned to receive the identical diet plus a placebo.'2 Within each of these two treatment cohorts, CHD incidence was found to be lowest among men 1217 by gest on A ril 9, 2017 http://ciajournals.org/ D ow nladed from