A LOW-PREVALENCE OF CORONARY HEART-DISEASE AMONG SUBJECTS WITH INCREASED HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL LEVELS, INCLUDING THOSE WITH PLASMA CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY

Background. Use of genetic analysis may improve the predictive value o f risk factors for disease. A high plasma level of high-density lipopr otein (HDL) cholesterol is a strong negative risk factor for coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) deficie ncy causes increased levels of HDL cholesterol, However, recent studie s suggest that CETP deficiency is a risk factor for CHD despite elevat ed HDL cholesterol levels, Methods. Plasma lipid levels, CHD prevalenc e, resting electrocardiograms, and common CETP gene mutations were ana lyzed cross-sectionally in a population of 19,044 male and 29,487 fema le Japanese subjects (ages 45-79 years). Results. High HDL cholesterol levels (serum HDL cholesterol greater than or equal to 80 mg/dl, grea ter than or equal to 95th percentile) were found in 6 and 5% of Japane se men and women, respectively. In the group with HDL cholesterol grea ter than or equal to 80 mg/dl, common CETP gene mutations were identif ied in 23-24% of men and 31-49% of women. The prevalence of CHD in the group with high HDL cholesterol (greater than or equal to 80 mg/dl) w as low among both men (1.0%) and women (1.3%). There was no difference in CHD prevalence between hyper-HDL-cholesterolemic subjects with and without CETP mutations. Conclusions. Subjects with very high HDL leve ls (HDL cholesterol greater than or equal to 80 mg/dl) as well as mild -to-moderate HDL elevations (60-79 mg/dl) appear to be protected again st CHD, whether or not they have CETP deficiency, a genetic cause of e levated HDL. (C) 1998 American Health Foundation and Academic Press.