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 of risk factors for disease. A high plasma level of high-density lipoprotein (HDL) cholesterol is a strong negative risk factor for coronary heart disease (CHD). Cholesteryl ester transfer protein (CETP) deficiency causes increased levels of HDL cholesterol, However, recent studies suggest that CETP deficiency is a risk factor for CHD despite elevated HDL cholesterol levels, Methods. Plasma lipid levels, CHD prevalence, resting electrocardiograms, and common CETP gene mutations were analyzed cross-sectionally in a population of 19,044 male and 29,487 female Japanese subjects (ages 45-79 years). Results. High HDL cholesterol levels (serum HDL cholesterol greater than or equal to 80 mg/dl, greater than or equal to 95th percentile) were found in 6 and 5% of Japanese men and women, respectively. In the group with HDL cholesterol greater than or equal to 80 mg/dl, common CETP gene mutations were identified 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) was 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 levels (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 against CHD, whether or not they have CETP deficiency, a genetic cause of elevated HDL. (C) 1998 American Health Foundation and Academic Press.