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☆☆☆

Abstract 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 ≥80 mg/dl, ≥95th percentile) were found in 6 and 5% of Japanese men and women, respectively. In the group with HDL cholesterol ≥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 (≥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 ≥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.