Genetics
Nearly 50,000-subject Japanese study finds no excess coronary heart disease in CETP-deficient people with very high HDL cholesterol (Prev Med 1998)
Original title: 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
Since recent studies had suggested CETP deficiency is a coronary heart disease (CHD) risk factor despite raising HDL-cholesterol, this study cross-sectionally analyzed plasma lipids, CHD prevalence, resting ECGs, and common CETP gene mutations in 19,044 Japanese men and 29,487 Japanese women aged 45-79. High HDL-cholesterol (80 mg/dL or higher, 95th percentile or above) was found in 6% of men and 5% of women. Within this high-HDL group, common CETP mutations were identified in 23-24% of men and 31-49% of women. CHD prevalence in the high-HDL group was low in both men (1.0%) and women (1.3%), with no difference in CHD prevalence between hyper-HDL-cholesterolemic subjects with and without CETP mutations. The authors conclude subjects with very high or mildly-to-moderately elevated HDL-cholesterol appear protected against CHD regardless of CETP deficiency status.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.