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 >/=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.
Moriyama
Y
Y
Kochi Prefectural Institute of Public Health, Marunouchi 2-4-1, Kochi, 780-0850, Japan.
Okamura
T
T
Inazu
A
A
Doi
M
M
Iso
H
H
Mouri
Y
Y
Ishikawa
Y
Y
Suzuki
H
H
Iida
M
M
Koizumi
J
J
Mabuchi
H
H
Komachi
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000097:blood*; D015217:Cholesterol Ester Storage Disease / Q000097:blood / Q000150:complications* / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006937:Hypercholesterolemia; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins