(Circulation. 2000;101:1907.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Elevated HDL Cholesterol Is a Risk Factor for Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein Gene
From the Department of Clinical Biochemistry (B.A.-L., A.T.-H.), Herlev University Hospital, University of Copenhagen, Herlev, Denmark; Department of Clinical Biochemistry (B.G.N.), Glostrup University Hospital, University of Copenhagen, Glostrup, Denmark; The Copenhagen City Heart Study (B.G.N., G.J., A.T.-H.), Bispebjerg University Hospital, University of Copenhagen, Copenhagen NV, Denmark; and Department of Medicine B (R.S.), Division of Cardiology, Rigshospitalet, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
Correspondence to Anne Tybjærg-Hansen, MD, DMSc, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail at-h{at}rh.dk
Background—The level of HDL cholesterol is inversely related to the risk of ischemic heart disease.
Methods and Results—In 9168 women and men from a general population and 946 women and men with ischemic heart disease (all white), we tested the hypothesis that the Ile405Val mutation in the cholesteryl ester transfer protein gene (CETP) affects HDL cholesterol levels and the risk of ischemic heart disease. The relative frequencies of Ile/Ile, Ile/Val, and Val/Val carriers were 0.46, 0.43, and 0.11 for both women and men. Women with these 3 genotypes had mean HDL cholesterol levels of 1.68, 1.75, and 1.82 mmol/L, respectively (P<0.001, ANOVA), as well as a significant decrease in the ratio of total to HDL cholesterol (P=0.002, ANOVA). On multiple logistic regression analysis, women not treated with hormone replacement therapy who were heterozygous or homozygous for Val405 had a 1.4-fold (95% CI 1.0 to 1.9) to 2.1-fold (95% CI 1.3 to 3.4) increase in the risk of ischemic heart disease. No significant associations were found in men.
Conclusions—Increased HDL cholesterol levels caused by mutations in CETP are associated with an increased risk of ischemic heart disease in white women.
Key Words: transfer proteins • genetics • lipoproteins • heart diseases • apolipoproteins
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