Published online before print August 30, 2004, doi: 10.1161/01.CIR.0000141730.65972.95
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(Circulation. 2004;110:1418-1423.)
© 2004 American Heart Association, Inc.
Original Articles |
Plasma Levels of Cholesteryl Ester Transfer Protein and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women
The Prospective EPIC (European Prospective Investigation into Cancer and nutrition)–Norfolk Population Study
From the Departments of Cardiology (S.M.B., R.J.G.P.) and Vascular Medicine (J.-A.K., J.J.P.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Cardiology (J.W.J.), Leiden University Medical Center, Leiden, the Netherlands; Medical Research Council Epidemiology Unit, Cambridge, United Kingdom (N.J.W.); Medical Research Council Dunn Nutrition Unit, Cambridge, United Kingdom (S.A.B.); and Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom (R.L., N.E.D., K.-T.K.).
Correspondence to Kay-Tee Khaw, MBBChir FRCP, Clinical Gerontology Unit, Box 251, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge CB2 2QQ, United Kingdom. E-mail kk101{at}medschl.cam.ac.uk
Received May 7, 2004; revision received July 5, 2004; accepted July 14, 2004.
Background— Low plasma levels of cholesteryl ester transfer protein (CETP) are associated with elevated levels of HDL cholesterol (HDL-C), but it remains unclear whether this translates into a concomitant reduction in the risk of coronary artery disease (CAD). Evidence exists that the effect of CETP depends on metabolic context, in particular on triglyceride levels.
Methods and Results— A nested case-control study was performed in the prospective EPIC-Norfolk cohort study. Cases were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during follow-up. Control subjects were matched by age, sex, and enrollment time. CETP levels were not significantly different between cases and controls (4.0±2.2 versus 3.8±2.1 mg/L, P=0.07). CETP levels were significantly related to plasma levels of total cholesterol, LDL cholesterol, and HDL-C. The risk of CAD increased with increasing CETP quintiles (P for linearity=0.02), such that subjects in the highest quintile had an adjusted OR of 1.43 (95% CI 1.03 to 1.99, P=0.03) versus those in the lowest. Among individuals with triglyceride levels below the median (1.7 mmol/L), no relationship between CETP levels and CAD risk was observed (P for linearity=0.5), but this relationship was strong among those with high triglyceride levels (P for linearity=0.02), such that those in the highest CETP quintile had an OR of 1.87 (95% CI 1.06 to 3.30, P=0.02).
Conclusions— Elevated CETP levels are associated with an increasing risk of future CAD in apparently healthy individuals, but only in those with high triglyceride levels.
Key Words: cholesterol • lipoproteins • coronary disease • atherosclerosis
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