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.