HDL biology
Plasma CETP concentration, not TaqIB genotype, predicts atherosclerosis progression and pravastatin benefit in REGRESS (Eur J Clin Invest 2004)
Original title: Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS)
In 674 men with angiographically proven coronary artery disease from the REGRESS trial, plasma CETP concentration was measured at baseline and after two years of pravastatin or placebo. Subjects in the highest CETP tertile (>2.21 mg/L) had significantly higher baseline total cholesterol, LDL-cholesterol, and triglycerides, and after two years of placebo their coronary segment diameter narrowed three-fold and obstruction diameter narrowed 2.4-fold more than the lowest tertile. Pravastatin reduced lipids most in the highest CETP tertile, and only in that tertile did pravastatin significantly slow segment- and obstruction-diameter narrowing versus placebo, independent of baseline lipids and lipid changes. Strikingly, all these associations held independent of TaqIB genotype, indicating that plasma CETP concentration itself, not the TaqIB variant, is a key determinant of atherosclerosis progression and statin response.
Original abstract
Background: The TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene is associated with HDL-C, progression of coronary artery disease (CAD) and response to pravastatin treatment in men with angiographically proven CAD (REGRESS). We hypothesized that differences in CETP concentration could explain these associations and now investigated whether CETP concentration is an independent determinant of these parameters.
Materials And Methods: Plasma CETP concentrations at baseline and after 2 years' treatment with pravastatin or placebo were measured (n=674), and correlations with lipid and angiographic parameters (mean segment- and obstruction-diameter; MSD and MOD), and TaqIB genotype were studied.
Results: After segregation into three groups (baseline CETP<1.58, 1.58-2.21, >2.21 mg L(-1)), subjects with the highest CETP had significantly higher baseline total cholesterol, LDL-C and triglycerides (P<0.01), while HDL-C, MSD and MOD were not different among these groups. After 2 years of placebo, the MSD decreased threefold (P<0.001) and the MOD decreased 2.4-fold (P=0.042) more in the highest compared with the lowest CETP quartile. Pravastatin treatment reduced total cholesterol LDL-C and triglycerides significantly more in the highest CETP quartile. Moreover, only in the highest CETP quartile, pravastatin significantly reduced the MSD- (P=0.003) and MOD-decrease (P=0.014) compared with placebo, and, notably, this was independent of baseline lipids and differential lipid changes in these quartiles. Strikingly, baseline associations and treatment responses according to baseline CETP were independent of TaqIB genotype.
Conclusions: High CETP concentration is associated with faster progression of coronary atherosclerosis in men with proven CAD. Second, pravastatin yielded the highest improvement of lipid and angiographic parameters in patients with high baseline CETP independent of baseline lipids, lipid changes and TaqIB genotype, indicating that the plasma CETP level itself is an important determinant of the response to statins.
HDL biologyplaque imagingstatins
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.