Landmark REGRESS trial finds the CETP B1B1 genotype predicts who benefits from pravastatin against coronary atherosclerosis progression (N Engl J Med 1998)

Original title: The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group

N Engl J Med · 8 January 1998 · 9

Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ

This REGRESS trial substudy analyzed the DNA of 807 men with angiographically documented coronary atherosclerosis for a CETP gene polymorphism (B1 presence versus B2), among patients randomized to pravastatin or placebo for two years in a cholesterol-lowering trial designed to induce regression of coronary atherosclerosis. The B1 variant was associated with both higher plasma CETP concentration (2.29 vs 1.76 microgram/mL for B1B1 vs B2B2) and lower HDL-cholesterol (34 vs 39 mg/dL). In the placebo group, a significant dose-dependent association was found between this marker and atherosclerosis progression (mean luminal diameter decrease: 0.14 mm for B1B1, 0.10 mm for B1B2, 0.05 mm for B2B2), an association abolished by pravastatin, which slowed progression in B1B1 carriers but not B2B2 carriers (16% of pravastatin-treated patients). The authors conclude this CETP variant predicts progression of coronary atherosclerosis independent of HDL-cholesterol, and predicts pravastatin benefit.

Original abstract

Background: The high-density lipoprotein (HDL) cholesterol concentration is inversely related to the risk of coronary artery disease. The cholesteryl ester transfer protein (CETP) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis.

Methods: The DNA of 807 men with angiographically documented coronary atherosclerosis was analyzed for the presence of a polymorphism in the gene coding for CETP. The presence of this DNA variation was referred to as B1, and its absence as B2. All patients participated in a cholesterol-lowering trial designed to induce the regression of coronary atherosclerosis and were randomly assigned to treatment with either pravastatin or placebo for two years.

Results: The B1 variant of the CETP gene was associated with both higher plasma CETP concentrations (mean [+/-SD], 2.29+/-0.62 microg per milliliter for the B1B1 genotype vs. 1.76+/-0.51 microg per milliliter for the B2B2 genotype) and lower HDL cholesterol concentrations (34+/-8 vs. 39+/-10 mg per deciliter). In addition, we observed a significant dose-dependent association between this marker and the progression of coronary atherosclerosis in the placebo group (decrease in mean luminal diameter: 0.14+/-0.21 mm for the B1B1 genotype, 0.10+/-0.20 mm for the B1B2 genotype, and 0.05+/-0.22 mm for the B2B2 genotype). This association was abolished by pravastatin. Pravastatin therapy slowed the progression of coronary atherosclerosis in B1B1 carriers but not in B2B2 carriers (representing 16 percent of the patients taking pravastatin).

Conclusions: There is a significant relation between variation at the CETP gene locus and the progression of coronary atherosclerosis that is independent of plasma HDL cholesterol levels and the activities of lipolytic plasma enzymes. This common DNA variant appears to predict whether men with coronary artery disease will benefit from treatment with pravastatin to delay the progression of coronary atherosclerosis.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.