Cholesteryl ester transfer protein concentration is associated with progression of atherosclerosis and response to pravastatin in men with coronary artery disease (REGRESS)

• Published in: European journal of clinical investigation Vol. 34; no. 1; pp. 21 - 28
• Main Authors: Klerkx, A. H. E. M., De Grooth, G. J., Zwinderman, A. H., Jukema, J. W., Kuivenhoven, J. A., Kastelein, J. J. P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2004; Blackwell
• Subjects: Angiography; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carrier Proteins - blood; Carrier Proteins - genetics; CETP; Cholesterol - blood; Cholesterol Ester Transfer Proteins; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Coronary Angiography; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - drug therapy; Coronary heart disease; Double-Blind Method; drugs; General aspects; Genotype; Glycoproteins; Heart; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; lipids; lipoproteins; Male; Medical sciences; Middle Aged; Polymorphism, Genetic - genetics; Pravastatin - therapeutic use; Triglycerides - blood; CETP; Prognosis; Angiography; Cardiovascular disease; Lipids; Lipoprotein; Pravastatin; Vascular disease; Ester; Association; Atherosclerosis; Adult; Evolution; lipoproteins; Human; Drug; Radiodiagnosis; Enzyme; drugs; Enzyme inhibitor; Statin derivative; Concentration; Coronary heart disease; Protein; Medicine; Transfer; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2004.01281.x

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.