BACKGROUND: The impact of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is a matter for ongoing debate. In this study, we analyse associations of CETP with cardiovascular endpoints in a cohort of patients with stable coronary artery disease (CAD). DESIGN: KAROLA is a prospective observational study of patients with CAD and a median follow-up of 8 years (n = 1132). CETP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Cholesteryl ester transfer protein levels were lower in men (P = 0.0016), positively correlated to low-density lipoprotein cholesterol, and inversely correlated to triglyceride levels (P < 0.0001 and P = 0.011 respectively). There was no significant difference in mortality between patients in different CETP quartiles; the hazard ratio of lowest vs. highest quartile was 1.33 (95% confidence interval (CI): 0.77-2.30) for mortality and 1.24 (95% CI: 0.75-2.03) for secondary events. In post hoc analyses, comparing nondiabetic subjects with CETP below vs. above median, the adjusted hazard ratio for death in patients with low CETP levels was 1.84 (95% CI: 1.10-3.09). CONCLUSION: Although statistically significant associations were found only in post hoc analyses, the effect sizes in this study were in line with previous findings in the Framingham and LURIC population. In combination, the emerging evidence challenges the concept of pharmacological CETP inhibition.
BACKGROUND: The impact of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is a matter for ongoing debate. In this study, we analyse associations of CETP with cardiovascular endpoints in a cohort of patients with stable coronary artery disease (CAD). DESIGN: KAROLA is a prospective observational study of patients with CAD and a median follow-up of 8 years (n = 1132). CETP levels were measured using an enzyme-linked immunosorbent assay. RESULTS:Cholesteryl ester transfer protein levels were lower in men (P = 0.0016), positively correlated to low-density lipoprotein cholesterol, and inversely correlated to triglyceride levels (P < 0.0001 and P = 0.011 respectively). There was no significant difference in mortality between patients in different CETP quartiles; the hazard ratio of lowest vs. highest quartile was 1.33 (95% confidence interval (CI): 0.77-2.30) for mortality and 1.24 (95% CI: 0.75-2.03) for secondary events. In post hoc analyses, comparing nondiabetic subjects with CETP below vs. above median, the adjusted hazard ratio for death in patients with low CETP levels was 1.84 (95% CI: 1.10-3.09). CONCLUSION: Although statistically significant associations were found only in post hoc analyses, the effect sizes in this study were in line with previous findings in the Framingham and LURIC population. In combination, the emerging evidence challenges the concept of pharmacological CETP inhibition.
Authors: Kristina Duwensee; Stefan Schwaiger; Ivan Tancevski; Kathrin Eller; Miranda van Eck; Patrick Markt; Tobias Linder; Ursula Stanzl; Andreas Ritsch; Josef R Patsch; Daniela Schuster; Hermann Stuppner; David Bernhard; Philipp Eller Journal: Atherosclerosis Date: 2011-07-21 Impact factor: 5.162