Abstract 391: Low Levels of CETP and Cardiovascular Disease Risk: A 10 Year Follow-Up Study in Statin Treated Patients with Ischemic Heart Disease
INTODUCTION Inhibitors of cholesteryl ester transfer protein (CETP) raise HDL-C. Findings of increased mortality when using a CETP inhibitor on top of a statin (ILLUMINATE) have questioned this approach to reduce cardiovascular risk. Statins also reduce CETP albeit to a moderate extent. We previously provided evidence that CAD patients carrying a CETP gene variant which is associated with low CETP do not benefit from statins. Hypothesizing that reducing CETP in patients with endogenous low CETP may have adverse effects we studied the impact of a common CETP gene variant on 10-year outcomes among statin-treated patients.
METHODS Data obtained originated from a ten-year follow-up on mortality and morbidity in the REGRESS trial cohort comprising 884 male CAD patients genotyped for the CETP TaqIB variant. Risks of outcome events were estimated by Proportional Hazards, according to co-dominant inheritance of CETP genotype.
RESULTS The B2 allele (frequency 0.399) was associated with reduced CETP and higher HDL-C (p<0.001 for both). Counter intuitively, hazard ratios per each added B2 copy were 1.60 (95% CI 1.12–2.29; p=0.01) for all vascular related death (KM figure⇓), 1.39 (1.04–1.84; p=0.02) for non-fatal MI+IHD death, and 1.30 (1.01–1.66; p=0.04) for all-cause mortality, respectively.
CONCLUSION In statin-treated male CAD patients, the B2 allele is associated with increased 10-year cardiovascular risk. This observation may mimick the situation in patients using a CETP inhibitor on top of statin therapy. The results suggest that the efficacy of statin therapy in patients might depend on endogenous CETP levels. This may need to be accounted for when lowering CETP using statins.