Cited 64 times since 2008 (4.1 per year) source: EuropePMC European heart journal, Volume 29, Issue 22, 28 4 2008, Pages 2792-2799 CETP genotype predicts increased mortality in statin-treated men with proven cardiovascular disease: an adverse pharmacogenetic interaction. Regieli JJ, Jukema JW, Grobbee DE, Kastelein JJ, Kuivenhoven JA, Zwinderman AH, van der Graaf Y, Bots ML, Doevendans PA
Aims
Inhibition of cholesteryl ester transfer protein (CETP) increases HDL-cholesterol. However, its combination with statins may increase mortality by factors incompletely understood. We previously observed that patients with intrinsically low CETP levels (carriers of the TaqIB-B2 allele) may have less benefit from statin therapy, and here tested this pharmacogenetic hypothesis on long-term outcomes.
Methods and results
We performed a 10-year follow-up analysis in 812 coronary artery disease (CAD) patients (REGRESS cohort), treated with statins after an initial 2-year study period. Carriers of TaqIB-B2 showed reduced CETP levels and higher HDL-cholesterol (P < 0.001 for both). Despite these lower CETP and higher HDL-cholesterol levels, hazard ratios per B2 copy were 1.59 (P = 0.01) for atherosclerotic disease death, 1.53 (P = 0.03) for ischaemic heart disease death, and 1.30 (P = 0.04) for all-cause mortality. Haplotype-effects analysis provided even stronger basis for the genetics involved: one risk-haplotype was identified that was highly significantly associated with these endpoints.
Conclusion
In statin-treated male CAD patients, genetic variation conferring low CETP levels is associated with increased 10-year mortality. This suggests that efficacy of statin therapy to reduce cardiovascular risk depends on CETP genotype and associated CETP plasma levels. This effect may need consideration when administering CETP inhibition to CAD patients.
