One way to increase HDL cholesterol levels is to inhibit cholesteryl ester transfer protein (CETP). However, it has been suggested that its association with statins increases mortality, although the process by which this occurs remains unclear. This study performed a 10-year follow-up analysis in 812 patients (REGRESS cohort) with coronary artery disease treated with statins after an initial 2-year angiographic study period. Carriers of the TaqIB-B2 gene showed reduced CETP levels and high HDL cholesterol. Despite these lower CETP and higher HDL cholesterol concentrations, carriers of the B2 copy had hazard ratios of 1.59 (p=0.01) for atherosclerosis disease, 1.53 (p=0.03) for ischemic heart disease death, and 1.30 (p=0.04) for all-cause mortality. Because genetic variations associated with low CETP levels may be linked to increased risk, the efficacy of statin therapy to reduce cardiovascular risk might depend on CETP genotype and related levels. Because CETP is considered a promising target, these results may need to be considered in studies administering CETP inhibitors to patients with coronary heart disease. The paper was accompanied by an editorial written by Richard A. Lange and Merry L. Lindsey who highlighted the fact that the relationship between HDL cholesterol metabolism and cardiovascular disease is not fully understood. They underlined the fact that the study was not appropriately designed to conclude that the efficacy of statin therapy to reduce cardiovascular risk depends on CETP genotype. There was no control group because all patients were on statin therapy. Moreover, there were no diabetic patients in the study and it included only men. Therefore, further studies will be needed to understand why in some conditions increasing HDL cholesterol levels may not be cardioprotective.
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