Abstract 14144: Decreased Efflux Capacity in Patients with Low CETP Plasma Levels

Abstract

Introduction: CETP has been considered as a possible target for treatment of cardiovascular disease. However, first clinical studies employing CETP inhibitors have failed to demonstrate clinical benefit. Additionally, we have previously shown that low endogenous plasma levels of CETP are associated with increased mortality in CAD patients. We hypothesized, that low CETP plasma levels are associated with decreased HDL function.

Methods: Serum HDL efflux capacity was measured in 154 patients of the Ludwighshafen Risk and Cardiovascular Health (LURIC) study displaying extremely low (< 0.68 μ g/ml, n = 77) or high (> 2.13 μ g/ml, n = 77) CETP concentrations in their plasma, respectively. Patients were referred to coronary angiography at baseline. Median follow-up time was 7.75 years. Primary and secondary endpoints were cardiovascular and all-cause mortality, respectively.

Results: We found increased levels of HDL-cholesterol and Apo-AI in the fourth quartile of HDL efflux capacity. No differences were found concerning other lipoprotein parameters including triglycerides, LDL-cholesterol, VLDL-cholesterol and ApoB. After adjustment for age, sex and HDL-cholesterol, hazard ratios for overall and cardiovascular death were lower in the second and third efflux quartile when compared to quartiles 1 and 4, pointing toward a U-shaped association between serum HDL efflux and mortality. In addition, serum HDL efflux capacity was lower in low CETP patients when compared to high CETP patients (15.1 ± 1.75 versus 15.96 ± 2.51 µg/ml, p = 0.015).

Conclusion: Decreased serum HDL efflux capacity might at least partially explain the observed increased mortality in patients with low CETP concentration as well as in patients treated with CETP inhibitors, which is again questioning the rationale of CETP inhibition for treatment of arteriosclerosis in coronary artery disease patients.