SP479HDL CHOLESTEROL EFFLUX IS NOT PREDICTIVE OF CARDIOVASCULAR RISK IN DIABETIC PATIENTS ON HEMODIALYSIS

Abstract

Introduction and Aims: Cholesterol efflux capacity is a key cardioprotective HDL function and was shown to correlate inversely with cardiovascular outcomes in high-risk populations. Patients with end-stage renal disease (ESRD) harbor an exceptionally high cardiovascular risk, which cannot fully be explained by traditional risk factors. Here, we determined for the first time whether cholesterol efflux capacity is predictive of the cardiovascular risk in a hemodialysis population. Methods: In this post hoc analysis of the German Diabetes Dialysis study (4D study) HDL cholesterol efflux was measured in 1,147 hemodialysis patients with type 2 diabetes mellitus, who were randomly assigned to treatment with 20 mg atorvastatin daily or placebo. We quantified the efflux capacity by incubation of macrophages with apolipoprotein B depleted serum from the study participants and assessed the relation of cholesterol efflux with cardiovascular outcome. The primary endpoint was defined as a composite of cardiac death, nonfatal myocardial infarction and stroke; secondary endpoints were cardiac events and all-cause mortality. Results: In Cox regression analyses we found no association of efflux capacity with the primary endpoint (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.88 - 1.06, p=0.417), cardiac events (HR 0.92; 95% CI 0.83-1.02; p=0.108) or all-cause mortality (HR 0.96; 95% CI 0.88-1.05; p=0.390). Stratified subgroup analysis indicated a potential effect modification of atorvastatin on cardiac events. In patients with the lowest cholesterol efflux capacity atorvastatin reduced the risk for all cardiac Events (HR per 1 SD increase 0.66, 95% CI: 0.47-0.92, P=0.015), which remained significant following further adjustment with a number of relevant clinical parameters. Conclusions: In contrast to other high risk groups, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in diabetic patients on hemodialysis. Our data contribute to clarify the role of HDL in ESRD and advances our understanding of CVD in this high-risk population.