Aims. A key function of high-density lipoprotein (HDL) particles in cardiovascular protection is cholesterol efflux, the removal of cholesterol from macrophage foam cells and first step in reverse cholesterol transport. This study prospectively investigated whether HDL cholesterol efflux capacity is associated with cardiovascular mortality, all-cause mortality, and graft failure in renal transplant recipients, patients with accelerated atherosclerosis formation. Methods and Results. In renal transplant recipients (n=495, median follow-up 7.0 years) cholesterol efflux capacity at baseline was quantified using incubation of human macrophage foam cells with apolipoprotein B-depleted plasma. Baseline efflux capacity was not different in deceased patients compared to survivors (P=0.60 or P=0.50 for cardiovascular or all-cause mortality, respectively), whereas recipients developing graft failure had lower efflux capacity than those with functioning grafts (P<0.001). Kaplan-Meier analysis demonstrated a lower risk for graft failure (P=0.004), but not cardiovascular (P=0.30) or all-cause mortality (P=0.31), with increasing gender-stratified tertiles of efflux capacity. Cox regression analyses adjusted for age and gender showed that efflux capacity was not associated with cardiovascular mortality (hazard ratio [HR]=0.891 [0.668-1.188], P=0.43); the association between efflux capacity and all-cause mortality (HR=0.786 [0.631-0.978], P=0.031) disappeared after further adjustment for potential confounders. However, efflux capacity at baseline significantly predicted graft failure (HR=0.433 [0.291-0.644], P<0.001), independent of apolipoprotein A-I, HDL cholesterol, or creatinine clearance. Conclusion. This prospective study demonstrates that cholesterol efflux capacity from macrophage foam cells is not associated with cardiovascular or all-cause mortality, but is a strong predictor of graft failure independent of plasma HDL cholesterol levels in renal transplant recipients.


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