Abstract 19753: Hdl Cholesterol Efflux Capacity is Inversely Associated With Incident Chd Events Independent of Hdl-c and Apoa-i Concentrations

Background: Although plasma HDL-C levels are strongly associated with risk of coronary heart disease (CHD), interventions that raise HDL-C have not been shown to reduce CHD risk. A prototypical measure of HDL function, namely HDL cholesterol efflux capacity, has been shown to be associated with prevalent CHD even after adjusting for HDL-C, but its association with incident CHD events remains uncertain. Methods: We measured HDL cholesterol efflux capacity and assessed its relationship to incident CHD events in a nested case control sample within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40-79 years examined in 1993-1997 and followed up to 2009. We quantified efflux capacity in 1895 incident CHD cases and 2474 control participants free of any cardiovascular disorders, by using a validated ex-vivo radiotracer assay that involved incubation of J774 macrophages with apoB-depleted serum from the study participants. Results: HDL cholesterol efflux capacity was positively correlated with HDL-C levels (r2=0.27; P-value<5x10-5) and apoA-I (r2=0.24;P-value< 5x10-5). In analyses comparing top versus bottom third, cholesterol efflux capacity was significantly inversely associated with incident CHD, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist-to-hip ratio, BMI, LDL-C levels and even after controlling for HDL-C or apoA-I (OR: 0.75 [0.53, 0.97];P-value:9.1x10-3) (Figure). Conclusions: HDL cholesterol efflux capacity is significantly and inversely associated with incident CHD events, independent of established vascular risk factors and after adjusting for HDL-C and apoA-I levels.