Abstract 1274: Serum Cholesterol Efflux Capacity, a Measure of HDL-C Quality, Varies According to Coronary Artery Disease Status Independently of HDL-C Quantity
Introduction: Although high-density lipoprotein cholesterol (HDL-C) levels are a powerful inverse predictor of coronary artery disease (CAD), HDL has remained a challenging therapeutic target. Emerging evidence suggests that variation in HDL functionality may relate to disease status and is potentially amenable to pharmacologic modulation.
Hypothesis: The ability of HDL to promote macrophage reverse cholesterol transport may mediate its atheroprotective role. As such, the capacity of human serum to accept cholesterol from macrophages may vary according to CAD status, potentially independent of HDL-C levels.
Methods: Serum cholesterol efflux capacity was measured in patients with (n=393) or without (n=302) angiographically confirmed CAD. Efflux capacity was quantified using a validated in vitro system that involved incubation of 2% apo-B depleted patient serum with cAMP treated J774 macrophage cells. A pooled serum control was used to normalize results across assays.
Results: HDL-C levels were a highly significant determinant of serum efflux capacity, but accounted for only 26% of the observed variation. Efflux capacity was significantly decreased in CAD patients in an adjusted model that included age, gender, and traditional cardiovascular risk factors (Mean±SE 12.5%±0.1 vs. 13.3%±0.2; p=0.0001). This difference was attenuated, but remained significant, after including HDL-C as an additional covariate (p=0.004). Binary logistic regression analysis indicated that efflux capacity was a strong independent predictor of CAD status both before (adjusted Odds Ratio (OR)/SD increase of efflux capacity = 0.71; p<0.0001) and after (OR/SD increase=0.74; p=0.002) inclusion of HDL-C levels in the model.
Conclusion: Serum cholesterol efflux capacity, a metric of HDL functionality, varies according to CAD status independently of HDL-C levels. Ongoing analyses will seek to identify common genetic polymorphisms and additional serum measurements that are predictive of efflux capacity. These data reinforce the concept that measurement of HDL quality, in addition to HDL quantity, may have utility in predicting cardiovascular risk and in the preclinical assessment of novel therapies seeking to enhance HDL metabolism.