Very Low Serum Cholesterol Efflux Capacity is a Positive Predictor of Cardiovascular Risk, Independent of HDL-Cholesterol, Apolipoprotein A-I and HDL Particle Concentrations in the Montreal Heart Institute Biobank Cohort

Plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely associated with cardiovascular (CV) diseases. However, CV protection may derive from other characteristics of HDL, such as the cholesterol efflux capacity of serum HDL, the process by which HDL particles accept cholesterol from macrophages and other cell types. Cholesterol efflux capacity is inversely associated with CV risk and incident CV events. Our aim was to estimate CV risk in subjects with very low cholesterol efflux capacity and its relationship with HDL-related measures. To this end, cholesterol efflux capacity was measured with J774 macrophages in the basal state and after cAMP-stimulation and expressed as the ratio of control serum, for 1000 cases with previous myocardial infarction (MI) and 1000 healthy controls from the Montreal Heart Institute Biobank. Subjects with extreme efflux capacity were categorized as th percentile or u003e90 th percentile for each efflux variable. HDL particle concentration (HDL-P) was obtained from the NMR Lipoprofile, while the plasma LCAT and MPO concentrations were obtained by ELISA. Unadjusted odds ratios (OR) for MI were highly significant for efflux capacity th percentile with J774 cells in basal (OR=4.58, p th percentile was unaffected by individually adjusting for HDL-C (OR=4.86, p=0.0001), apoA-I (OR=3.76, p=0.0011), HDL-P (OR=3.23, p=0.0033), LCAT mass (OR=4.17, p th percentile with the J774 macrophage model have greatly increased CV risk, which is independent of both HDL mass and concentration and which reflects HDL dysfunction.