Abstract 104: Serum from Patients with Aortic Valvular Stenosis Shows Decreased Cholesterol Efflux Capacities Despite Similar High-Density Lipoprotein Cholesterol Levels

Abstract

Background: Studies have shown that low HDL-cholesterol levels may be associated with the progression of aortic valvular calcium and aortic valvular stenosis (AVS), but whether patients with AVS have impaired cholesterol efflux capacities is unknown. Methods and results: We have measured four parameters of cholesterol efflux capacity in apolipoprotein B-depleted serum samples from 48 patients with (aortic jet velocity ≥2.5 m/s, mean age = 72 ± 7 years and 72.7% men) and 51 patients without AVS (aortic jet velocity ≤ 1.7 m/s, mean age 71 ± 7 years and 70.6% men). Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ABCA1 expression by cAMP (non-stimulated efflux, total efflux and ABCA1-mediated efflux), and HepG2 hepatocytes to measure SR-BI-mediated efflux. Mean HDL-cholesterol and apolipoprotein A-I levels as well as efflux are shown in the table for patients with vs. without AVS. The Pearson correlation coefficient between HDL-cholesterol levels and SR-B1-dependent efflux was 0.39 (p=0.007) in patients with AVS and 0.68 (<0.0001) in controls (P-value for the difference between the correlation coefficients obtained with Fisher’s test = 0.04). Conclusions: This study provides evidence that serum from patients with AVS may have impaired cholesterol efflux capacities, especially through the SR-B1 pathway. Table. Mean HDL-cholesterol and apolipoprotein A-I levels as well as non-stimulated-, total-, ABCA1-, and SR-B1-dependent cholesterol efflux obtained from patients’ serum with vs. without AVS. Data is shown as mean ± SD. Differences between categories were assessed using a Student unpaired t-test.