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Objective— Studies have shown that high-density lipoprotein (HDL)–raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL metabolism is unknown. Approach and Results— A total of 1435 single nucleotide polymorphisms in genes associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5, SCARB1, LIPC, CETP, LCAT, LIPG, APOC4 , and PLTP ) were genotyped in 382 patients with echocardiography-confirmed AVS (aortic jet velocity ≥2.5 m/s) and 401 controls. After control for multiple testing, none of the genetic variants showed a positive association with case/control status (adjusted P ≥0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre–β-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were measured in apolipoprotein B–depleted serum samples from 86 patients with and 86 patients without AVS. Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ATP-binding cassette A-1 expression by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1–mediated efflux. None of these parameters were different between cases and controls. However, compared with patients without coronary artery disease, sera from patients with coronary artery disease had lower HDL cholesterol levels, scavenger receptor class B type 1–mediated efflux, and HDL size ( P ≤0.003), independently of the presence or absence of AVS. Conclusions— Results of the present study suggest that, based on HDL genetics and HDL functionality, HDL metabolism does not seem to predict the risk of AVS. Because of our limited sample size, additional studies are needed to confirm these findings.

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 ( 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.