Cholesterol efflux capacity and arterial stiffness in healthy subjects: data from the brisighella heart study

Purpose: Serum capacity to promote cholesterol efflux from macrophages correlates inversely with carotid intima–media thickness and the likelihood of angiographic coronary artery disease, independently of the high density lipoprotein (HDL) level. We investigated the relationship between serum cholesterol efflux capacity and Pulse Wave Velocity (PWV), as an indicator of arterial stiffness, in healthy subjects. Methods: 99 subjects (40 males, 59 females) were selected from the Brisighella Heart Study cohort for being non-smokers, non-diabetics, untreated with antihypertensive, lipid-lowering or antidiabetic drugs, and without echographically detectable carotid atherosclerotic plaques. Serum cholesterol efflux capacity was measured as aqueous diffusion, total cholesterol efflux and ATP binding cassette A1 (ABCA1)-dependent cholesterol efflux (reflecting mainly HDL function). Bilateral B-mode carotid artery images for intima-media thickness were acquired using a linear phased multifrequency (7.5-10 MHz). The posterior wall of the distal common carotid artery, one centimeter below the bifurcation, was assessed as recommended by the international guidelines. An eltrectrocardiografic trace was used to acquire image frames only in end-diastole, avoiding IMT variation related to carotid pulsatility. Carotid-femoral PWV was measured with a high-fidelity tonometer. Results: In the unadjusted model, PWV relates directly with basal aqueous cholesterol diffusion (R= 0.224, P= 0.034) and indirectly with ABCA1-dependent cholesterol efflux (R= -0.215, P= 0.042). PWV does not correlate with total cholesterol efflux (R= 0.023, P= 0.830). In a stepwise multivariate analysis including age, body mass index, mean arterial pressure, serum low density lipoprotein level serum HDL level, ABCA1-dependent cholesterol efflux, aqueous diffusion, the best PWV predictors were mean arterial pressure (B= 0.83, 95%CI 0.058-0,108), age (B= 0.051, 95%CI 0.028-0.073) and ABCA1-dependent cholesterol efflux (B= -0.298, 95%CI -0.531- -0.066). Conclusions: ABCA1-dependent cholesterol efflux capacity, but not total serum HDL, is a significant predictor of PWV in healthy subjects. This finding points to the relevance of HDL function in vascular modeling and arterial stiffness prevention along life.