Abstract 388: High-density Lipoprotein Cholesterol Efflux Capacity is not associated with Atherosclerosis and Cardiovascular Events: the CODAM Study

Abstract

Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, its role in atherosclerosis risk is still controversial. In this study, we have analyzed the relationship between HDL CEC and atherosclerosis surrogates (carotid intima media thickness (cIMT), endothelial dysfunction (EnD); Z-Scores) in a well-characterized clinical population in the Cohort of Diabetes and Atherosclerosis Maastricht (CODAM) study, which consists of 574 individuals (age 59.6±0.3yrs, 61.3% men, 24.4% T2DM). Multiple linear regression analyses were performed to identify the associations in baseline data between HDL CEC (%), plasma HDL cholesterol (HDL-C, mmol/L), HDL size (nm), apoprotein A1 (ApoA1, g/L), and HDL Particle Concentration (HDL-P, nmol/L (LN), by NMR) with cIMT and EnD. Logistic regression analyses were done to identify the association of the above-mentioned HDL characteristics and CV events (CVE; N=499, 80 CVE cases). Analyses were adjusted for lifestyle, medication and metabolic confounders. The results show that HDL-C (ß=-0.65, 95%CI -0.91; -0.42), HDL size (ß=-0.57, 95%CI -0.98; -0.15), apoA1 (ß=-0.65, 96%CI -1.01; -0.29), and HDL-P (ß=-0.77, 95%CI -1.47; -0.11) were inversely associated with EnD (N=532), whereas HDL CEC was not (ß=-0.03, 95%CI=-0.24;0.24). Interestingly, preliminary analyses show that these associations are lost in diabetic subjects (N=131), but not in non-diabetics (N=401). An inverse association also exists between HDL-C, HDL size, apoA1, and HDL-P with cIMT (N=494), which was not statistically significant likely due to variability and relative insensitivity of cIMT measurements. Further, a 1 unit increase of HDL-C was associated with ~4fold lower prevalence of CVE (OR=0.25, 95%CI 0.08;0.83), and for HDL-P, with ~20fold less CVE (OR=0.05, 95%CI 0.00;0.70), but no association was found between HDL CEC and CVE (OR=1.26, 95%CI 0.41;3.84). Our results show that certain HDL-related parameters have atheroprotective associations, but HDL-CEC is not one of them. This result agrees with, but differs from, some other studies, and might reflect population differences in the relationships between measurements of HDL lipids/particle number, and HDL CEC.