Abstract 427: Extreme Low Cholesterol Efflux Is Linked More Strongly To Worse Anti-oxidative Function Than With Systemic Inflammation

Abstract

Reverse cholesterol transport is a main anti-atherosclerotic function of high-density lipoprotein (HDL), and cholesterol efflux capacity (CEC) is a key first step of this function. Inflammation and oxidation are metabolically linked to cholesterol transport but the relationships between these functions have not been well characterized. The objective of this study was to determine if extreme high or low CEC also had differences in inflammation and anti-oxidative functions. We hypothesized that inflammation and anti-oxidative functions of HDL are worse in those with extreme low vs. high CEC. Cholesterol efflux capacity was previously measured in 2,924 participants in the Dallas Heart Study, a multi-ethnic population-based cohort. Those below the 10 th and above the 90 th percentile were recruited 15-17 years later, and those with persistent extreme high and low CEC were studied (N=36). Several inflammatory markers such as interleukin-1(IL-1), IL-6, IL-10, tumor necrosis factor α (TNF- α), vascular cell adhesion protein 1(VCAM-1), and serum amyloid A (SAA) were measured using MAGPIX instrument on whole EDTA plasma. The antioxidant levels of paraoxonase-1 (PON1) were measured based on arylesterase activity using ELISA kit on whole citrated plasma. We analyzed data in whole group and stratified by sex, race/ethnicity, and diabetes status. Despite a two-fold difference in CEC, there were no significant differences in inflammatory markers between extreme high vs. low CEC. In those with diabetes, SAA levels were significantly higher in those with low vs. high efflux (P=0.02). High CEC group showed the inverse association with inflammatory marker (IL-1) while direct association with anti-inflammatory marker (IL-10) performing Pearson Correlation Coefficient, R=1, P<0.0001. Activity of PON1 was lower in those with extreme low vs. high CEC, median (IQR) low vs. high: 76.7 (62.2-104.5) vs. 90.1 (82.6-102.0) U/L, (P=0.03). In conclusion, these findings suggest that a key measure of reverse cholesterol transport is more strongly related to anti-Oxidative function than systemic inflammation. Future studies are warranted to determine the complementary information these metabolic markers contribute for cardiovascular risk.