Abstract 13158: Lipoprotein-Associated Phospholipase A2 is Associated with Cardiovascular Mortality and Subclinical Atherosclerosis Phenotypes in African-Americans

Abstract

Introduction Lipoprotein-associated Phospholipase A2 (Lp-PLA2) is an enzyme that has been implicated to have a pro-atherogenic role in multiple studies, however, these studies predominantly included Caucasians. We examined the association of Lp-PLA2 with subclinical atherosclerosis phenotypes and cardiovascular (CV) mortality in the multi-ethnic Dallas Heart Study, focusing on African-Americans. Materials and Methods Lp-PLA2 mass and activity were measured in African-American and Caucasian subjects (n= 2609) from the Dallas Heart Study, a population-based cohort. Race-specific quartiles were constructed and analyzed using Cox-proportional hazards models to determine associations of Lp-PLA2 mass and activity to CV mortality. Linear regression was used to evaluate associations of these levels to the following subclinical atherosclerosis phenotypes: coronary artery calcium (CAC) measured by CT, and aortic plaque burden (APB) and aortic wall thickness (AWT) by abdominal MRI. Results The cohort (n=2609) consisted of 64% African Americans and 56% women with a mean age of 45 years, and mean Lp-PLA2 mass 191 ug/L and activity 145 umol/min/L. A total of 69 CV deaths occurred over a mean 8.2 years of follow up. Lp-PLA2 mass associated independently with CV mortality in the entire cohort (adjusted OR 2.2; 95% CI 1.4-3.6), as well as African-Americans alone (OR 2.1; 95% CI 1.3-3.6) (Table). Lp-PLA2 mass was also associated with CAC and AWT (P<0.001) in African-Americans (P<0.001). Although Lp-PLA2 activity was not statistically associated with CV mortality, it was associated with CAC in African-Americans. No relationship among Lp-PLA2 mass or activity and APB was demonstrated. Conclusions We extend previous findings reporting Lp-PLA2 mass associations with CV mortality and subclinical atherosclerosis to African-Americans. If Lp-PLA2 inhibitors in development are efficacious, they may clinically benefit not only Caucasians, but also African-Americans.