Lipoprotein-Associated Phospholipase A2 Mass and Activity and Risk of Cardiovascular Disease in a Population With High Prevalences of Obesity and Diabetes

Abstract

OBJECTIVE To investigate the association of lipoprotein-associated phospholipase A2 (LpPLA2) mass and activity with incident cardiovascular disease (CVD) in a population with high prevalences of insulin resistance and diabetes, conditions for which epidemiological data remain sparse. RESEARCH DESIGN AND METHODS We conducted a nested, case-control study (n = 1,008) within a population-based cohort of American Indians. Case subjects were defined by incidence of first-ever CVD up to 10 years later. Control subjects comprised participants free of CVD events during the follow-up period who were frequency matched to case subjects by age, sex, and diabetes status. LpPLA2 mass and activity were measured using commercially available assays. RESULTS LpPLA2 mass and activity were moderately correlated with each other (r = 0.30), but only LpPLA2 activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA2 measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA2 mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39–0.79]) and positive for LpPLA2 activity (highest versus lowest tertile, 1.65 [1.12–2.42]). These associations were similar when participants with and without diabetes were examined separately. CONCLUSIONS In this population-based cohort enriched with dysmetabolic phenotypes, LpPLA2 mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA2 mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA2 to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA2 mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.