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

OBJECTIVE To investigate the association of lipoprotein-associated phospholipase A 2 (LpPLA 2 ) 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. LpPLA 2 mass and activity were measured using commercially available assays. RESULTS LpPLA 2 mass and activity were moderately correlated with each other ( r = 0.30), but only LpPLA 2 activity exhibited moderate correlations with lipid fractions. After extensive adjustment for covariates, both LpPLA 2 measures were significantly associated with incident CVD, but the relationship was inverse for LpPLA 2 mass (highest versus lowest tertile, relative risk [RR] 0.55 [95% CI 0.39–0.79]) and positive for LpPLA 2 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, LpPLA 2 mass and activity showed divergent associations with CVD. The inverse relationship for LpPLA 2 mass is contrary to observations from predominantly nondiabetic populations and will require independent replication. Whether this finding relates to redistribution of LpPLA 2 to lipoprotein classes where it is less atherogenic or reflects incomplete measurement of LpPLA 2 mass associated with altered lipoprotein composition in insulin resistance warrants further investigation.