Abstract 2552: Lipoprotein-associated phospholipase A2 predicts atherosclerotic stroke risk: The Northern Manhattan Study

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has pro-inflammatory properties and may contribute to atherosclerosis, plaque rupture, and stroke. Lp-PLA2 levels may improve risk stratification, though whether this ability extends to all populations and stroke subtypes remains uncertain. We hypothesized that Lp-PLA2 levels would predict first ischemic stroke in a multiethnic, urban, population. Methods: Serum samples from stroke-free community participants in the Northern Manhattan Study were assayed using a microplate based ELISA to measure the mass concentration of Lp-PLA2 (PLAC Test, diaDexus, Inc). Participants were followed annually for stroke, and stroke subtype was determined according to the TOAST criteria. Cox proportional hazard models were fitted to estimate hazard ratios and 95% confidence intervals (HR, 95% CI) for the association of Lp-PLA2 mass levels with ischemic stroke, unadjusted and after adjusting for demographic, behavioral and medical risk factors. Results: Serum samples were available in 1946 participants with median follow up of 11 years; 151 subjects (7.8%) experienced a first ischemic stroke, of which 26 were large artery atherosclerotic strokes. Mean age was 69 (SD 10), 35.6% were men, 20% non-Hispanic Whites, 22% Blacks, and 55% Hispanics. The mean Lp-PLA2 level was 308.7 (SD 88.5) ng/mL. In non-Hispanic Whites, there was a trend toward increased risk of ischemic stroke with Lp-PLA2 levels (adjusted HR per SD 1.44, 95% CI 0.98-2.11), but not in Blacks (p for interaction with white=0.045); or in Hispanics (p for interaction with white=0.13). Lp-PLA2 levels were predictive of large artery atherosclerotic strokes (LAA) in the entire cohort (adjusted HR per SD 1.55, 95% CI 1.17-2.04). When analyzed by quartile, there were dose-response relationship with LAA (compared to the lowest quartile, 2nd quartile HR= 1.43, 95% CI 0.23-8.64; 3rd quartile HR=4.47, 95% CI 0.93-21.54; 4th quartile HR=5.07, 95% CI 1.07-24.06). When the analysis was stratified by race, Lp-PLA2 was associated with increased risk of LAA among whites, but not blacks or Hispanics (chi-squared 2 degrees of freedom, p for interaction=0.01). Conclusion: Lp-PLA2 was associated with risk of atherosclerotic stroke among non-Hispanic White participants, but not in other race-ethnic groups in the cohort. Further study is needed to confirm these race-ethnic differences and the reasons for them.