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Background: Mass levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), a leukocyte-derived enzyme involved in the metabolism of low-density lipoprotein to pro-inflammatory mediators, are associated with prognosis after stroke. Lp-PLA2 mass correlates only moderately with levels of Lp-PLA2 activity. The relationship of Lp-PLA2 activity to risk of stroke recurrence is unknown. We hypothesized that Lp-PLA2 activity levels would predict risk of recurrence. Methods: In the population-based Northern Manhattan Stroke Study, first ischemic stroke patients ≥40 years were followed for recurrent stroke. Levels of Lp-PLA2 activity were assessed in 467 patients, and categorized by quartile. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for risk of recurrent stroke associated with marker quartiles after adjusting for demographics, vascular risk factors, and high-sensitivity C-reactive protein (hsCRP). Results: Mean age was 68.9 ± 12.7 years; 54.6% were women; 53.3% Hispanic, 27.2% black, and 17.8% white. Median follow-up was 4.0 years, and there were 80 recurrent strokes. Compared to the lowest quartile of Lp-PLA2 activity, those in the highest had an increased risk of recurrent stroke (adjusted HR 2.54, 95% CI 1.01–6.39). Conclusion: Stroke patients withLp-PLA2 activity levels in the highest quartile, compared to those in the lowest quartile, had an increased risk of recurrence after first ischemic stroke. Further studies are warranted to determine whether this biomarker has clinical utility in determining high-risk populations of stroke survivors, and whether anti-inflammatory strategies that reduce levels of activity of Lp-PLA2 reduce the risk of stroke recurrence. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]