Clinical Utility of Lipoprotein-Associated Phospholipase A2 for Cardiovascular Disease Prediction in a Multiethnic Cohort of Women

Abstract

Abstract BACKGROUND Findings regarding the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and mass with incident cardiovascular disease (CVD) have been inconsistent, and their role in risk prediction is uncertain. METHODS A case–cohort sample from the Women's Health Initiative Observational Study (WHI-OS) comprised 1821 CVD cases and a reference subcohort of 1992 women. We used Cox regression models with inverse sampling weights to assess the association of Lp-PLA2 mass and activity with CVD (myocardial infarction, stroke, and CVD mortality). RESULTS Subcohort means were 184.3 mmol/min/mL for Lp-PLA2 activity and 499.2 μg/L for Lp-PLA2 mass, with 99% having mass above 200 μg/L, the clinically recommended cut point. Both activity and mass were positively associated with incident CVD in age- and race/ethnicity-adjusted analyses. Following adjustment according to CVD risk factors, the association with activity became null (hazard ratio = 1.02 for top vs bottom quartile, 95% CI = 0.79–1.33, P for trend = 0.65), but the association with mass remained (hazard ratio = 1.84, 95% CI = 1.45–2.34, P for trend < 0.0001). In contrast to blood pressure, HDL, and hsCRP, reclassification statistics for Lp-PLA2 mass did not suggest improvement for overall CVD after full adjustment. CONCLUSIONS In the WHI-OS Lp-PLA2 mass, but not activity, was independently associated with CVD. However, model fit did not significantly improve with Lp-PLA2 mass, and assay calibration remains a clinical concern.