A prospective evaluation of lipoprotein-associated phospholipase A2 levels and the risk of future cardiovascular events in women

OBJECTIVES We sought to determine prospectively whether lipoprotein-associated phospholipase A2 (Lp-PLA2) was a predictor of future cardiovascular risk in women. BACKGROUND Inflammatory markers may help predict cardiovascular risk. Lp-PLA2 levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men. METHODS We conducted a prospective, nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease, non-fatal myocardial infarction, and stroke associated with baseline levels of Lp-PLA2 over a mean follow-up of three years. RESULTS In univariate analysis, mean levels of Lp-PLA2 correlated strongly with low-density lipoprotein cholesterol (r = 0.51; P = 0.0001), were lower among women currently using hormone replacement therapy (mean 0.98 mg/l vs. 1.23 mg/l; P = 0.0001) and were significantly higher at baseline among cases (n = 123) than controls (n = 123) (mean 1.20 mg/l vs. 1.05 mg/l; P = 0.016). However, the predictive value of Lp-PLA2 was markedly attenuated after adjustment for these and other cardiovascular risk factors. Specifically, the multivariate relative risks of future cardiovascular events for women in the lowest (referent) to highest quartiles of Lp-PLA2 were 1.00, 0.75, 0.64 and 1.17, respectively (all p values non-significant). In contrast, the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein (another marker of low-grade inflammation) were 1.00, 1.78, 2.02 and 4.66, respectively (p-value for TREND = 0.002). Inclusion of Lp-PLA2 levels did not significantly attenuate this latter observation. CONCLUSIONS In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA2 is not a strong predictor of future cardiovascular risk among unselected women.