ABSTRACT
OBJECTIVES: We sought to determine prospectively whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) was a predictor of future cardiovascular risk in women. BACKGROUND: Inflammatory markers may help predict cardiovascular risk. Lp-PLA(2) 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-PLA(2) over a mean follow-up of three years. RESULTS: In univariate analysis, mean levels of Lp-PLA(2) 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-PLA(2) 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-PLA(2) 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-PLA(2) levels did not significantly attenuate this latter observation. CONCLUSIONS: In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA(2) is not a strong predictor of future cardiovascular risk among unselected women.
