A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women

Objectives We sought to determine prospectively whether lipoprotein-associa ted phospholipase A(2) (Lp-PLA(2)) was a predictor of future cardiovascular risk in women. Background Inflammatory markers may help predict cardiovascular risk. Lp-PL A(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 coron ary heart disease, non-fatal myocardial infarction, and stroke associated w ith 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 strongl y with low-density lipoprotein cholesterol (r=0.51; p=0.0001), were lower a mong 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). Howe ver, the predictive value of Lp-PLA(2) was markedly attenuated after adjust ment for these and other cardiovascular risk factors. Specifically, the mul tivariate relative risks of future cardiovascular events for women in the l owest (referent) to highest quartiles of Lp-PLA(2) were 1.00, 0.75, 0.64 an d 1.17, respectively (all p values non-significant). In contrast, the adjus ted relative risks of future cardiovascular events for each increasing quar tile 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). Inclus ion of Lp-PLA(2) levels did not significantly attenuate this latter observa tion. Conclusions In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA(2) is not a strong predictor of future cardiovasc ular risk among unselected women. (J Am Coll Cardiol 2001;38:1302-6) (C) 20 01 by the American College of Cardiology.