Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke - The Rotterdam Study

Background - Lipoprotein- associated phospholipase A2 ( Lp- PLA2) has been proposed as an inflammatory marker of cardiovascular disease. In the present study, we investigated whether Lp- PLA2 is an independent predictor of coronary heart disease and ischemic stroke. Methods and Results - The Rotterdam Study is a population- based follow- up study in 7983 subjects greater than or equal to 55 years of age. We performed a case- cohort study, including 308 coronary heart disease cases, 110 ischemic stroke cases, and a random sample of 1820 subjects. We used Cox proportional- hazard models with modification of the standard errors based on robust variance estimates to compute hazard ratios adjusted for age, sex, body mass index, systolic blood pressure, non- HDL cholesterol, HDL cholesterol, diabetes, smoking, alcohol consumption, cholesterol- lowering medication, white blood cell count, and C- reactive protein. Compared with the first quartile of Lp- PLA2 activity, multivariate-adjusted hazard ratios for coronary heart disease for the second, third, and fourth quartiles were 1.39 ( 95% CI, 0.92 to 2.10), 1.99 ( 95% CI, 1.32 to 3.00), and 1.97 ( 95% CI, 1.28 to 3.02), respectively ( P for trend = 0.01). Corresponding multivariate- adjusted hazard ratios for ischemic stroke were 1.08 ( 95% CI, 0.55 to 2.11), 1.58 ( 95% CI, 0.82 to 3.04), and 1.97 ( 95% CI, 1.03 to 3.79) ( P for trend = 0.03). The relation between Lp- PLA2 and coronary heart disease was present in both subjects with non- HDL cholesterol levels below the median and those with non- HDL cholesterol levels above the median. Conclusions - This study shows that Lp- PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population.