Lipoprotein-Associated Phospholipase A2: An Independent Predictor of Coronary Artery Disease Events in Primary and Secondary Prevention

In recent years, atherosclerosis has become recognized as an inflammatory disease whose activity can be assessed by circulating biomarkers. Along with C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) may now be considered as a biomarker with sufficient accumulated evidence to support its application in clinical practice. Lp-PLA2 is especially appealing because of its vascular specificity, which directly derives from its role in plaque pathophysiology. This article reviews the highlights of the >25 prospective epidemiologic studies now published on Lp-PLA2 as a risk marker in primary or secondary prevention. These trials demonstrate generally consistent correlations between elevated Lp-PLA2 levels and the increased risk for cardiovascular events, even after multivariable adjustment for traditional risk factors, with roughly a doubling of risk associated with upper quantile levels. Furthermore, Lp-PLA2 as a risk predictor has been shown to be independent of and complementary to high-sensitivity CRP. These study results combined with recommendations from the American Heart Association/Centers for Disease Control (AHA/CDC) and the National Cholesterol Education Program III (NCEP III) suggest that Lp-PLA2 might best be used in current clinical practice to refine risk prediction in those at intermediate cardiovascular risk. An increasingly prevalent group at intermediate risk shown to benefit from Lp-PLA2 risk modification is the population with the cardiovascular metabolic syndrome, clinically identified as overweight patients with features of mixed dyslipidemia, dysglycemia, and hypertension. An additional application supported by these studies is further risk stratification of high- (often secondary-) risk patients into a group at very high risk, for whom a more aggressive target for low-density lipoprotein of <70 mg/dL (1 mg/dL = 0.02586 mmol/L) is now recommended as a reasonable therapeutic goal.