Lipoprotein-associated phospholipase A2: an independent predictor of cardiovascular risk and a novel target for immunomodulation therapy.

Cardiovascular disease (CVD) is the number one cause of death in both adult men and women. It is evident that active inflammation in the coronary arteries remains a key factor in plaque instability and subsequent cardiovascular events. The current clinical dilemma is that inflammation can occur even in patients who are on statin therapy, as well as in patients with "normal" cholesterol levels. Because fully half of all patients with cardiovascular events have normal cholesterol levels, there is a need to re-evaluate the role of inflammatory factors and biomarkers to better identify patients at risk. Current risk factors include C-reactive protein, fibrinogen, and platelet activator inhibitor-1. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is another emerging risk factor. The weight of evidence suggests that this biomarker also promotes vascular inflammation. Patients with higher levels of Lp-PLA2 have higher rates of CVD and stroke. Measurement of Lp-PLA2 can improve the identification of people at increased risk for CVD, independent of cholesterol, or C-reactive protein level. Lp-PLA2 has been an innovative target of immunomodulation therapy, and clinical studies with specific inhibitors are in progress evaluating this approach for both atherosclerosis development and clinical event reduction.