Review of the Evidence for the Clinical Utility of Lipoprotein-Associated Phospholipase A2 as a Cardiovascular Risk Marker

A substantial body of peer-reviewed studies has been published validating the role of inflammation in atherogenesis and supporting lipoprotein-associated phospholipase A2 (Lp-PLA2) as a cardiovascular risk marker independent of and additive to traditional risk factors. As with elevated high-sensitivity C-reactive protein, an elevated Lp-PLA2 level approximately doubles the risk for primary and secondary cardiovascular events. Interestingly, when both inflammatory markers are increased together, they provide an even greater predictive capability to help identify very-high-risk individuals who would benefit most from aggressive lipid-lowering therapy. High levels of Lp-PLA2 are present in inflamed, rupture-prone plaques, and it appears that Lp-PLA2 is released from these plaques into the circulation. Over 25 prospective epidemiologic studies have demonstrated the association of elevated Lp-PLA2 levels with future coronary events and stroke-11 of 12 prospective studies have shown a statistically significant association between elevated Lp-PLA2 and primary coronary or cardiovascular events, 12 of 13 have shown a statistically significant association with recurrent coronary or cardiovascular events, and 6 studies have shown a positive association with stroke. Lp-PLA2 should be viewed today as an important cardiovascular risk marker whose utility is as an adjunct to the major risk factors to adjust absolute risk status and thereby modify low-density lipoprotein cholesterol goals. The low biologic fluctuation and high vascular specificity of Lp-PLA2 makes it possible to use a single measurement in clinical decision making, and it also permits clinicians to follow the Lp-PLA2 marker serially. Ultimately, Lp-PLA2 may also be classified as a risk factor, but this should not detract from its utility today as a risk marker.