Atherosclerosis manifests itself clinically at advanced stages when plaques undergo
hemorrhage and/or
rupture with superimposed
thrombosis, thus abruptly stopping blood supply. Identification of markers of plaque destabilization at a pre-clinical stage is, therefore, a major goal of cardiovascular research. Promising results along this line were provided by studies investigating the
lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of
phospholipase A2 proteins family that plays a key role in the metabolism of pro-inflammatory
phospholipids, as oxidized
low-density lipoproteins, and in the generation of pro-atherogenic metabolites, including
lysophosphatidylcholine and oxidized
free fatty acids. We herein review the experimental and clinical studies supporting use of
Lp-PLA2 activity for predicting cardiovascular events. To his end we considered not only
Lp-PLA2 activity and mass, but also
Lp-PLA2 gene variations and their association with incident
coronary artery disease,
stroke, and cardiovascular mortality. Based on these evidences the major scientific societies have included in their guidelines the measurement of
Lp-PLA2 activity among the
biomarkers that are useful in risk stratification of adult asymptomatic patients at intermediate cardiovascular risk. The results of two recently published major clinical trials with the
Lp-PLA2 inhibitor
darapladib, which seem to challenge the pathogenic role of
Lp-PLA2, will also be discussed.