The reduction of elevated low-density lipoprotein cholesterol (LDL-c) and mainly dense LDL, is the main target in reducing CHR closely associated with coronary heart disease (CHD). The findings of epidemiological and clinical investigations have, however, revealed that it poses a cardiovascular risk in only half of CHD patients and that a more effective marker is required. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker which provides information on plaque inflammation and stability. It hydrolyzes oxidized phospholipids, resulting in lysophosphatidylcholine, which is pro-inflammatory in a theoretic plaque. It is an enzyme that is expressed in macrophages and foam cells in rupture-prone atherosclerotic plaque. In plasma, 80% of it is attached to LDL and 20% to HDL. Twenty five epidemiological studies have established that Lp-PLA2 is a unique biomarker that is highly vascular-specific and that it is directly related to plaque instability and rupture. The results of a meta-analysis of 20,000 patients established a high relative risk for cardiovascular events in patients with high Lp-PLA2 Levels. Data from epidemiological studies have shown that Lp-PLA2 is a risk factor for primary and secondary ischemic stroke. Studies on drapalib, which is a direct inhibitor of Lp-PLA2, have shown that Lp-PLA2 prevents necrotic core progression and reduces plaque inflammation. Patients who are at moderate or high risk of CHD, and who have high levels of Lp-PLA2, should be considered as high and very high risk, respectively, and receive the appropriate treatment.