Clinical relevance of Lp-PLA₂

Lp‑PLA₂ (Lipoprotein-associated phospholipase A₂) - also known as platelet-activating factor acetylhydrolase (PAF-AH) - is a vascular-specific inflammatory enzyme, predominantly expressed by macrophages, lymphocytes and foam cells in atherosclerotic plaques. Circulating Lp‑PLA₂ is mainly associated with apolipoprotein B-containing lipoproteins, hence closely associated with low-density lipoprotein (LDL). The enzyme hydrolyzes oxidized phospholipids on LDL particles within the arterial intima, generating two highly inflammatory mediators, lysophosphatidylcholine (Lyso-PC) and oxidized non-esterified fatty acids (oxNEFAs).

Many important studies confirm a strong association between Lp‑PLA₂ levels and cardiovascular risk among different populations. These studies show that in individuals with normal LDL, elevated Lp‑PLA₂ levels were strongly associated with heart disease and ischemic stroke, independent of traditional risk markers and high-sensitive CRP. Due to the fact that Lp‑PLA₂ is involved in the causal pathway of plaque inflammation and plaque rupture, the testing for Lp‑PLA₂ represents a valuable adjunctive tool which goes beyond traditional cardiovascular risk assessment.

The importance of Lp-PLA₂ testing

It is well known, that inflammatory processes play an important role in the pathogenesis of atherosclerosis. Established risk factors account for part of the cardiovascular diseases only. Lp‑PLA₂, a new reliable marker in the atherosclerotic risk assessment, is able to close this diagnostic gap.

Studies provide strong evidence, that the presence of Lp‑PLA₂ is associated with an increased risk of cardiac death, myocardial infarction, acute coronary syndrome and ischemic stroke. Increased Lp‑PLA₂ concentrations can be found in vulnerable atherosclerotic plaques and allow discrimination between morphologically identical stable and unstable plaques. Lp‑PLA₂ testing is an excellent complement to angiography because it detects very small plaques not visible by medical imaging. Unlike traditional atherosclerotic risk markers Lp‑PLA₂ is highly specifc for vascular inflammation, has low biological variability, and plays a causative role in atherosclerotic plaque inflammation.