Do elevated Lp-PLA2 activity and myeloperoxidase indicate vessel wall inflammation and vulnerable plaque?

Vascular inflammation is a key driver of atherosclerotic progression and acute cardiovascular events. Elevated levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and myeloperoxidase (MPO) serve as highly specific, localized indicators of active inflammatory processes within the vessel wall.

Mechanistic pathways of vascular inflammation

• Synergistic lipid oxidation: Myeloperoxidase, released by activated neutrophils and macrophages in atherosclerotic lesions, generates reactive chlorinating species that oxidize lipid substrates. This accumulation of oxidized phosphatidylcholine directly promotes the enzymatic activity of Lp-PLA2.
• Plaque destabilization: Lp-PLA2 hydrolyzes these oxidized lipids to generate lysophosphatidylcholine, driving monocyte recruitment and endothelial dysfunction. Simultaneously, MPO-driven matrix degradation and collagen cleavage actively weaken the plaque's structural integrity, promoting macrophage apoptosis and necrotic core expansion.

Plaque instability and clinical risk

• Vulnerable plaque biology: This localized inflammation directly drives vulnerable plaque features, including thin-cap fibroatheromas (TCFAs), intraplaque hemorrhage (IPH), and large lipid-rich necrotic cores (LRNC).
• Elevated stroke risk: In the carotid arteries, MRI-defined IPH increases the hazard of an ipsilateral ischemic stroke or TIA by 2- to 11-fold, a large LRNC triples the risk, and fibrous cap rupture raises clinical risk 5- to 6-fold.
• Elevated myocardial infarction risk: In coronary vessels, these same features of plaque instability correlate with a 2- to 8-fold increase in lesion-specific major adverse cardiac events and myocardial infarction.

Bottom line

• Elevated Lp-PLA2 and MPO are direct, complementary biomarkers of vessel wall inflammation that mechanically drive vulnerable plaque biology, leading to plaque instability and an up to 11-fold higher risk of heart attack and stroke.