Oxidized phospholipids in cardiovascular disease

Prolonged or excessive exposure to oxidized phospholipids (OxPLs) generates chronic inflammation. OxPLs are present in atherosclerotic lesions and can be detected in plasma on apolipoprotein B (apoB)-containing lipoproteins. When initially conceptualized, OxPL-apoB measurement in plasma was expected to reflect the concentration of minimally oxidized LDL, but, surprisingly, it correlated more strongly with plasma lipoprotein(a) (Lp(a)) levels. Indeed, experimental and clinical studies show that Lp(a) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins. Plasma OxPL-apoB levels provide diagnostic information on the presence and extent of atherosclerosis and improve the prognostication of peripheral artery disease and first and recurrent myocardial infarction and stroke. The addition of OxPL-apoB measurements to traditional cardiovascular risk factors improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful. Moreover, plasma OxPL-apoB levels predict cardiovascular events with similar or greater accuracy than plasma Lp(a) levels, probably because this measurement reflects both the genetics of elevated Lp(a) levels and the generalized or localized oxidation that modifies apoB-containing lipoproteins and leads to inflammation. Plasma OxPL-apoB levels are reduced by Lp(a)-lowering therapy with antisense oligonucleotides and by lipoprotein apheresis, niacin therapy and bariatric surgery. In this Review, we discuss the role of role OxPLs in the pathophysiology of atherosclerosis and Lp(a) atherogenicity, and the use of OxPL-apoB measurement for improving prognosis, risk reclassification and therapeutic interventions. In this Review, Tsimikas and Witztum discuss the role of oxidized phospholipids (OxPLs) in atherosclerosis, describe the methods for measuring OxPLs on apolipoprotein B-containing lipoproteins (OxPL-apoB) and their relationship with lipoprotein(a), and discuss the clinical applications of the OxPL-apoB measurement for improving diagnosis, prognosis, risk reclassification and therapeutic interventions in patients with atherosclerotic cardiovascular disease. Phosphocholine-containing oxidized phospholipids (OxPLs) induce chronic inflammation, including in atherosclerotic lesions, and can be detected in plasma on apolipoprotein B-100 (apoB-100)-containing lipoproteins.A method has been developed to quantify OxPLs on a normalized amount of apoB-100 (OxPL-apoB), so that the measurement is independent of plasma apoB-100 and LDL cholesterol levels.Lipoprotein(a) (Lp(a)) particles carry the largest fraction of OxPLs among apoB-containing lipoproteins; the OxPLs are bound covalently to apolipoprotein(a) and are free in the lipid phase of the associated LDL-like particle.Plasma OxPL-apoB levels predict the presence and extent of anatomical atherosclerotic cardiovascular disease, and elevated levels are associated with disease in multiple arterial beds; measurement of OxPL-apoB improves prognostication of peripheral artery disease, as well as incident and recurrent myocardial infarction and stroke, and improves risk reclassification, particularly in patients in intermediate risk categories, for whom improving decision-making is most impactful.Plasma OxPL-apoB levels are reduced by treatment with antisense oligonucleotides aimed at reducing Lp(a) production and by lipoprotein apheresis, niacin therapy and bariatric surgery.Plasma OxPL-apoB levels predict cardiovascular events with a potency similar to or greater than that of plasma Lp(a) levels, probably because OxPL-apoB levels reflect the levels of the most atherogenic and pro-inflammatory Lp(a) and apoB-100-containing particles.