Oxidized phospholipids on plasminogen are associated with reduced platelet surface marker expression and intrinsic reactivity.

Elevated levels of oxidized phospholipids (OxPL) on plasminogen (OxPL-PLG) are associated with reduced time to fibrinolysis and reduced risk of cardiovascular events, but their effect on platelet function is unknown. We aimed to evaluate the association of OxPL-PLG with platelet surface marker expression, intrinsic and on‑dual anti-platelet (DAPT, aspirin plus clopidogrel)) platelet reactivity and cardiovascular events. OxPL-PLG levels were measured in pre-procedure blood samples in 2040 patients undergoing coronary angiography with or without PCI. The association of OxPL-PLG to pre-procedure and 24-hour platelet surface expression of CD62P, CD41 and PAC-1 and intrinsic and on-DAPT platelet reactivity in response to collagen and adenosine diphosphate (ADP) were assessed. The relationship of OxPL-PLG to myocardial infarction(MI)-free survival over a median 7-year follow-up was assessed using multivariable Cox regression models. Elevated levels of OxPL-PLG were significantly and inversely associated with age, male sex, severity of coronary obstruction, previous MI, PCI, and CABG. OxPL-PLG was inversely associated with platelet surface expression of CD41 (p < 0.001), CD62P (p = 0.0012) and PAC-1 (p < 0.001) at baseline and with CD41 (p = 0.001) and CD62P (p = 0.020) after DAPT. A significant inverse association was present between OxPL-PLG and intrinsic platelet reactivity in response to ADP (p < 0.001) at baseline but not after DAPT. OxPL-PLG was not associated with MI-free survival. In conclusion, elevated OxPL-PLG levels are independently associated with lower-risk clinical profile, less severe coronary disease, and reduced platelet activation and reactivity prior to DAPT. These findings suggest OxPL-PLG may modulate platelet activation and reactivity and warrant further mechanistic and clinical evaluation. EXCELSIOR study (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate; ClinicalTrials.gov Identifier: NCT00457236).