Oxidized phospholipids on plasminogen influence platelet activation and reactivity

A. Kille (Bad Krozingen)¹, K. Kaier (Freiburg im Breisgau)², T. Nührenberg (Bad Krozingen)³, K. Franke (Bad Krozingen)³, C. M. Valina (Bad Krozingen)³, X. Yang (La Jolla)⁴, G. Leibundgut (Basel)⁵, F.-J. Neumann (Bad Krozingen)¹, D. Westermann (Freiburg im Breisgau)⁶, W. Hochholzer (Würzburg)⁷, S. Tsimikas (La Jolla)^4
1Universitäts-Herzzentrum Freiburg / Bad Krozingen Klinik für Kardiologie und Angiologie Bad Krozingen, Deutschland; ²Universitätsklinikum Freiburg Institut für Medizinische Biometrie und Statistik Freiburg im Breisgau, Deutschland; ³Universitäts-Herzzentrum Freiburg / Bad Krozingen Klinik für Kardiologie und Angiologie II Bad Krozingen, Deutschland; ⁴University of California Vascular Medicine Program, Sulpizio Cardiovascular Center La Jolla, USA; ⁵Universitätsspital Basel Abt. für Kardiologie Basel, Schweiz; ⁶Universitäts-Herzzentrum Freiburg - Bad Krozingen Innere Medizin III, Kardiologie und Angiologie Freiburg im Breisgau, Deutschland; ⁷Klinikum Würzburg Mitte gGmbH Kardiologie & Internistische Intensivmedizin Würzburg, Deutschland

Background: Oxidized phospholipids (OxPL) on plasminogen (OxPL-PLG) are associated with reduced time to fibrinolysis and lower risk of cardiovascular outcomes, but it is not known if they influence platelet function.

Objectives: To evaluate the association of OxPL-PLG with intrinsic and on‑clopidogrel platelet reactivity and long-term cardiovascular events.

Methods: OxPL-PLG was measured in 2040 patients undergoing elective coronary angiography with or without percutaneous coronary angiography (PCI) if indicated in the EXCELSIOR trial. The association of OxPL-PLG to intrinsic and on-clopidogrel platelet reactivity and platelet surface expression of CD62P, CD41 and PAC-1 levels and to myocardial infarction(MI)-free survival and all-cause mortality at a median of 7 years using multivariable Cox regression models was determined.

Results: Elevated levels of OxPL-PLG were inversely and significantly associated with age, male sex, previous MI, PCI, and CABG, and positively will LDL-C, hypertension and obesity, plasminogen levels, platelet count and higher LV function. A significant association were present between OxPL-PLG and intrinsic platelet reactivity in response to ADP (p<0.001) but not collagen (p=0.085). OxPL-PLG was inversely and significantly associated with CD41 (p<0.001), CD62P (p<0.001), PAC-1 (p<0.001) platelet surface expression at baseline and with CD41 (p<0.001), CD62P (p=0.020), after 24 hours but not PAC-1 (p=0.058), p-values for linear relationship. OxPL-PLG and plasminogen were not associated with all-cause of MI-free survival at median 7-year follow-up.