INTRODUCTION: High platelet reactivity (HPR) on dual antiplatelet therapy is a risk factor for adverse vascular events in acute coronary syndrome (ACS) patients. Several studies have shown that reactive oxygen species (ROS) may be involved in modulating platelet function. METHODS: In Non-ST elevation myocardial infarction (NSTEMI) patients (n = 132) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy blood samples were collected within 24 h from 600 mg clopidogrel loading dose. Platelet reactivity was assessed by light transmission aggregometry using 10 μM ADP, 1 mM arachidonic acid (AA) and 2 μg/ml collagen. ROS production and lipoperoxidation of circulating cells were determined. by FACSCanto flow cytometry. In these patients, we investigated: 1) the relationship between the amount of cellular ROS production/lipoperoxidation and platelet reactivity; 2) the association of cellular ROS production with the presence of high platelet reactivity to ADP and arachidonic acid (AA). RESULTS: Significantly higher levels of platelet and leukocyte-derived ROS were detected in 49 dual HPR (with platelet aggregation by AA ≥ 20% and by ADP ≥ 70%) compared to non-HPR patients (n = 49) [Platelet-derived ROS: +142%; Leukocyte-derived ROS: +14%, p < 0.0001]. Similarly, dual HPR patients had significantly higher platelet and leukocyte lipoperoxidation than non-HPR patients [Platelet lipoperoxidation: +131%; Leukocyte lipoperoxidation: +14%, p < 0.001]. After adjustment for several potential confounders, platelet-, leukocyte-derived ROS and platelet and leukocyte lipoperoxidation remained significantly associated to dual HPR. The significant predictors of ADP, AA, and collagen platelet aggregation at multiple linear regression analysis, after adjusting for age, cardiovascular risk factors, procedural parameter, medications, leukocyte number and MPV, were platelet-, leukocyte-derived ROS and platelet and leukocyte lipoperoxidation (p < 001). CONCLUSIONS: Our results demonstrate that in NSTEMI patients on dual antiplatelet therapy, ROS production by and lipoperoxidation of platelets are strictly correlated to the different pathways of platelet aggregation and that ROS production and lipoperoxidation of platelets and leukocytes are predictors of non responsiveness to dual antiplatelet treatment.
INTRODUCTION: High platelet reactivity (HPR) on dual antiplatelet therapy is a risk factor for adverse vascular events in acute coronary syndrome (ACS) patients. Several studies have shown that reactive oxygen species (ROS) may be involved in modulating platelet function. METHODS: In Non-ST elevation myocardial infarction (NSTEMI) patients (n = 132) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy blood samples were collected within 24 h from 600 mg clopidogrel loading dose. Platelet reactivity was assessed by light transmission aggregometry using 10 μM ADP, 1 mM arachidonic acid (AA) and 2 μg/ml collagen. ROS production and lipoperoxidation of circulating cells were determined. by FACSCanto flow cytometry. In these patients, we investigated: 1) the relationship between the amount of cellular ROS production/lipoperoxidation and platelet reactivity; 2) the association of cellular ROS production with the presence of high platelet reactivity to ADP and arachidonic acid (AA). RESULTS: Significantly higher levels of platelet and leukocyte-derived ROS were detected in 49 dual HPR (with platelet aggregation by AA ≥ 20% and by ADP ≥ 70%) compared to non-HPR patients (n = 49) [Platelet-derived ROS: +142%; Leukocyte-derived ROS: +14%, p < 0.0001]. Similarly, dual HPR patients had significantly higher platelet and leukocyte lipoperoxidation than non-HPR patients [Platelet lipoperoxidation: +131%; Leukocyte lipoperoxidation: +14%, p < 0.001]. After adjustment for several potential confounders, platelet-, leukocyte-derived ROS and platelet and leukocyte lipoperoxidation remained significantly associated to dual HPR. The significant predictors of ADP, AA, and collagen platelet aggregation at multiple linear regression analysis, after adjusting for age, cardiovascular risk factors, procedural parameter, medications, leukocyte number and MPV, were platelet-, leukocyte-derived ROS and platelet and leukocyte lipoperoxidation (p < 001). CONCLUSIONS: Our results demonstrate that in NSTEMI patients on dual antiplatelet therapy, ROS production by and lipoperoxidation of platelets are strictly correlated to the different pathways of platelet aggregation and that ROS production and lipoperoxidation of platelets and leukocytes are predictors of non responsiveness to dual antiplatelet treatment.
Authors: M Verdoia; A Schaffer; L Barbieri; G Di Giovine; G Bellomo; P Marino; H Suryapranata; G De Luca Journal: Neth Heart J Date: 2016-07 Impact factor: 2.380
Authors: Nina W van der Hoeven; Gladys N Janssens; Henk Everaars; Alexander Nap; Jorrit S Lemkes; Guus A de Waard; Peter M van de Ven; Albert C van Rossum; Javier Escaned; Hernan Mejia-Renteria; Tim J F Ten Cate; Jan J Piek; Clemens von Birgelen; Marco Valgimigli; Roberto Diletti; Niels P Riksen; Nicolas M Van Mieghem; Robin Nijveldt; Maarten A H van Leeuwen; Niels van Royen Journal: J Am Heart Assoc Date: 2020-03-03 Impact factor: 5.501