Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Does high serum uric acid level cause aspirin resistance? Bekir S. Yildiz a , Emel Ozkan b , Fatma Esin b , Yusuf I. Alihanoglu a , Hayrettin Ozkan c , Murat Bilgin d , Ismail D. Kilic a , Ahmet Ergin e , Havane A. Kaftan a and Harun Evrengul a In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high- sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage. Blood Coagul Fibrinolysis 27:412–418 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. Blood Coagulation and Fibrinolysis 2016, 27:412–418 Keywords: aspirin resistance, coronary artery disease, serum uric acid level, trombocyte a Department of Cardiology, Pamukkale University, Denizli, b Izmir Ataturk Training and Research Hospital, c Izmir Bozyaka Training and Research Hospital, Izmir, d Department of Cardiology, Dıskapı Training and Research Hospital, Ankara and e Department of Public Health, Pamukkale University, Denizli, Turkey Correspondence to Bekir S. Yildiz, MD, Medical Faculty, Department of Cardiology, Pamukkale University, Denizli, 20100, Turkey Tel: +90 536 2195263; fax: +90 0258 213 4922; e-mail: byildiz@pau.edu.tr/bserhatyildiz@yahoo.com Received 23 August 2015 Revised 22 September 2015 Accepted 26 September 2015 Introduction Serum uric acid (SUA) level is frequently elevated in individuals with coronary artery disease (CAD) and has been proposed as a biomarker of CAD [1]. Studies in different populations at high risk of cardiovascular dis- ease (CVD) have shown a relationship between SUA and CVD mortality [2 – 5]. Increased SUA, the final product of purine metabolism in humans, is also associated with hypertension, endothelial dysfunction, and systemic inflammation [6–8]. SUA stimulates angiotensin 2 pro- duction, vascular smooth muscle cell proliferation, and oxidative stress in vascular smooth muscle cell through tissue of the renin-angiotensin system, as well as, activates mitogen-activated protein kinases, local throm- boxane formation, and platelet-derived growth factor A [9,10]. At low dosages, aspirin acts as an antiplatelet agent that can reduce cardiovascular complications in high-risk patients [11,12]. Some patients, however, do not respond properly to aspirin during aspirin therapy for secondary prevention as part of a situation known as ‘aspirin resist- ance’ [13]. Otherwise, an insufficient inhibition of throm- boxane formation is independently associated with an increased risk of cardiovascular events [14,15]. Apart from this, residual platelet cyclooxygenase-1 (COX-1) function measured by serum thromboxane B2 correlates with subsequent major adverse cardiovascular events [16]. Incomplete platelet inhibition by aspirin is especially common in patients with diseases such as diabetes [17], and essential thrombocytemia [18], as well as in patients receiving coronary artery bypass grafting (CABG) surgery [19]. To the best of our knowledge, the relationship between SUA levels and aspirin resistance in patients with CAD has not been evaluated, though investigators have ident- ified several factors that affect aspirin resistance. In the present study, we therefore investigated the association between SUA level and aspirin resistance in patients with CAD. Materials and methods Study design and population During March 2011 and January 2014, 245 consecutive patients (134 women; mean age 63.55  10.61 years) with stable angina pectoris (SAP) who underwent coronary angiography and documented more than 50% occlusion in a major coronary artery were recruited for this study. Each participant was randomly assigned to either the 412 Original article 0957-5235 Copyright ß 2016 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/MBC.0000000000000466