Severity of stable coronary artery disease and its biomarkers differ between men and women undergoing angiography Crystel M. Gijsberts a, b , Aisha Gohar a , Guilielmus H.J.M. Ellenbroek a , Imo E. Hoefer a , Dominique P.V. de Kleijn a, b, f, g , Folkert W. Asselbergs c, d, e , Hendrik M. Nathoe c , Pierfrancesco Agostoni c , Saskia Z.H. Rittersma c , Gerard Pasterkamp a , Yolande Appelman h , Hester M. den Ruijter a, * a Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Centre Utrecht, The Netherlands b ICIN-Netherlands Heart Institute, Utrecht, The Netherlands c Department of Cardiology, Division Heart and Lungs, University Medical Centre Utrecht, The Netherlands d Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands e Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom f Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore g Cardiovascular Research Institute, National University Heart Centre, National University Health System, Singapore h Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands article info Article history: Received 20 November 2014 Received in revised form 21 January 2015 Accepted 3 February 2015 Available online xxx Keywords: Epidemiology Sex Biomarkers Coronary angiography abstract Background: Coronary artery disease (CAD) affects both men and women. Cardiovascular biomarkers have been suggested to relate to CAD severity, but data on sex-specificity is scarce. Therefore, we investigated the association of established biomarkers with the severity of CAD in stable patients un- dergoing coronary angiography in a sex-specific manner. Methods: We studied stable patients undergoing coronary angiography and measured CAD severity by SYNTAX score and biomarker levels (N-terminal pro-brain natriuretic peptide (NT pro-BNP), high- sensitivity CRP (hsCRP), cystatin C (CysC), myeloperoxidase (MPO), high-sensitivity troponin I (hsTnI) and von Willebrand factor (VWF)). We tested for sex differences in SYNergy between percutaneous coronary intervention with TAXUS™ and cardiac surgery (SYNTAX) scores and biomarker levels using multivari- able ANCOVA. We investigated the association of biomarker levels with SYNTAX score in a multivariable linear regression with interaction terms for sex. Results: We analysed data on 460 men and 175 women. SYNTAX scores were significantly lower in women (9.99 points vs.11.88 points). Univariably, hsCRP and hsTnI levels were significantly associated with SYNTAX scores (both b 2.5). In multivariable analysis only hsCRP associated with SYNTAX score (b 1.9, p ¼ 0.009). Sex did not modify the association of biomarkers with SYNTAX score. Conclusion: CAD severity as quantified by SYNTAX score is lower in women than men based on coronary angiography. The association of biomarkers with CAD severity did not differ between the sexes. © 2015 Published by Elsevier Ireland Ltd. 1. Introduction CAD is the leading cause of mortality in both men and women worldwide [1]. Morbidity and death are attributed to the growth, destabilization or rupture of atherosclerotic plaques. Several mechanisms are implicated in the complex process of atherosclerosis; of most importance are inflammation [2], endo- thelial dysfunction and myocardial ischemia. Several biomarkers relating to these processes have been studied and implemented as non-invasive tools for the diagnosis of CAD and for the prediction of future cardiovascular events in primary prevention. Established biomarkers include: NT pro-BNP, which is associated with ven- tricular dilatation and pressure overload [3e5]; hsCRP [6,7], involved in the inflammatory process; CysC [8e11], a marker of renal dysfunction; MPO, linked to both inflammation and oxidative stress [12e14]; hsTnI [15e17], associated with myocardial ischemia * Corresponding author. Laboratory of Experimental Cardiology, University Medical Center, Heidelberglaan 100, 3508 GA, Utrecht, The Netherlands. E-mail address: H.M.denRuijter-2@umcutrecht.nl (H.M. den Ruijter). Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.002 0021-9150/© 2015 Published by Elsevier Ireland Ltd. Atherosclerosis xxx (2015) 1e7 Please cite this article in press as: C.M. Gijsberts, et al., Severity of stable coronary artery disease and its biomarkers differ between men and women undergoing angiography, Atherosclerosis (2015), http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.002