Independent and additive predictive value of total cholesterol content of erythrocyte membranes with regard to coronary artery disease clinical presentation Dimitrios N. Tziakas a, ⁎, Georgios K. Chalikias a , Dimitrios Stakos a , Ioannis K. Tentes b , Dimitrios Papazoglou c , Adina Thomaidi a , Anastasia Grapsa d , Georgia Gioka d , Juan Carlos Kaski e , Harisios Boudoulas f a University Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece b Biochemistry Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece c Internal Medicine Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece d Biochemistry Department, University Hospital of Alexandroupolis, Greece e Cardiovascular Biology Research Centre, St George's Hospital, University of London, London, UK f Center for Clinical Research, Foundation of Biomedical Research, Academy of Athens, Athens, Greece abstract article info Article history: Received 27 April 2009 Received in revised form 8 February 2010 Accepted 14 February 2010 Available online 12 March 2010 Keywords: Erythrocyte membranes Multiple biomarkers Cholesterol content Coronary artery disease Background: A new mechanism for clinical instability in coronary artery disease (CAD) has been proposed where erythrocytes could play an active role in atherosclerotic plaque growth and rupture. Clinical studies showed increased total cholesterol levels in the membrane of circulating erythrocytes (CEM) in acute coronary syndrome (ACS) patients compared to patients with chronic stable angina (CSA). We investigated the independent and incremental discriminating value of CEM along with N-terminal propeptide of BNP (NT-proBNP), high sensitivity C-reactive protein (hs CRP), myeloperoxidase (MPO) and apolipoprotein B (apoB) with regard to CAD clinical presentation. Methods: 519 consecutive angina patients were assessed; 252 had CSA (195 men, 62 ± 9 years) and 267 had ACS (213 men, 62 ± 10 years).CEM levels and serum concentrations of NT-proBNP, hs CRP, MPO and apoB were measured upon study admission. Results: Simple logistic regression models showed that all biomarkers could distinguish ACS, nevertheless CEM with greater potency (OR 9.26 95%CI 6.31–13.59, p b 0.001). Multiple logistic regression models after adjustment for all the variables that were different between the 2 groups as well as for other biomarkers showed that CEM continued to be a significant and an independent predictor of ACS (OR 22.27 95%CI 10.63–46.67, p b 0.001). An increment of the C-statistic was also shown when CEM levels were incorporated in the predictive model (including traditional vascular risk factors and new well established biomarkers i.e. hs CRP, MPO, apoB and NT-proBNP). Conclusions: The present study showed that CEM levels are associated with clinical instability in CAD patients in an independent and incremental manner. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction A new mechanism for clinical instability in coronary artery disease (CAD) has been proposed where erythrocytes could play an active role in atherosclerotic plaque growth and rupture leading to acute coronary syndromes (ACS) [1,2]. Histopathology studies showed that the necrotic lipid core of advanced atherosclerotic plaques contains erythrocyte membranes [3,4] and clinical studies showed increased total cholesterol levels in the membrane of circulating erythrocytes (CEM) in ACS patients compared to patients with chronic stable angina (CSA) [5]. Therefore, CEM has emerged among other non-traditional circulating biomarkers as a potential marker of CAD activity. However, in order to assess the value of a novel biomarker like CEM regarding its distinctive ability between clinical quiescence (CSA) and instability (ACS) in CAD, except from demonstrating increased levels among ACS patients, it should also be demonstrated that this novel biomarker improves the discriminating ability of an available model that incorporates several known markers that are increased in acute ischemic cardiac events [6]. Proof has been established with evidence for higher levels of various biomarkers in CAD instability (ACS) that may reflect diverse pathobio- logical substrates to the onset and complications of an acute ischemic syndrome such as B-type natriuretic peptide (BNP) —hemodynamic stress [7], high-sensitivity C-reactive protein (hs CRP) — inflammation [8], myeloperoxidase (MPO) — plaque rupture [9], and apolipoprotein-B (apoB) — lipid burden[10]. Therefore, we investigated the independent and incremental discriminating value of CEM along with N-terminal propeptide of International Journal of Cardiology 150 (2011) 22–27 ⁎ Corresponding author. Voulgaroktonou 23, 68100 Alexandroupolis, Greece. Tel.: +30 25510 35596 (home), +30 25510 76205 (office); fax: +30 25510 76245. E-mail address: dtziakas@med.duth.gr (D.N. Tziakas). 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.02.022 Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard