Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction Fabiola Olivieri a, c, ⁎, Roberto Antonicelli d , Maria Lorenzi c , Yuri D'Alessandra h , Raffaella Lazzarini c , Gabriele Santini b , Liana Spazzafumo f , Rosamaria Lisa d , Lucia La Sala a , Roberta Galeazzi e , Rina Recchioni c , Roberto Testa g , Giulio Pompilio h, i , Maurizio C. Capogrossi j , Antonio Domenico Procopio a, c a Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy b Department of Biomedical Sciences, Università Politecnica delle Marche, Ancona, Italy c Center of Clinical Pathology and Innovative Therapy, INRCA-IRCCS, Ancona, Italy d Coronary Care Unit — Ospedale “U. Sestilli”, INRCA-IRCCS, Ancona, Italy e Clinical Laboratory & Molecular Diagnostics, INRCA-IRCCS, Ancona, Italy f Statistical Center, INRCA-IRCCS, Ancona, Italy g Metabolic and Nutrition Research Center on Diabetes, INRCA-IRCCS, Ancona, Italy h Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico “Monzino”— IRCCS, Milano, Italy i Department of Cardiovascular Sciences, University of Milan, Italy j Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata — IRCCS, Roma, Italy abstract article info Article history: Received 27 July 2011 Received in revised form 13 December 2011 Accepted 22 January 2012 Available online xxxx Keywords: Circulating microRNAs Biomarkers Myocardial infarction Heart failure Aging Background: Geriatric patients with acute non-ST elevation myocardial infarction (NSTEMI) can frequently present atypical symptoms and non-diagnostic electrocardiogram. The detection of modest cardiac troponin T (cTnT) elevation is challenging for physicians needing to routinely triage these patients. Unfortunately, non-coronary diseases, such as acute heart failure (CHF), may cause cTnT elevation. Circulating microRNAs (miRs) have emerged as biomarkers of MI. However, their diagnostic potential needs to be determined in elderly NSTEMI patients. Methods: 92 NSTEMI patients (82.6 ± 6.9 years old; complicated by CHF in 74% of cases) and 81 patients with acute CHF without AMI (81.3 ± 6.8 years old) were enrolled at presentation. A third group comprised 99 age- matched healthy control subjects (CTR). Plasma levels of miR-1, -21, -133a, -208a, -423-5p and -499-5p were analyzed. Results: MiR-1, -21 -133a and -423-5p showed a 3- to 10-fold increase and miR-499-5p exhibited > 80-fold increase in acute NSTEMI patient vs. CTR. MiR-499-5p and -21 showed a significantly increased expression in NSTEMI vs. CHF. Interestingly, mir-499-5p was comparable to cTnT in discriminating NSTEMI vs. CTR and CHF patients. Its diagnostic accuracy was higher than conventional and hs-cTnT in differentiating NSTEMI (n = 31) vs. acute CHF (n = 32) patients with modest cTnT elevation at presentation (miR-499-5p AUC = 0.86 vs. cTnT AUC = 0.68 and vs. hs-cTnT AUC = 0.70). Conclusions: Circulating miR-499-5p is a sensitive biomarker of acute NSTEMI in the elderly, exhibiting a diagnostic accuracy superior to that of cTnT in patients with modest elevation at presentation. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The prevalence of acute coronary syndromes (ACS) increases with age [1]. In elderly patients, the incidence of myocardial infarction (MI) is high, with mortality rates exceeding 30% [2]. However, the recognition of acute myocardial infarction (AMI) in old individuals is often challenging, particularly in the presence of non-ST-elevation MI (NSTEMI) [3]. In geriatric patients the symptoms of NSTEMI may be atypical, the electrocardiogram (ECG) inconclusive because of a preexisting left bundle branch block, the presence of a cardiac pace- maker, and diffused ECG changes due to chronic ischemic cardiomy- opathy or previous MIs [3–5]. Further, the diagnostic value of cTnT, International Journal of Cardiology xxx (2012) xxx–xxx Abbreviations: AMI, acute myocardial infarction; AUC, area under the ROC curve; CHF, congestive heart failure; cTnT, cardiac troponin T; hs, high sensitivity; LVEF, left ventricular ejection fraction; MI, myocardial infarction; miRNA, microRNA; NSTEMI, non-ST elevation myocardial infarction; qRT-PCR, quantitative real time polymerase chain reaction; ROC, receiver operator characteristic; TTE, trans-thoracic 2D echocardi- ography; WMSI, wall motion score index. ⁎ Corresponding author at: Dept. Clinical and Molecular Sciences, Università Politec- nica delle Marche, Ancona, Via Tronto 10/A — 60020 Ancona (Italy). Tel.: + 39 071 2206242; fax: + 39 071 2206240. E-mail address: f.olivieri@univpm.it (F. Olivieri). IJCA-14440; No of Pages 6 0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.01.075 Contents lists available at SciVerse ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: Olivieri F, et al, Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myo- cardial infarction, Int J Cardiol (2012), doi:10.1016/j.ijcard.2012.01.075