Letter to the Editor Admission levels of circulating miR-499-5p and risk of death in elderly patients after acute non-ST elevation myocardial infarction Fabiola Olivieri a,b, ⁎, Roberto Antonicelli c , Liana Spazzafumo d , Gabriele Santini a , Maria Rita Rippo a , Roberta Galeazzi e , Simona Giovagnetti e , Yuri D'Alessandra f , Fiorella Marcheselli b , Maurizio C. Capogrossi g , Antonio Domenico Procopio a,b a Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy b Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA—IRCCS), Ancona, Italy c Department of Cardiology (CCU), “U. Sestili” Hospital, INRCA—IRCCS, Ancona, Italy d Biostatistical Center, INRCA—IRCCS, Ancona, Italy e Clinical Laboratory & Molecular Diagnostics, INRCA—IRCCS, Ancona, Italy f Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Centro Cardiologico “Monzino”, IRCCS, Milano, Italy g Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata (IDI), IRCCS, Roma, Italy article info Article history: Received 6 November 2013 Accepted 28 December 2013 Available online 8 January 2014 Keywords: MicroRNA Acute myocardial infarction Prognosis Elderly patients MiR-499-5p Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality in Western countries [1]. More than half of all acute cardiac events are classified as non-ST elevation myocardial infarction (NSTEMI). NSTEMI is a common condition in geriatric subjects. The prognosis for AMI is related to a combination of heart disease and risk factors for which several risk score models are available [2]. In contrast, despite extensive investigation, there is currently no biomarker or biomarker combination capable of accurately predicting outcomes based on AMI conditions at admission, especially in elderly/old patient [3]. The discovery of circulating microRNAs (miRNAs) has opened intriguing possibilities to use their expression patterns as diagnostic biomarkers for AMI [4]. However few studies have explored the prognostic value of circulating miRNAs in AMI patients [5,6]. We previously demonstrated in a sample of elderly NSTEMI patients that miR-499-5p was the circulating miRNA with the best diagnostic International Journal of Cardiology 172 (2014) e276–e278 ⁎ Corresponding author at: Dept. Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Via Tronto 10/A, 60020 Ancona, Italy. Tel.: +39 071 220 6242; fax: +39 071 220 6240. E-mail address: f.olivieri@univpm.it (F. Olivieri). performance [7]. In a concomitant study we reported that circulating miR-21 levels increase in NSTEMI patients and correlate significantly with the concentrations of conventional circulating inflammatory biomarkers, such as C-reactive protein (CRP) and fibrinogen [8]. To test the hypothesis that miR-499-5p and miR-21 can serve as prognostic biomarkers to identify subjects at high risk of post-NSTEMI cardiovascular death, we asked all NSTEMI patients presenting to the Coronary Care Unit of INRCA Hospital (Ancona, Italy) from January 2009 to January 2010 for their informed consent to participate in this study, whose protocol was approved by the local Ethics Committee. Only patients with an interval of 4–9 h from symptom onset to admission were included. Since percutaneous coronary angioplasty (PTCA) and/or coronary artery bypass grafting (CABG) are not a primary goal in old NSTEMI patients [9], patients receiving invasive procedures were excluded, to avoid any bias related to approach invasiveness vs. non-invasiveness. NSTEMI was diagnosed according to European Society of Cardiology (ESC) guidelines as described previously [7]. Overall, 155 patients were recruited. Since 5 patients dropped out and the samples of 8 patients were not correctly processed, 142 patients were eventually included in survival analysis. Cardiovascular mortality at 12 and 24 months was prospectively defined as the primary endpoint of the study. Overall, 1-year mortality was 38% and 2-year mortality was 45%. MiR-499-5p, miR-21, high-sensitivity (hs) CRP, total homocysteine (tHcy) and cardiac troponin T (cTnT) were quantified as described previously [7]. Patients' admission clinical and laboratory characteristics are reported in Table 1. Univariate analysis disclosed that age, hs-CRP, tHcy, white blood cell count and body mass index at admission were significantly different between the patients who died within the first 12 months and survivors. Moreover, the percentage of NSTEMI patients with congestive heart failure (CHF) and of those with Killip class 3 or 4 was significantly higher among those who died within a year, as expected. Interestingly, the proportion of NSTEMI patients whose admission miR-499-5p level exceeded the median was significantly higher among those who died within a year compared with survivors. The dif- ference of miR-21 levels was barely significant between the two groups. 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.203 Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard