Plasma urocortin in acute myocardial infarction patients Arintaya Phrommintikul *,† , Sivaporn Sivasinprasasn *,‡ , Narissara Lailerd *,‡ , Siriporn Chattipakorn *,§ , Srun Kuanprasert *,† and Nipon Chattipakorn *,†,‡,¶ * Cardiac Electrophysiology Research and Training Center, † Cardiology Division, Department of Internal Medicine, ‡ Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, § Department of Oral Biology and Diagnostic Science, Faculty of Dentistry and ¶ Biomedical Engineering Center, Chiang Mai University, Chiang Mai, Thailand ABSTRACT Background Despite its proposed cardioprotective effect, the role of plasma urocortin in acute myocardial infarction (AMI) remains unknown. We investigated plasma profile of urocortin in AMI patients and evaluated its long-term prognostic performance. Material and methods Sixty-six AMI patients and 21 healthy subjects were included in this study. Blood samples for urocortin were collected on days 0 (onset), 1, 3 and 5 and at 3 and 6 months. Primary endpoint was mortality within 1 year of follow-up. Secondary endpoint was combined death and nonfatal adverse cardiac events (i.e. myocardial reinfarction, urgent revascularization or hospitalization due to heart failure) within 1 year. Results During follow-up at 1 year, 38 (57Æ6%) patients were alive without cardiac events, nine (13Æ6%) had nonfatal cardiac events and 17 (25Æ8%) died. Plasma urocortin in AMI patients were increased on days 0, 1, 3 and 5 (P <0Æ05 vs. control). The receiver-operating characteristic curve showed an area under curve (AUC) of day 0 urocortin to be 0Æ750 with 95% confidence interval (CI) of 0Æ619–0Æ881 (P =0Æ004), whereas AUC of NT- proBNP was 0Æ857 (95% CI, 0Æ722–0Æ992; P =0Æ003). Sensitivity values for predicting the mortality of urocortin NT-proBNP and a combined urocortin and NT-proBNP were 0Æ81 (95% CI, 0Æ54–0Æ95), 0Æ86 (95% CI, 0Æ42–0Æ99) and 1Æ0 (95% CI, 0Æ56–1Æ0), respectively. Conclusions Plasma urocortin level is elevated in AMI patients for 5 days from onset. High plasma urocortin within 24 h after the onset is associated with increased mortality. Combined urocortin and NT-proBNP enhance prognostic performance in AMI patients. Keywords Acute myocardial infarction, cardiac function, cardiac markers, urocortin. Eur J Clin Invest 2010; 40 (10): 874–882 Introduction Biochemical markers play a pivotal role in the diagnosis and management of patients with acute coronary syndromes [1–3]. The multi-marker approach for prognostic and risk stratifica- tion has been indicated for its benefits in predicting the future adverse cardiac events in these patients [4]. In the past decades, advanced techniques in biomarker investigation have led inves- tigators to the discovery of several novel bioactive peptides that could be potentially useful in prognostic evaluation. Urocortin is a peptide belonging to the corticotrophin-releas- ing factor peptide family. Urocortin is released when the heart is under stress (such as ischaemia or heart failure) and has been demonstrated in both animal and human studies [5,6]. It has been shown to cause coronary vasodilatation, positive inotropic effect, and also has an anti-apoptotic effect in the myocardium that has undergone ischaemia–reperfusion injury [7]. In clinical situations, urocortin levels have been shown to elevate in patients with systolic heart failure (left ventricular ejection frac- tion, LVEF, £ 45%), especially in the New York Heart Associa- tion (NYHA) functional classes I–II [5]. Growing evidence suggests that urocortin may have cardio- protective effects and could play an important role in both nor- mal and diseased hearts [8–11]. In experimental sheep models, urocortin has profound and sustained haemodynamic, hor- monal and renal effects, and its level was increased in sheep with systolic heart failure [5,11]. During ischaemia ⁄ reperfusion, the cardioprotective effects of urocortin were reflected in increased cell survival [12], reduced infarct size [13,14], improved contractile function [15], reduced arrhythmic 874 European Journal of Clinical Investigation Vol 40 DOI: 10.1111/j.1365-2362.2010.02343.x ORIGINAL ARTICLE