Oc026—Impact Of Circulating Levels Of Interleukin-17 And Cardiovascular Outcomes In Patients With Acute Myocardial Infarction

2013 e11 OC026—IMPACT OF CIRCULATING LEVELS OF INTERLEUKIN-17 AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION T. Simon; S. Taleb; N. Danchin; L. Laurans; B. Rousseau; S. Simon Cattan; J.-M. Montely; O. Dubourg; A. Tedgui; S. Kotti; and Z. Mallat Clinical Pharmacology, APHP, St Antoine Hospital, UPMCParis06, Paris; inserm; Cardiology, HEGP, APHP, Universite Paris Descartes, Paris; Inserm, U970; Clinical Pharmacology, URC-EST, APHP, Hopital St Antoine, UPMC-Paris 06 University, Paris; Cardiology, Montfermeil Hospital, Montfermeil; Cardiology, Aulnay Hospital, Aulnay; Cardiology, APHP, Ambroise Pare, Boulogne Billancourt; Clinical Pharmacology, URC-EST, APHP, Hopital St Antoine, Paris, France; and Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom Introduction and Background: IL-17 pathway is being clinically targeted in immune-mediated diseases, most of which are associated with a significant cardiovascular risk. We investigated the relationship between serum levels of IL-17 and the risk of cardiovascular events in patients with acute myocardial infarction. Patients (or Materials) and Methods: We used data from patients enrolled in the prospective, multicenter French registry of acute ST elevation or non–ST-elevation myocardial Infarction (Fast-MI, NCT00673036). Of the 374 centers in France that treated patients with acute MI, 223 (60%) participated in the registry. Among these, 100 centers recruited 1029 patients who contributed to a serum bank. Their baseline characteristics were comparable to the overall population of the registry. Written informed consent was provided by each patient. More than 99% of patients were Caucasian. Two-year follow-up was > 98% complete. Results: Serum levels of IL-17 were associated with the risk of allcause death and recurrent MI at 2 years, with levels of IL-17 below the median indicative of a worse outcome. The impact of IL-17 remained significant after adjustment for known cardiovascular risk factors, CRP, and treatments including statins: hazard ratio (HR) = 1.40 (1.03–1.91); P = 0.03.IL-17 inhibited mononuclear cell adhesion to endothelium and reduced endothelial VCAM-1 expression. Patients with low (below the median) IL-17 levels and high (above the median) soluble VCAM-1 (sVCAM-1) levels were at particularly increased risk of death and MI: adjusted HR = 2.22 (1.32–3.75) compared with the high IL-17/low sVCAM-1 group (P = 0.002). Conclusion: Low serum levels of IL-17 are associated with a higher risk of major cardiovascular events in Caucasian patients with acute MI. Our results raise possible concern about the use of inhibitors of IL-17 pathway in clinical settings associated with a high cardiovascular risk. Disclosure of Interest: T. Simon Other: Fast-MI is a registry if the French Society of Cardiology, supported by unrestricted grants from Pfizer and Servier and a research grant from the French Caisse Nationale d’Assurance Maladie. S. Taleb: None declared. N. Danchin: None declared. L. Laurans: None declared. B. Rousseau: None declared. S. Simon Cattan: None declared. J.-M. Montely: None declared. O. Dubourg: None declared. A. Tedgui: None declared. S. Kotti: None declared. Z. Mallat: None declared.