title: Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction.
abstract: OBJECTIVE
  Interleukin (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.
  
  
  RESULTS
  We used data from 981 patients enrolled in the prospective, multicentre French registry of Acute ST elevation, or non-ST-elevation Myocardial Infarction (Fast-MI, NCT00673036). Serum levels of IL-17 were associated with the risk of all-cause 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, C-reactive protein, 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 vascular cell adhesion molecule (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).
  
  
  CONCLUSIONS
  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 the IL-17 pathway in clinical settings associated with a high cardiovascular risk.
  
  
  BACKGROUND
  NCT00673036.
authors.affiliation: Department of Clinical Pharmacology, URC-EST, Assistance Publique-Hôpitaux de Paris (APHP), Hôpital St Antoine Paris, University of Pierre et Marie Curie, 27 Rue Chaligny, 75012 Paris, France. tabassome.simon@sat.aphp.fr
authors.forename: Tabassome
authors.initials: T
authors.lastname: Simon
authors.forename: Soraya
authors.initials: S
authors.lastname: Taleb
authors.forename: Nicolas
authors.initials: N
authors.lastname: Danchin
authors.forename: Ludivine
authors.initials: L
authors.lastname: Laurans
authors.forename: Benoit
authors.initials: B
authors.lastname: Rousseau
authors.forename: Simon
authors.initials: S
authors.lastname: Cattan
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Montely
authors.forename: Olivier
authors.initials: O
authors.lastname: Dubourg
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Salma
authors.initials: S
authors.lastname: Kotti
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D019010:Vascular Cell Adhesion Molecule-1