Circulating levels of interleukin-17 and cardiovascular outcomes in patients with acute myocardial infarction

Eur Heart J. 2013 Feb;34(8):570-7. doi: 10.1093/eurheartj/ehs263. Epub 2012 Sep 6.

Abstract

Aim: 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.

Methods and 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.

Clinical trials registration: NCT00673036.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Interleukin-17 / blood*
  • Interleukin-17 / physiology
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / mortality
  • Prognosis
  • Prospective Studies
  • Recurrence
  • Registries
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Interleukin-17
  • Vascular Cell Adhesion Molecule-1

Associated data

  • ClinicalTrials.gov/NCT00673036