title: Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina.
abstract: BACKGROUND
  Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking.
  
  
  RESULTS
  In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P<0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend <0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory variables IL-6, high-sensitive C-reactive protein, and fibrinogen, this relation remained almost unchanged, such that patients within the highest quartile of IL-18 had a 3.3-fold increase in hazard risk compared with those in the first quartile (95% CI, 1.3 to 8.4, P=0.01). This relation was observed in patients with stable angina and patients with unstable angina at baseline.
  
  
  CONCLUSIONS
  Serum IL-18 level was identified as a strong independent predictor of death from cardiovascular causes in patients with coronary artery disease regardless of the clinical status at admission. This result strongly supports recent experimental evidence of IL-18-mediated inflammation leading to acceleration and vulnerability of atherosclerotic plaques.
authors.affiliation: Department of Medicine II, Johannes Gutenberg-University, Mainz, Germany. stefan.blankenberg@chups.jussieu.fr
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.forename: Laurence
authors.initials: L
authors.lastname: Tiret
authors.forename: Christoph
authors.initials: C
authors.lastname: Bickel
authors.forename: Dirk
authors.initials: D
authors.lastname: Peetz
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Jürgen
authors.initials: J
authors.lastname: Meyer
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Rupprecht
mesh_terms: D000787:Angina Pectoris / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D000789:Angina, Unstable / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D020382:Interleukin-18