(Circulation. 2002;106:24.)
© 2002 American Heart Association, Inc.
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Clinical Investigation and Reports
Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina
Stefan Blankenberg, MD; Laurence Tiret, PhD; Christoph Bickel, MD; Dirk Peetz, MD; François Cambien, MD; Jürgen Meyer, MD; Hans J. Rupprecht, MD for the AtheroGene Investigators*
From the Department of Medicine II (S.B., C.B., J.M., H.J.R.) and the Department of Clinical Chemistry (D.P.), Johannes Gutenberg-University, Mainz, Germany; and INSERM U525, Faculté de Médecine Pitié-Salpétrière (S.B., L.T., F.C.), Paris, France.
Correspondence to Stefan Blankenberg, MD, INSERM U 525, Faculté de Médecine Pitié-Salpétrière, 91 bld de l’Hôpital, 75634 Paris cedex 13, France. E-mail stefan.blankenberg@chups.jussieu.fr
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.
Methods and 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. |
