Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina

作者：Stefan Blankenberg, Laurence Tiret, Christoph Bickel, Dirk Peetz, François Cambien, Jürgen Meyer, Hans J. Rupprecht · 发表于：Circulation · 年份：2002 · DOI：10.1161/01.cir.0000020546.30940.92 · 被引用次数：574 · 研究领域：Inflammasome and immune disorders、Atherosclerosis and Cardiovascular Diseases、Streptococcal Infections and Treatments

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 cardiovas...