Prognostic value of serum cytokines in patients with congestive heart failure

Background: Increased levels of circulating cytokines have been previously reported in patients with congestive heart failure; however, whether they h ave prognostic implications is still unknown. The aim of this study was to assess the prognostic implications of elevated serum cytokines in patients with heart failure and to identify the predictors of cytokine activation. Methods and Results: We assessed neurohormonal determinations, circulating cytokines, ejection fraction (EF) and end-diastolic and end-systolic left v entricular lengths in 87 patients (aged 57 +/- 9 years) with left ventricul ar dysfunction (EF 24% +/- 6%). In 48 patients, we also assessed cytokine r eceptors. During follow-up (mean, 14 +/- 9 months), 8 patients died and 12 had new heart failure episodes that required hospital admission, 5 of whom underwent heart transplantation. The univariate predictors of these events were serum interleukin-6 (IL-6) (p = 0.00001), New York Heart Association ( NYHA) functional class (p = 0.0004), tumor necrosis factor-soluble receptor I (p = 0.001), atrial natriuretic peptide (p = 0.002), tumor necrosis fact or-soluble receptor II (p = 0.004), angiotensin II (p = 0.006), serum inter leukin-1 beta (p = 0.01), and plasma renin activity (p = 0.02). Increased s erum interleukin-6 (>10 pg/ml) was a significant predictor of death or new heart failure episodes according to the Kaplan-Meier survival method by log -rank test (p = 0.004). By Cox regression analysis, serum IL-6 (p = 0.0005) and the NYHA functional class (p = 0.005) were identified as independent p redictors of prognosis. Conclusions: In patients with congestive heart failure, increased serum IL- 6 was identified as a powerful independent predictor of the combined end po int: death, new heart failure episodes, and need for heart transplantation.