Interleukin-6 and B-type natriuretic peptide are independent predictors for worsening of heart failure in patients with progressive congestive heart failure

Background: Neurohormones and cytokines have been associated with poor prognosis in patients with congestive heart failure. However, direct comparisons between them are rare and the best predictor for worsening of heart failure remains to be elucidated. The aim of the study was to identify independent predictors for worsening of heart failure. Methods: We studied 100 patients with congestive heart failure (LVEF less than or equal to25%). Serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, aminoterminal atrial natriuretic peptide (N-ANP), B-type natriuretic peptide (BNP), aminoterminal B-type natriuretic peptide (N-BNP), norepinephrine (NE) and big endothelin (big ET) were measured at entry into the study. Univariate and stepwise multivariate regression analyses were performed to compare variables and clinical parameters. The end-point was defined as worsening of heart failure. Results: During follow-up (mean 378 days), 30 patients reached the defined end-point. Univariate risk factors of worsening of heart failure were IL-6 (p = 0.0001), log BNP (p = 0.0001), log N-ANP (p = 0.0259), big ET (p = 0.0032), log N-BNP (p = 0.0495), NE (p = 0.0013) and LVEF (p = 0.0498). Multivariate regression analysis identified IL-6 as the strongest independent predictive value for worsening of heart failure (p = 0.0001), followed by log BNP (p = 0.0002). Mean IL-6 levels were 1.76 +/- 1.73 in stable patients and 4.62 +/- 7.98 pg/ml in patients who developed worsening of heart failure. Using a cut-off value of 1.66 pg/ml for IL-6 Kaplan-Meier freedom from worsening, heart failure was significantly higher in patients below this cut-off point compared with those above (P = 0.0002). Conclusions: IL-6 and BNP independently predict worsening of heart failure. A single measurement could help to identify patients at high risk for worsening of heart failure and these individuals should be monitored more closely.