Cytokine activation and disease progression in patients with stable moderate chronic heart failure

Background: Activation of the cytokine and the complement system is associated with disease progression in severe congestive heart failure (CHF). Magnitude and prognostic relevance of cytokine and complement activation remain uncertain in patients with moderate CHF. Objectives: Measurement of cytokine and complement activation in patients with moderate CHF and testing whether C-reactive protein (CRP), can serve as a surrogate marker of their activation, adding independent prognostic information when co-measured with B-type natriuretic peptide (BNP). Methods: The 118 study participants were separated into three groups based on pre-determined CRP and BNP levels: Group I (n = 27; CRP >5 mg/liter, BNP >= 200 pg/ml); Group II (n = 46; CRP <= 5 mg/liter, BNP :200 pg/ml); and Group III (n = 45; CRP :5;5 mg/liter, BNP <200 pg/ml). Results: Mortality was high in Group I (30%; log-rank p < 0.001) but low in Groups II and III (2% and 4%, respectively; log rank, p = 0.7). No differences were observed for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) between Groups I and II (31 +/- 16 vs 32 +/- 14% and 66 +/- 16 vs 65 +/- 11 mm, respectively), whereas in Group III LVEF was higher (42 +/- 17%, p = 0.002) with smaller LVEDD (57 +/- 13 mm, p = 0.012). Cytokine sCD14 and tumor necrosis factor (TNF)-alpha levels were not different between the three groups. However, interleukin-6 levels (9.75 +/- 8.17 pg/ml,p = 0.001) and the terminal complement complex C5b-9 (109.9 +/- 68 ng/ml; p = 0.04) were elevated in Group I, both correlating with CRP (interleukin-6: r = 0.5, p < 0.001; C5b-9: r = 0.41, p = 0.001). Conclusions: CRP may be used as a surrogate parameter for interleukin-6 and complement activation in moderate CHF. CRP in combination with BNP identifies a high-risk group with a tendency for poor outcome not discriminated by cardiac function.