Objectives. The object of the study was to assess the relationship between erythrocyte sedimentation rate (ESR) and inflammatory cytokine production in chronic heart failure (CHF). Our findings lead us to re-evaluate the prognostic value of the ESR in assessing patients with CHF. Background. The search for simple prognostic markers in CHF that can be assessed anywhere at low cost is important. Increases in ESR are related to the acute phase response in states of inflammation and infection. Methods. Initially, we studied ESR in relation to plasma levels of inflammatory cytokines in 58 CHF patients. The findings prompted us to analyze the mortality predictive power of ESR compared with established risk factors in these patients and (retrospectively) in a second group of 101 clinically stable CHF patients who had ESR measured. Results. In all 159 CHF patients (age 62 ± 2 years, New York Heart Association [NYHA] class 2.7 ± 0.1), ESR ranged from 1 to 96 mm/h (median 14 mm/h). The ESR was correlated with tumor necrosis factor (TNF)-alpha (r = 0.31, p < 0.05), soluble TNF receptor-1 (r = 0.48, p < 0.0005), soluble TNF receptor-2 (r = 0.39, p < 0.005) and interleukin 6 (r = 0.45, p < 0.005) levels. High ESR levels indicated a poor prognosis (p < 0.0001), and this was independent of age, NYHA class, ejection fraction and peak oxygen consumption (p < 0.005). Patients with ESR above median (≥15 mm/h) compared with patients with ESR <15 mm/h had an impaired survival (hazard ratio 2.62, 95% confidence interval 1.58-4.36, p < 0.0001). Conclusions. Our study demonstrates that in CHF a high ESR is an unfavorable prognostic sign, independent of patients' symptomatology and ventricular function. These results are in diametrical contrast to previous results. This may reflect a change in the underlying pathophysiology due to today's treatment with angiotensin-converting enzyme inhibitors. (C) 2000 by the American College of Cardiology.