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CLINICAL STUDIES

The relationship of the erythrocyte sedimentation rate to inflammatory cytokines and survival in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors

Rakesh Sharma, BSc, MRCP^*, Mathias Rauchhaus, MD^* , Piotr P. Ponikowski, MD, PhD^*, Susan Varney, BSc^*, Philip A. Poole-Wilson, MD, FACC^*, Douglas L. Mann, MD, FACC, Andrew J. S. Coats, DM, FACC^* and Stefan D. Anker, MD, PhD^*

^* Department of Cardiac Medicine, National Heart & Lung Institute, Imperial College School of Medicine, London, United Kingdom
Department of Medicine, Veterans Administration Medical Center, Baylor College of Medicine, Houston, Texas, USA
Franz-Volhard-Klinik (Charité, Campus Berlin-Buch) at Max-Delbrück-Centrum for Molecular Medicine, Berlin, Germany
Department of Internal Medicine III, Martin-Luther University, Halle, Germany

Manuscript received October 20, 1999; revised manuscript received February 1, 2000, accepted March 30, 2000.

Reprint requests and correspondence: Dr. Stefan Anker, Cardiac Medicine, NHLI London, Dovehouse Street, London SW3 6LY, United Kingdom
s.anker{at}ic.ac.uk

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.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CHF = chronic heart failure   CI = confidence interval   ESR = erythrocyte sedimentation rate   IL-6 = interleukin 6   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   RR = hazard ratio   sTNFR = soluble tumor necrosis factor receptor   TNF = tumor necrosis factor   VO2 = oxygen consumption

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