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Circulation. 2000;102:3060-3067

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(Circulation. 2000;102:3060.)
© 2000 American Heart Association, Inc.


Clinical Investigation and Reports

Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure

Mathias Rauchhaus, MD; Wolfram Doehner, MD; Darrel P. Francis, MD; Constantinos Davos, MD, PhD; Michael Kemp, FRCPath; Christa Liebenthal; Josef Niebauer, MD, PhD; James Hooper, MD; Hans-Dieter Volk, MD; Andrew J. S. Coats, DM; Stefan D. Anker, MD, PhD

From Clinical Cardiology, National Heart and Lung Institute (M.R., W.D., D.P.F., C.D., J.N., A.J.S.C., S.D.A.), and Biochemistry, Royal Brompton Hospital (M.K., J.H.), London, UK; the Universitätsklinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität (M.R.), Halle, Germany; and the Institut für Medizinische Immunologie, Charité (Campus Mitte) (C.L., H.-D.V.), and Franz-Volhard-Klinik (Charité, Campus Berlin-Buch) am Max-Delbrück Centrum für Molekulare Medizin (S.D.A.), Berlin, Germany.

Correspondence to Mathias Rauchhaus, MD, Universitätsklinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität, Ernst-Grube-Str. 40, 06097 Halle, Germany. E-mail mathias.rauchhaus{at}medizin.uni-halle.de

Background—Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-{alpha} (TNF-{alpha}), soluble TNF-receptor 1 and 2 (sTNF-R1/sTNF-R2), interleukin-6 (IL-6), and soluble CD14 receptors (sCD14) in CHF patients.

Methods and Results—In 152 CHF patients (age 61±1 years, New York Heart Association [NYHA] class 2.6±0.1, peak O2 17.3±0.6 mL · kg-1 · min-1, mean±SEM) plasma concentrations of immune variables were prospectively assessed. During a mean follow-up of 34 months (>12 months in all patients), 62 patients (41%) died. Cumulative mortality was 28% at 24 months. In univariate analyses, increased total and trimeric TNF-{alpha}, sTNF-R1, and sTNF-R2 (all P<=0.0001), sCD14 (P=0.0007), and IL-6 (P=0.005) predicted 24-month mortality. With multivariate analysis and receiver operating characteristics, sTNF-R1 emerged among all cytokine parameters as the strongest and most accurate prognosticator in this CHF population, regardless of follow-up duration and independently of NYHA class, peak O2, E/CO2 slope, left ventricular ejection fraction, and wasting (P<0.001). The receiver operating characteristic area under the curve for sTNF-R1 was greater than for sTNF-R2 at 6, 12, and 18 months (all P<0.05).

Conclusions—sTNF-R1 was the strongest and most accurate prognosticator, independent of established markers of CHF severity. Assessment of sTNF-R1 may be useful in identifying patients who are at high risk of death and in monitoring patients undergoing anti–TNF-{alpha} treatment.


Key Words: heart failure • immune system • proteins • prognosis • mortality




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