(Circulation. 2000;102:3060.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure
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-
(TNF-), 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-,
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-
treatment.
Key Words: heart failure • immune system • proteins • prognosis • mortality
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