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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
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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V.M. Conraads, P. Beckers, J. Bosmans, L.S. De Clerck, W.J. Stevens, C.J. Vrints, and D.L. Brutsaert Combined endurance/resistance training reduces plasma TNF-{alpha} receptor levels in patients with chronic heart failure and coronary artery disease Eur. Heart J., December 1, 2002; 23(23): 1854 - 1860. [Abstract] [Full Text] [PDF]
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P. J. Pugh, R. D. Jones, T.H. Jones, and K. S. Channer Heart failure as an inflammatory condition: potential role for androgens as immune modulators Eur J Heart Fail, December 1, 2002; 4(6): 673 - 680. [Abstract] [Full Text] [PDF]
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 J. R. R. Heyen, E. R. Blasi, K. Nikula, R. Rocha, H. A. Daust, G. Frierdich, J. F. Van Vleet, P. De Ciechi, E. G. McMahon, and A. E. Rudolph Structural, functional, and molecular characterization of the SHHF model of heart failure Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1775 - H1784. [Abstract] [Full Text] [PDF]
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S. Zeuke, A. J Ulmer, S. Kusumoto, H. A Katus, and H. Heine TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS Cardiovasc Res, October 1, 2002; 56(1): 126 - 134. [Abstract] [Full Text] [PDF]
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G. Vescovo, B. Ravara, A. Angelini, M. Sandri, U. Carraro, C. Ceconi, and L. D. Libera Effect of thalidomide on the skeletal muscle in experimental heart failure Eur J Heart Fail, August 1, 2002; 4(4): 455 - 460. [Abstract] [Full Text] [PDF]
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W. Schillinger, H. Schneider, K. Minami, R. Ferrari, and G. Hasenfuss Importance of sympathetic activation for the expression of Na+-Ca2+ exchanger in end-stage failing human myocardium Eur. Heart J., July 2, 2002; 23(14): 1118 - 1124. [Abstract] [Full Text] [PDF]
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P. R. Kalra, C. Anagnostopoulos, A. P. Bolger, A. J. S. Coats, and S. D. Anker The regulation and measurement of plasma volume in heart failure J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1901 - 1908. [Abstract] [Full Text] [PDF]
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T. B. Horwich, G. C. Fonarow, M. A. Hamilton, W. R. MacLellan, and J. Borenstein Anemia is associated with worse symptoms, greater impairment in functional capacity and a significant increase in mortality in patients with advanced heart failure J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1780 - 1786. [Abstract] [Full Text] [PDF]
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H. Krum and J. J. McMurray Statins and chronic heart failure: do we need a large-scale outcome trial? J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1567 - 1573. [Abstract] [Full Text] [PDF]
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R Sharma and S.D Anker From tissue wasting to cachexia: changes in peripheral blood flow and skeletal musculature Eur. Heart J. Suppl., April 1, 2002; 4(suppl_D): D12 - D17. [Abstract] [PDF]
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W. S. Bradham, B. Bozkurt, H. Gunasinghe, D. Mann, and F. G. Spinale Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective Cardiovasc Res, March 1, 2002; 53(4): 822 - 830. [Abstract] [Full Text] [PDF]
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R. Kell, A. Haunstetter, T.J. Dengler, C. Zugck, W. Kubler, and M. Haass Do cytokines enable risk stratification to be improved in NYHA functional class III patients?. Comparison with other potential predictors of prognosis Eur. Heart J., January 1, 2002; 23(1): 70 - 78. [Abstract] [Full Text] [PDF]
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A. P. Bolger, R. Sharma, P. Aukrust, L. Gullestad, H. Aass, J. G. Fjeld, L. Wikeby, A. K. Andreassen, H. Ihlen, S. Simonsen, et al. Increase in Anti-Inflammatory Cytokine Levels in Chronic Heart Failure: A Measure of Treatment Success or Failure? Response Circulation, October 30, 2001; 104 (18): e97 - e97. [Full Text] [PDF]
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 G. Zoppini, G. Faccini, M. Muggeo, L. Zenari, G. Falezza, and G. Targher Elevated Plasma Levels of Soluble Receptors of TNF-{alpha} and Their Association with Smoking and Microvascular Complications in Young Adults with Type 1 Diabetes J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3805 - 3808. [Abstract] [Full Text] [PDF]
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A. Deswal, N. J. Petersen, A. M. Feldman, J. B. Young, B. G. White, and D. L. Mann Cytokines and Cytokine Receptors in Advanced Heart Failure : An Analysis of the Cytokine Database from the Vesnarinone Trial (VEST) Circulation, April 24, 2001; 103(16): 2055 - 2059. [Abstract] [Full Text] [PDF]
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W. W. Parmley How Many Medicines Do Patients With Heart Failure Need? Circulation, March 27, 2001; 103(12): 1611 - 1612. [Full Text] [PDF]
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