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Cited by 810Heart Failure Treatment and ManagementCardiac Fibrosis and RemodelingInflammatory Biomarkers in Disease Prognosis

Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure

Rauchhaus, Mathias, Doehner, Wolfram, Francis, Darrel P., Davos, Constantinos, Kemp, Michael, Liebenthal, Christa, Niebauer, Josef, Hooper, James +3 more·2000·Circulation
DOI 10.1161/01.cir.102.25.3060
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Abstract

Background —Inflammatory immune activation is an important feature in chronic heart failure (CHF). Little is known about the prognostic importance of tumor necrosis factor-α (TNF-α), 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 V̇ o 2 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-α, 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 V̇ o 2 , V̇ e /V̇ co 2 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-α treatment.

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Crossref · 10.1161/01.cir.102.25.3060

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  • Patients with heart failure have alterations in intestinal integrity, and elevated levels of pro-inflammatory cytokines in the blood correlate with symptom severity and poorer outcomes.

    “Multiple studies show patients with heart failure have alterations in intestinal integrity, and that elevated levels of pro-inflammatory cytokines in the blood correlate with symptom severity and poorer outcomes20, 21.”

    From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [21]

  • In heart failure subjects, heightened circulating levels of multiple cytokines (TNF, IL-1, and IL-6) are associated with more severe clinical symptoms and can predict poorer patient survival.

    “In heart failure subjects, heightened circulating levels of multiple cytokines (e.g., TNF, IL-1, and IL-6) are associated with more severe clinical symptoms and can predict poorer patient survival43–45.”

    From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [44]

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Authors
Rauchhaus, M., Doehner, W., Francis, D. P., Davos, C., Kemp, M., Liebenthal, C., Niebauer, J., Hooper, J., Volk, H.-D., Coats, A. J. S., & Anker, S. D.
Affiliations
  • Royal Brompton Hospital (GB)
  • 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.),...
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2000-12-19
Volume
102
Issue
25
Pages
3060-3067
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.102.25.3060
OpenAlex
W2066885413
Cited by
810
References
27
Citations by year
2026: 15 · 2025: 19 · 2024: 25 · 2023: 20 · 2022: 31 · 2021: 24 · 2020: 31 · 2019: 22 · 2018: 26 · 2017: 24 · 2016: 24 · 2015: 24 · 2014: 35 · 2013: 35 · 2012: 35
FWCI
21.26
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
Keywords
chronic heart failure, plasma cytokines, soluble TNF receptor 1, soluble TNF receptor 2, TNF-α, interleukin-6, soluble CD14, inflammation, mortality prediction, prognostic factors, anti-TNF therapy
MeSH terms
Adult, Aged, Aged, 80 and over, Analysis of Variance, Cardiac Output, Low, Chronic Disease, Female, Humans, Immunoassay, Male, Middle Aged, Prognosis, ROC Curve, Solubility, Tumor Necrosis Factor-alpha, Biomarkers, Antigens, CD, Interleukin-6, Survival Analysis, Cytokines, Receptors, Tumor Necrosis Factor, Lipopolysaccharide Receptors, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II

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