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Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure
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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“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]
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“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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Metadata
- 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
- Published
- 2000-12-19
- Volume
- 102
- Issue
- 25
- Pages
- 3060-3067
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- 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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