Cited by 2,582Heart Failure Treatment and ManagementCardiac Fibrosis and RemodelingNutrition and Health in Aging

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Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

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Levine, Beth, Kalman, Jill, Mayer, Lloyd, Fillit, Howard M., Packer, Milton·1990·New England Journal of Medicine

DOI 10.1056/nejm199007263230405

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Abstract

BACKGROUND AND METHODS: Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS: Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS: These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.

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Serum HER2 Levels are Increased in Patients with Chronic Heart Failure
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“Elevated plasma levels of TNF-a have been reported in a variety of cardiovascular diseases, including acute myocarditis (35), cardiac allograft rejection (8), myocardial infarction (36), and congestive heart failure (32, 34), as well as in endotoxemia (17, 51, 54).”
Background
Tumour necrosis factor is expressed in cardiac tissues of patients with heart failure
Doyama, K., Fujiwara, H., Fukumoto, M., Tanaka, M., Fujiwara, Y., Oda, T., Inada, T., Ohtani, S., Hasegawa, K., Fujiwara, T., et al. (1996) · International Journal of Cardiology · doi:10.1016/0167-5273(96)02607-1 · Cited by 54
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Functional improvement in heart failure patients treated with beta-blockers is associated with a decline of cytokine levels
Mayer, B., Holmer, S. R., Hengstenberg, C., Lieb, W., Pfeifer, M. A., & Schunkert, H. (2005) · International Journal of Cardiology · doi:10.1016/j.ijcard.2004.08.053 · Cited by 51
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Activation of p38 Mitogen-Activated Protein Kinase Contributes to the Early Cardiodepressant Action of Tumor Necrosis Factor
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REACTIVE OXYGEN SPECIES INDUCE CARDIOMYOCYTE APOPTOSIS PARTLY THROUGH TNF-α
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Background
Vasodilatory effects of C-type natriuretic peptide on forearm resistance vessels are distinct from those of atrial natriuretic peptide in chronic heart failure.
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Authors: Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M.
Affiliations: City University of New York (US)
ORCID: Levine, Beth
Fillit, Howard M.
Packer, Milton
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1990-07-26
Volume: 323
Issue: 4
Pages: 236-241
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199007263230405
OpenAlex: W2324476825
Cited by: 2,582
References: 55
Citations by year: 2026: 21 · 2025: 43 · 2024: 49 · 2023: 34 · 2022: 70 · 2021: 63 · 2020: 64 · 2019: 64 · 2018: 59 · 2017: 64 · 2016: 58 · 2015: 70 · 2014: 75 · 2013: 73 · 2012: 79
FWCI: 29.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (7r01hl025055-11, 5r01ca041583-06, 5k04hl001229-02)
National Heart, Lung, and Blood Institute (KO4-HL-01229, R01-HL-25055)
National Cancer Institute (R01-CA41583)
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 › Physiology (medical) › Nutrition and Health in Aging
Keywords: TNF-α, chronic heart failure, cardiac cachexia, serum cytokines, plasma renin activity, serum sodium, hemoglobin, blood urea nitrogen, chronic kidney disease, cytokine clearance, advanced heart failure, weight loss, inflammation in heart failure, anemia of heart failure, hyperuricemia, hyperkalemia
MeSH terms: Adult, Aged, Aged, 80 and over, Chronic Disease, Female, Heart Failure, Hemoglobins, Humans, Male, Middle Aged, Renin, Sodium, Tumor Necrosis Factor-alpha

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Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure

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