Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: A report from the studies of left ventricular dysfunction (SOLVD)
Open accessAbstract
Objectives This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization.Background Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha. It is also unclear what the mechanism for the increased expression of proinflammatory cytokines is.Methods Tumor necrosis factor-alpha and interleukin-6 levels were analyzed by enzymes-linked immunoassay using randomly selected plasma samples from patients in functional classes I to III who were enrolled in neurohormonal substudies of the SOLVD trial; age-matched healthy subjects served as the control group.Results Plasma levels of tumor necrosis factor-alpha (p < 0.001) were elevated in patients in functional classes I to III ([mean +/- SD] 1.95 +/- 0.54, 2.63 +/- 0.48, 6.4 +/- 1.9 pg/ml, respectively) compared with age-matched control subjects (0.75 +/- 0.05 pg/ml) and were progressively elevated in relation to decreasing functional status of the patient. Plasma levels of interleukin-6 (p < 0.001) were elevated in patients in functional classes I to III (3.3 +/- 0.55, 6.2 +/- 1.1, 5.22 +/- 0.9 pg/ml, respectively) compared with age-matched control subjects (1.8 +/- 0.5 pg/ml and were progressively elevated in relation to decreasing functional status of the patient. Cox proportional-hazards analysis showed that there was a trend toward significance between plasma tumor necrosis factor-alpha (p < 0.07) and survival, whereas there was no significant relation for plasma interleukin-6 (p < 0.72). Except for atrial natriuretic factor, which correlated weakly (r = 0.23, p = 0.04) with circulating tumor necrosis factor-alpha levels, there was no significance correlation between neurohormonal and proinflammatory cytokine levels.Conclusions Circulating levels of proinflammatory cytokines increase in patients as their functional heart failure classification deteriorates. Moreover, activation of the neurohumoral axis is unlikely to completely explain the elaboration of proinflammatory cytokines in heart failure.
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In congestive heart failure, pro-inflammatory cytokines TNF, IL-6, and IL-1 are markedly elevated, and TNF level is a negative prognostic factor.
“in patients with congestive heart failure, the levels of pro-inflammatory cytokines, especially TNF, IL-6, and IL-1, are markedly elevated, and the TNF level is a negative prognostic factor”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [192]
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Self-citation
- Authors
- Torre-Amione, G., Kapadia, S., Benedict, C., Oral, H., Young, J. B., & Mann, D. L.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Mann, Douglas L.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 1996-04
- Volume
- 27
- Issue
- 5
- Pages
- 1201-1206
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1984235771
- Cited by
- 1,211
- References
- 22
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 16 · 2023: 17 · 2022: 36 · 2021: 34 · 2020: 30 · 2019: 27 · 2018: 23 · 2017: 41 · 2016: 34 · 2015: 28 · 2014: 34 · 2013: 42 · 2012: 43
- FWCI
- 26.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P50 HL_O6H)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- inflammatory cytokines, TNF-α, interleukin-6, heart failure, left ventricular dysfunction, NYHA functional class, atrial natriuretic peptide, survival, SOLVD trial, plasma cytokines, inflammation in heart failure, atrial fibrillation, atrial remodeling, neurohormonal activation, brain natriuretic peptide, angiotensin II, aldosterone, renin
- MeSH terms
- Aged, Enzyme-Linked Immunosorbent Assay, Female, Heart Failure, Humans, Male, Middle Aged, Tumor Necrosis Factor-alpha, Interleukin-6, Up-Regulation, Ventricular Dysfunction, Left
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