Elevation of Tumor Necrosis Factor-α and Increased Risk of Recurrent Coronary Events After Myocardial Infarction
Abstract
Background —Levels of tumor necrosis factor-α (TNF-α) increase with acute ischemia. However, whether elevations of TNF-α in the stable phase after myocardial ischemia (MI) are associated with increased risk of recurrent coronary events is unknown. Methods and Results —A nested case-control design was used to compare TNF-α levels obtained an average of 8.9 months after initial MI among 272 participants in the Cholesterol And Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal cardiovascular event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (controls). Overall, TNF-α levels were significantly higher among cases than controls (2.84 versus 2.57 pg/mL, P =0.02). The excess risk of recurrent coronary events after MI was predominantly seen among those with the highest levels of TNF-α, such that those with levels in excess of 4.17 pg/mL (the 95th percentile of the control distribution) had an ≈3-fold increase in risk (RR=2.7, 95% CI 1.4 to 5.2, P =0.004). Risk estimates were independent of other risk factors and were similar in subgroup analyses limited to cardiovascular death (RR=2.1) or to recurrent nonfatal MI (RR=3.2). Conclusions —Plasma concentrations of TNF-α are persistently elevated among post-MI patients at increased risk for recurrent coronary events. These data support the hypothesis that a persistent inflammatory instability is present among stable patients at increased vascular risk. Novel therapies designed to attenuate inflammation may thus represent a new direction in the treatment of MI.
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Serum TNFa is greatly increased during acute coronary syndromes but is also increased to a lesser degree in stable chronic angina and is a marker of future events.
“Serum TNFa is greatly increased during acute coronary syndromes but is also increased to a lesser degree in stable chronic angina and is a marker of future events.31”
From Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life (2004) · cites this paper as [31]
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- Authors
- Ridker, P. M., Rifai, N., Pfeffer, M., Sacks, F., Lepage, S., & Braunwald, E.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders (P.M.R.), the Center for Cardiovascular Prevention (P.M.R.), Division of Cardiovascular Diseases (P.M.R., M.P., F.S., E.B.) and the Division of Preventive Medicine (P.M.R.), Brigham and Women’s Hospital; the Department of Pathology, Children’s Hospital Medical Center (N.R.), Harvard Medical School, Boston, Mass; and the Centre Universitaire de Sante de l’Estrie (S.L.), Sherbrooke, Quebec, Canada.
- Venue
- Circulation
- Published
- 2000-05-09
- Volume
- 101
- Issue
- 18
- Pages
- 2149-2153
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1997443963
- Cited by
- 934
- References
- 31
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 18 · 2023: 22 · 2022: 26 · 2021: 20 · 2020: 17 · 2019: 26 · 2018: 24 · 2017: 35 · 2016: 29 · 2015: 40 · 2014: 22 · 2013: 42 · 2012: 44
- FWCI
- 29.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- TNF-α, myocardial infarction, recurrent coronary events, cardiovascular risk, inflammation, plasma TNF-α levels, cardiovascular mortality, CARE trial, anti-inflammatory therapy
- MeSH terms
- Adult, Aged, Coronary Disease, Female, Humans, Male, Middle Aged, Myocardial Infarction, Predictive Value of Tests, Risk Factors, Tumor Necrosis Factor-alpha, Up-Regulation
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