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Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly
Abstract
Purpose This study was performed to determine the effects of markers of inflammation (interleukin 6) and coagulation (D-dimer) on mortality and functional status in older persons.Methods Subjects were selected for the Duke Established Populations for Epidemiologic Studies of the Elderly. In 1992, 2569 subjects (age >71 years) were interviewed, of whom 1,723 had interleukin-6 and D-dimer measurements. Values of interleukin 6 and D-dimer were categorized into quartiles. Outcomes were mortality (through 5 years) and functional status (through 4 years). Relative risks were estimated with proportional hazards models that adjusted for potential confounders.Results The relative risk of mortality was 1.28 (95% confidence interval [CI]: 0.98 to 1.69; P = 0.06) for those with only interleukin-6 levels in the highest quartile, 1.53 (95% CI: 1.18 to 1.97; P = 0.001) for subjects with only D-dimer levels in the highest quartile, and 2.00 (95% CI: 1.53 to 2.62; P = 0.0001) for those with levels of both in the highest quartile, as compared with those who were not in either of the highest quartiles. Those with high interleukin-6 and high D-dimer levels had the greatest declines in all measures of function.Conclusion Activation of the coagulation and inflammatory pathways is associated with mortality and decline in function, and may be part of the explanation for the development of a frailty phenotype in the elderly.
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“In particular, an increase in the basal production of proinflammatory cytokines, observed in different cell types, could be a major contributor to the age-related increase of the levels of such molecules observed in several cohorts of elderly subjects [19, 67, 68].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [68]
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Metadata
- Authors
- Cohen, H. J., Harris, T., & Pieper, C. F.
- Affiliations
- Duke University (US)
- National Institutes of Health (US)
- Corresponding author
- Cohen, Harvey Jay
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 114
- Issue
- 3
- Pages
- 180-187
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W1994696327
- Cited by
- 327
- References
- 53
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 14 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 7 · 2017: 13 · 2016: 19 · 2015: 14 · 2014: 18 · 2013: 19 · 2012: 19
- FWCI
- 10.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01ag012102-011)
- National Institute on Aging (R01AG012765, N01‐AG12102, P60AG011268)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Aging, Health, and Disability
- Keywords
- interleukin-6, D-dimer, coagulation, inflammation, mortality, functional decline, frailty, older adults, inflammatory markers
- MeSH terms
- Activities of Daily Living, Aged, Aged, 80 and over, Black or African American, Blood Coagulation, Cardiovascular Diseases, Cause of Death, Diabetes Mellitus, Female, Fibrin Fibrinogen Degradation Products, Humans, Inflammation, Longitudinal Studies, Male, Neoplasms, North Carolina, Smoking, Biomarkers, Interleukin-6, Multivariate Analysis, Frail Elderly, Sex Distribution, Pulmonary Disease, Chronic Obstructive, Black People, White People
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