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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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Senior Adult Oncology Clinical Practice Guidelines in Oncology
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Self-citationPhysical Activity, Sedentary Behavior, and Inflammatory and Hemostatic Markers in Men
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“been implicated in the development of atherosclerosis, and higher levels of markers such as D-dimer have been associated with greater declines in physical function (4).”
BackgroundDrotrecogin Alfa (Activated) Treatment of Older Patients with Severe Sepsis
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“Indeed, recent studies have found that there are agerelated systemic inflammatory and coagulopathic changes that may increase vulnerability among older patients who develop severe sepsis [33–36].”
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“Some have shown no benefit to bone with EFA supplementation,8 whereas others have demonstrated higher BMD in communities with greater fish intake9 or lower bone turnover with fish oil intake.10,11 Recently, a small longitudinal study of young men found more bone accretion in those with higher DHA levels,12 and evidenc…”
BackgroundMa, D., Jasinska, A. J., Feyertag, F., Wijewardana, V., Kristoff, J., He, T., Raehtz, K. D., Schmitt, C. A., Jung, Y., Cramer, J. D., et al. (2014) · Journal of Virology · doi:10.1128/jvi.03606-13 · Cited by 86
“This is not surprising, as an age-related increase in coagulability that is reflected in higher levels of D dimer occurs in humans (100, 101).”
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“with levels of both in the highest quartile, as compared with thosewhowerenot in either of thehighest quartiles.(46) Data from the Newcastle 85+ Study (n = 845 subjects, age ≥ 85 years) confirmed the association between frailty and IL-6, TNF-alpha, CRP and neutrophil count in the very old.”
Biomarkers of Immune Dysfunction Following Combination Antiretroviral Therapy for HIV Infection
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“Several possible parameters of allostatic load have already been proposed, including indices of the hypothalamic-pituitary-adrenal axis, cardiovascular and sympathetic nervous systems, glucose dysregulation, chronic inflammation, and coagulation.(2,4,45) Although each biomarker alone is thought to indicate physiologic…”
BackgroundSelf-citationHematologic Changes in Sepsis and Their Therapeutic Implications
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“These hemostatic alterations may be linked to increased frailty and functional impairment in the elderly.(87) Further activation of the hemostatic system of the aged can be produced by bacterial products released during sepsis.”
BackgroundDepression and Frailty: The Need for Multidisciplinary Research
Katz, I. R. (2004) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200401000-00001 · Cited by 80
Anemia in the elderly—Clinical findings and impact on health
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Incorporating Biomarkers Into Cancer and Aging Research
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“increased chronic inflammatory and procoagulant markers predict functional decline.(15-19,45,46) In an analysis of moderately to severely”
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The frail renin–angiotensin system
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Cardiovascular implications from untreated human immunodeficiency virus infection
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“D-dimer levels are associated with functional decline, as well as mortality, in elderly patients.(38) The pronounced D-dimer odds ratios for all-cause mortality among participants in SMART”
BackgroundAdjuvant Therapy in the Elderly: Making the Right Decision
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Inflammation and mortality in a frail mouse model
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Presepsin (sCD14-ST) in emergency department: The need for adapted threshold values?
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Serious Non-AIDS events: Immunopathogenesis and interventional strategies
Hsu, D. C., Sereti, I., & Ananworanich, J. (2013) · AIDS Research and Therapy · doi:10.1186/1742-6405-10-29 · Cited by 73
“High levels of biomarkers associated with inflammation (C-reactive protein, CRP, and IL-6) and coagulopathy (D-dimer and fibrinogen) are associated with increased risk of cardiovascular disease [77-80], increased cancer risks [81-83] and mortality [80,84-86] in the general population.”
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“Increased levels of plasma D-dimer, a marker of ongoing coagulation and fibrinolysis, have also been linked to these outcomes [8, 11].”
The Clinical Care of Frail, Older Adults
Ko, F. (2010) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.08.007 · Cited by 75
Prevalence of aging population in the Middle East and its implications on cancer incidence and care
Hajjar, R. R., Atlı, T., Al-Mandhari, Z., Oudrhiri, M. Y., Balducci, L., & Silbermann, M. (2013) · Annals of Oncology · doi:10.1093/annonc/mdt268 · Cited by 73
Is There a Biomedical Explanation for Socioeconomic Differences in Incident Mobility Limitation?
Koster, A., Penninx, B. W. J. H., Bosma, H., Kempen, G. I. J. M., Harris, T. B., Newman, A. B., Rooks, R. N., Rubin, S. M., Simonsick, E. M., van Eijk, J. T. M., et al. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.8.1022 · Cited by 71
Self-citation
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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