The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index.
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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Self-citationCurrent and Future Directions in Frailty Research
Mohandas, A., Reifsnyder, J., Jacobs, M. L., & Fox, T. (2011) · Population Health Management · doi:10.1089/pop.2010.0066 · Cited by 30
“Increases in inflammatory markers in older adults have been associated with both disability and mortality.(10,11) For example, high levels of C-reactive proteins and cytokines that characterize inflammation have been associated with poorer physical function in older adults.”
Ji, J., Sun, C., Cohen, H. J., Synold, T. W., Muss, H. B., & Sedrak, M. S. (2022) · Journal of Clinical Oncology · doi:10.1200/jco.22.01217 · Cited by 28
Self-citationAdamis, D., Treloar, A. J., Gregson, N. A., Macdonald, A., & Martin, F. C. (2010) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2010.04.006 · Cited by 29
“…of identifiable disease, may have detrimental effects on the neuroendocrine system, skeletal muscle, bone, CNS, and other systems, possibly through increased production of oxygen free radicals with subsequent organ damage and systemic functional decline (Cohen et al., 2003; Krabbe et al., 2004).”
BackgroundOn the Memory of a Chronic Illness
Goldschmidt‐Clermont, P. J., & Peterson, E. D. (2003) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2003.45.re8 · Cited by 26
Pooter, N. D., Brionne‐François, M., Smahi, M., Abecassis, L., & Toulon, P. A. (2021) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.15278 · Cited by 27
Incorporating Biomarkers of Frailty and Senescence in Cancer Therapeutic Trials
Hubbard, J. M., & Jatoi, A. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu046 · Cited by 25
“(42) IL-6, D-dimer Functional decline and mortality Katz and Akpom (69), Nagi (70), Rosow and Breslau (68), instrumental activies of daily living.”
BackgroundNguyen, T. N., Morel‐Kopp, M., Pepperell, D., Cumming, R. G., Hilmer, S. N., & Wård, C. (2017) · Aging Clinical and Experimental Research · doi:10.1007/s40520-017-0733-8 · Cited by 25
“High levels of D-dimer and interleukin-6 were associated with increased mortality and functional decline (which may contribute to the development of frailty) in older people [14].”
BackgroundSchouten, L. R. A., Bos, L. D. J., Neto, A. S., van Vught, L. A., Wiewel, M. A., Hoogendijk, A. J., Bonten, M. J. M., Cremer, O. L., Horn, J., van der Poll, T., et al. (2019) · Intensive Care Medicine Experimental · doi:10.1186/s40635-019-0270-1 · Cited by 25
Geographical Segregation and IL-6: a Marker of Chronic Inflammation in Older Adults
Purser, J. L., Kuchibhatla, M. N., Miranda, M. L., Blazer, D. G., Cohen, H. J., & Fillenbaum, G. G. (2008) · Biomarkers in Medicine · doi:10.2217/17520363.2.4.335 · Cited by 23
Self-citationHemostasis and thrombosis in older adults
Gharacholou, S. M., & Becker, R. C. (2009) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-009-0308-4 · Cited by 23
“The association between elevated levels of D-dimer, a marker of fibrin formation and its subsequent degradation, and interleukin-6 (IL-6) with diminishing functional status and survival suggests that frailty may represent an intermediate phenotype of prognostic significance [9].”
BackgroundInterleukin‐6 Modulates Plasma Cholesterol and C‐Reactive Protein Concentrations in Nonagenarians
Lehtimäki, T. J., Ojala, P., Rontu, R., Goebeler, S., Karhunen, P. J., Jylhä, M. K., Mattila, K. J., Metso, S., Jokela, H., Nikkilä, M. T., et al. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53484.x · Cited by 23
“Systemic inflammation characterized by elevated IL-6 or CRP concentration is, in turn, closely associated with occurrence of congestive heart failure,(13) worse functional status,(14) cognitive decline,(15) occurrence of myocardial infarction(16) and cardiovascular disease,(12) and a risk of mortality in subjects aged…”
BackgroundPeripheral blood markers of inflammation and functional impairment in elderly community-dwellers
Ravaglia, G., Forti, P., Maioli, F., Brunetti, N. D., Martelli, M., Talerico, T., Bastagli, L., Muscari, A., & Mariani, E. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.06.010 · Cited by 22
Multiple Myeloma in the Very Old: An IASIA Conference Report
Tuchman, S. A., Shapiro, G. R., Ershler, W. B., Badros, A. Z., Cohen, H. J., Dispenzieri, A. A., Flores, I. Q., Kanapuru, B., Jurivich, D. A., Longo, D. L., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju067 · Cited by 22
“In the future, it may be possible to assess frailty with biomarkers; inflammatory cytokines such as interleukin 6, for instance, are associated with the presence of the determinants of the frailty phenotype (12,17).”
BackgroundSelf-citationC-Reactive protein and lipid parameters in older persons aged 80 years and older
Cesari, M., Onder, G., Zamboni, V., Capoluongo, E., Russo, A., Bernabei, R., Pahor, M., & Landi, F. (2009) · The journal of nutrition health & aging · doi:10.1007/s12603-009-0168-9 · Cited by 22
“Systemic inflammation characterized by elevated CRP concentrations is associated with incident cardiovascular disease(3), functional decline (4, 5 ), physical disability (6), and mortality (4, 5) in older persons.”
BackgroundClinical and inflammatory response to bloodstream infections in octogenarians
Green, J. E., Ariathianto, Y., Wong, S. M., Aboltins, C. A., & Lim, W. K. (2014) · BMC Geriatrics · doi:10.1186/1471-2318-14-55 · Cited by 21
“hypoalbuminaemia [22].”
Nguyen, T. N., Pepperell, D., Morel‐Kopp, M., Cumming, R. G., Wård, C., & Hilmer, S. N. (2016) · Cardiology and Therapy · doi:10.1007/s40119-016-0056-4 · Cited by 21
Mayot, G., Vidal, K., MARTIN, J., Breuillé, D., Blum, S., Obled, C., & Papet, I. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.01.003 · Cited by 21
The Relationship Between Functional Status and Inflammatory Disease in Older Adults
Thomas, D. R. (2003) · The Journals of Gerontology Series A · doi:10.1093/gerona/58.11.m995 · Cited by 21
Inflammatory biomarkers, multi-morbidity, and biologic aging
Sauver, J. L. S., Rocca, W. A., LeBrasseur, N. K., Chamberlain, A. M., Olson, J. E., Jacobson, D. J., McGree, M. E., & Mielke, M. M. (2022) · Journal of International Medical Research · doi:10.1177/03000605221109393 · Cited by 20
Cesari, M., Marzetti, E., Laudisio, A., Antonica, L., Pahor, M., Bernabei, R., & Zuccalà, G. (2009) · Age and Ageing · doi:10.1093/ageing/afp194 · Cited by 19
“The age-related increase of systemic inflammation has been associated with a wide spectrum of biological, clinical and functional outcomes, including frailty and mortality [2].”
BackgroundLustosa, L. P., Coelho, F. M., da Silva, J. P., Pereira, D. S., Parentoni, A. N., Dias, J. M. D., Dias, R. C., & Pereira, L. S. (2010) · Trials · doi:10.1186/1745-6215-11-82 · Cited by 19
“This release may bring a benefit by decreasing TNF-a levels [3,6-8,10,12,13].”
BackgroundPlatelet count kinetics following interruption of antiretroviral treatment
Zetterberg, E., Neuhaus, J., Baker, J. V., Somboonwit, C., Llibre, J. M., Palfreeman, A., Chini, M., & Lundgren, J. D. (2012) · AIDS · doi:10.1097/qad.0b013e32835a104d · Cited by 18
Physical functioning related to C-reactive protein and fibrinogen levels in mid-life women
Tomey, K., Sowers, M. R., Zheng, H. T., & Jackson, E. A. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.10.002 · Cited by 17
“…association between thrombotic blood markers and physical functioning, however, have been mixed with some studies finding that higher levels of these markers are associated with poorer functioning (McDermott et al., 2004; Cohen et al., 2003) and some finding no association (McDermott et al., 2005).”
ResultChenevier‐Gobeaux, C., Trabattoni, E., Elfassy, Y., Picard, C., Guérin, S., Borderie, D., & Claessens, Y.-É. (2012) · Biomarkers · doi:10.3109/1354750x.2012.685953 · Cited by 17
“As ageing is associated to changes in several biochemical parameters including inflammation proteins (Cohen et al., 2003; Singh, 2011), we aimed to investigate whether procalcitonin”
BackgroundScreening for frailty among older patients with cancer using blood biomarkers of inflammation
Harneshaug, M., Kirkhus, L., Benth, J. Š., Grønberg, B. H., Bergh, S., Whist, J. E., Rostoft, S., & Slaaen, M. (2018) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2018.07.003 · Cited by 17
Fragilidad en el adulto mayor: Un primer acercamiento
Ramos, G. E. L., & Rodríguez, J. J. L. (2004) · Revista cubana de medicina general integral · Cited by 17
FRAILTY JUDGMENT BY HOSPITAL TEAM MEMBERS: DEGREE OF AGREEMENT AND SURVIVAL PREDICTION
Herrmann, F. R., Osiek, A., Cos, M., Michel, J., & Robine, J. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53278_6.x · Cited by 17
Adjuvant Therapy in Elderly Patients with Breast Cancer
Biganzoli, L., Aapro, M., Balducci, L., Crivellari, D., Minisini, A. M., & Piccart, M. J. (2004) · Clinical Breast Cancer · doi:10.3816/cbc.2004.n.022 · Cited by 17
Liu, P., Pan, Y., Song, Y., Zhou, Y., Zhang, W., Li, X., Li, J., Li, Y., & Ma, L. (2023) · European journal of medical research · doi:10.1186/s40001-023-01017-6 · Cited by 16
“Those with high interleukin-6 and high D-dimer levels had the greatest functional declines [32].”
BackgroundBiological risk of older adults with visual impairments
Steinman, B. A., & Vasunilashorn, S. M. (2010) · The journal of nutrition health & aging · doi:10.1007/s12603-010-0296-2 · Cited by 16
“Several biomarkers have been associated with higher rates of mortality (12), reduced cognitive (13) and physical ( 14 ) functioning, and heart disease (15), and are generally viewed as good indicators of the health status of older people (16), without regard to vision”
BackgroundJeong, S. J., Yoon, S. S., Han, S. H., Yong, D., Kim, C. O., & Kim, J. M. (2013) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2013.07.001 · Cited by 16
Multimodal clocks of human aging
Li, J., Jiang, B., Zhang, W., Hao, J., Liu, Z., Ji, Q., Zheng, Y., Lu, X., Zheng, Z., Ma, S., et al. (2026) · Cell · doi:10.1016/j.cell.2026.04.025 · Cited by 19
Adjuvant Chemotherapy for Breast Cancer in Older Women: Emerging Evidence to Aid in Decision Making
Kimmick, G. G. (2011) · Current Treatment Options in Oncology · doi:10.1007/s11864-011-0159-z · Cited by 15
“patients with cancer may be limited by the concurrent effects of the cancer and its treatment on these blood markers [54, 55 ].”
BackgroundMcClure, C. K., Khoudary, S. R. E., Karvonen-Gutierrez, C. A., Ylitalo, K. R., Tomey, K., VoPham, T., Sternfeld, B., Cauley, J. A., & Harlow, S. D. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.10.016 · Cited by 14
“In cross-sectional and longitudinal studies of older adults, higher levels of proinflammatory cytokines (Cesari et al., 2004; Cohen et al., 2003; Ferrucci et al., 2002; Figaro et al., 2006; Penninx et al., 2004; Tiainen et al., 2010; Walston et al., 2002) and markers of hemostasis (Barzilay et al.,…”
BackgroundInfluential
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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