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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An increase in basal production of proinflammatory cytokines in different cell types could be a major contributor to the age-related increase of these molecules in elderly cohorts.
“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]
Cites
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793 · see citing works
Regression Models and Life-Tables
Cox, D. R. (1992) · Springer Series in Statistics · doi:10.1007/978-1-4612-4380-9_37 · Cited by 26,297 · see citing works
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725 · see citing works
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734 · see citing works
Protective and Damaging Effects of Stress Mediators
McEwen, B. S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801153380307 · Cited by 6,733 · see citing works
Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis
Bernard, G. R., Vincent, J., Laterre, P., LaRosa, S. P., Dhainaut, J.-F., Lopez-Rodriguez, A., Steingrub, J. S., Garber, G. E., Helterbrand, J. D., Ely, E. W., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103083441001 · Cited by 6,124 · see citing works
Ridker, P. M., Hennekens, C. H., Buring, J. E., & Rifai, N. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003233421202 · Cited by 5,850 · see citing works
Hemodynamic shear stress and its role in atherosclerosis
Malek, A. M. (1999) · JAMA · doi:10.1001/jama.282.21.2035 · Cited by 3,650 · see citing works
Quality of life and pharmacoeconomics in clinical trials
Pater, J. L. (1996) · Controlled Clinical Trials · doi:10.1016/s0197-2456(97)82191-5 · Cited by 2,412 · see citing works
Danesh, J., Collins, R., Appleby, P. N., & Peto, R. (1998) · JAMA · doi:10.1001/jama.279.18.1477 · Cited by 2,027 · see citing works
Quality of life and pharmacoeconomics in clinical trials
Spilker, B. (1996) · DigitalGeorgetown (Georgetown University Library) · Cited by 1,862 · see citing works
Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly
Harris, T. B., Ferrucci, L., Tracy, R. P., Corti, M. C., Wacholder, S., Ettinger, W. H., Heimovitz, H., Cohen, H. J., & Wallace, R. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00066-2 · Cited by 1,488 · see citing works
Self-citationAn epidemiology of disability among adults in the United States.
Nagi, S. Z. (1976) · The Milbank Memorial Fund Quarterly. Health and Society · doi:10.2307/3349677 · Cited by 1,431 · see citing works
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282 · see citing works
A Measure of Primary Sociobiological Functions
Katz, S., & Akpom, C. A. (1976) · International Journal of Health Services · doi:10.2190/uurl-2ryu-wryd-ey3k · Cited by 1,232 · see citing works
Lindahl, B., Toss, H., Siegbahn, A., Venge, P., & Wallentin, L. C. (2000) · New England Journal of Medicine · doi:10.1056/nejm200010193431602 · Cited by 1,221 · see citing works
A Guttman Health Scale for the Aged
Rosow, I., & Breslau, N. (1966) · Journal of Gerontology · doi:10.1093/geronj/21.4.556 · Cited by 1,132 · see citing works
Principles of Geriatric Medicine and Gerontology.
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-9-817_6 · Cited by 1,056 · see citing works
Serum IL‐6 Level and the Development of Disability in Older Persons
Ferrucci, L., Harris, T. B., Guralnik, J. M., Tracy, R. P., Corti, M., Cohen, H. J., Penninx, B., Pahor, M., Wallace, R., & Havlik, R. J. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb01583.x · Cited by 809 · see citing works
Self-citationPlasminogen-Activator Inhibitor Type 1 and Coronary Artery Disease
Kohler, H. P., & Grant, P. J. (2000) · New England Journal of Medicine · doi:10.1056/nejm200006153422406 · Cited by 805 · see citing works
Bone, R. C. (1996) · Annals of Internal Medicine · doi:10.7326/0003-4819-125-8-199610150-00009 · Cited by 718 · see citing works
Tracy, R. P., Psaty, B. M., Macy, E., Bovill, E. G., Cushman, M., Cornell, E. S., & Kuller, L. H. (1997) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.17.10.2167 · Cited by 539 · see citing works
The Association of Plasma IL-6 Levels With Functional Disability in Community-Dwelling Elderly
Cohen, H. J., Pieper, C. F., Harris, T., Rao, K. M. K., & Currie, M. S. (1997) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/52a.4.m201 · Cited by 476 · see citing works
Self-citationToward an Understanding of Frailty
Hamerman, D. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-11-199906010-00022 · Cited by 441 · see citing works
Taaffe, D. R., Harris, T. B., Ferrucci, L., Rowe, J., & Seeman, T. E. (2000) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/55.12.m709 · Cited by 438 · see citing works
Self-citationEstablished Populations for Epidemiologic Studies of the Elderly: Resource Data Book
Kaplan, G. A. (1987) · Journal of Gerontology · doi:10.1093/geronj/42.6.688a · Cited by 421 · see citing works
Established populations for epidemiologic studies of the elderly: Study design and methodology
Cornoni‐Huntley, J. C., Ostfeld, A. M., Taylor, J. O., Wallace, R. B., Blazer, D. G., Berkman, L. F., Evans, D. A., Kohout, J., Lemke, J. H., Scherr, P. A., et al. (1993) · Aging Clinical and Experimental Research · doi:10.1007/bf03324123 · Cited by 326 · see citing works
Principles of Geriatric Medicine and Gerontology
Kerins, G. (2000) · JAMA · doi:10.1001/jama.283.7.930 · Cited by 319 · see citing works
Reuben, D. B., Cheh, A. I., Harris, T. B., Ferrucci, L., Rowe, J. W., Tracy, R. P., & Seeman, T. E. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50157.x · Cited by 296 · see citing works
Self-citationInflammatory Markers of Coronary Risk
Rader, D. J. (2000) · New England Journal of Medicine · doi:10.1056/nejm200010193431609 · Cited by 260 · see citing works
Fibrinolytic Activation Markers Predict Myocardial Infarction in the Elderly
Cushman, M., Lemaître, R. N., Kuller, L. H., Psaty, B. M., Macy, E. M., Sharrett, A. R., & Tracy, R. P. (1999) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.19.3.493 · Cited by 250 · see citing works
Ridker, P. M., Hennekens, C. H., Cerskus, A. L., & Stampfer, M. J. (1994) · Circulation · doi:10.1161/01.cir.90.5.2236 · Cited by 243 · see citing works
Phylogenetic and functional relationships between coagulation and the innate immune response
Opal, S. M. (2000) · Critical Care Medicine · doi:10.1097/00003246-200009001-00017 · Cited by 179 · see citing works
Stress-Induced Immunomodulation
Glaser, R., Rabin, B. S., Chesney, M. A., Cohen, S., & Natelson, B. H. (1999) · JAMA · doi:10.1001/jama.281.24.2268 · Cited by 160 · see citing works
Pieper, C. F., Rao, K. M. K., Currie, M. S., Harris, T. B., & Cohen, H. J. (2000) · The Journals of Gerontology Series A · doi:10.1093/gerona/55.11.m649 · Cited by 138 · see citing works
Self-citationModulation of hemostatic mechanisms in bacterial infectious diseases
Tapper, H., & Herwald, H. (2000) · Blood · doi:10.1182/blood.v96.7.2329 · Cited by 123 · see citing works
Biologic markers as predictors of cardiovascular disease
Frishman, W. H. (1998) · The American Journal of Medicine · doi:10.1016/s0002-9343(98)00184-3 · Cited by 122 · see citing works
Kempen, G. I. J. M., Myers, A. M., & Powell, L. E. (1995) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(95)00043-7 · Cited by 100 · see citing works
Rao, K. M. K., Pieper, C. F., Currie, M. S., & Cohen, H. J. (1994) · American Journal of Clinical Pathology · doi:10.1093/ajcp/102.6.802 · Cited by 98 · see citing works
Self-citationEditorial: In Search of the Underlying Mechanisms of Frailty
Cohen, H. J. (2000) · The Journals of Gerontology Series A · doi:10.1093/gerona/55.12.m706 · Cited by 82 · see citing works
Self-citationCorrelates of Thrombin Markers in an Elderly Cohort Free of Clinical Cardiovascular Disease
Cushman, M., Psaty, B. M., Macy, E., Bovill, E. G., Cornell, E. S., Kuller, L. H., & Tracy, R. P. (1996) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.16.9.1163 · Cited by 71 · see citing works
Trotta, R. F., Diehl, L. F., Shorr, A. F., Hanzel, G. S., & Alkins, S. A. (1999) · Intensive Care Medicine · doi:10.1007/s001340050817 · Cited by 70 · see citing works
Hamaguchi, M., Morishita, Y., Takahashi, I., Ogura, M., Takamatsu, J., & Saito, H. (1991) · Blood · doi:10.1182/blood.v77.1.94.94 · Cited by 58 · see citing works
Edgington, T. S., Curtiss, L. K., & Plow, E. F. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.134.1.471 · Cited by 57 · see citing works
Regulation of Plasminogen Gene Expression by Interleukin-6
Jenkins, G. R., Seiffert, D., Parmer, R. J., & Miles, L. A. (1997) · Blood · doi:10.1182/blood.v89.7.2394 · Cited by 56 · see citing works
Nutrition, Immunity, and Infection in Infants and Children
Suskind, R. M., Tontisirin, K., & Services, N. N. (2001) · Cited by 53 · see citing works
Hamerman, D., Berman, J. W., Albers, G. W., Brown, D. L., & Silver, D. A. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb01299.x · Cited by 41 · see citing works
Kazura, J. W., Wenger, J. D., Salata, R. A., Budzynski, A. Z., & Goldsmith, G. H. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114098 · Cited by 34 · see citing works
Currie, M. S., Rao, K. M. K., Blazer, D. G., & Cohen, H. J. (1994) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1994.tb06534.x · Cited by 33 · see citing works
Self-citationSerum Levels of IL‐6 and Development of Disability in Older Persons
Kuller, L. H. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb01604.x · Cited by 26 · see citing works
Stress-Induced Immunomodulation
Petticrew, M. P., & Hunter, D. (1999) · JAMA · doi:10.1001/jama.282.23.2209 · Cited by 19 · see citing works
Atherosclerosis and the Immune System
Bittner, V. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.13.1395 · Cited by 16 · see citing works
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Validity and reliability of the Edmonton Frail Scale
Rolfson, D. B., Majumdar, S. R., Tsuyuki, R. T., Tahir, A., & Rockwood, K. (2006) · Age and Ageing · doi:10.1093/ageing/afl041 · Cited by 1,643 · see citing works
“The precision and clarity in definition of this tool is attractive, and it appears to correlate with specific physiological alterations, particularly enhanced inflammation and coagulation [15], as have other measures [16, 17].”
Background. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.
Kuller, L. H., Tracy, R., Belloso, W., Wit, S. D., Drummond, F., Lane, H. C., Ledergerber, B., Lundgren, J., Neuhaus, J., Nixon, D., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050203 · Cited by 1,617 · see citing works
“Associations of D-dimer and IL-6 with all-cause mortality have been reported in other studies that included non-HIVinfected participants [15,23,33].”
Use of comprehensive geriatric assessment in older cancer patients:
Extermann, M., Aapro, M., Bernabei, R., Cohen, H. J., Droz, J.-P., Lichtman, S., Mor, V., Monfardini, S., Repetto, L., Sørbye, L., et al. (2005) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.06.003 · Cited by 1,098 · see citing works
“A s 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 [7].”
BackgroundSelf-citationAge-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061 · see citing works
Inflammatory markers in population studies of aging
Singh, T., & Newman, A. B. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.11.002 · Cited by 866 · see citing works
Frailty Syndrome: A Transitional State in a Dynamic Process
Lang, P. O., Michel, J., & Zekry, D. (2009) · Gerontology · doi:10.1159/000211949 · Cited by 672 · see citing works
“Similarly, the Duke Established Populations for Epidemiologic Studies of the Elderly, a 5-year follow-up of 1,723 subjects of 71 years and over, demonstrated that the combination of the highest quartiles of IL-6 and high D-dimer blood levels doubled the relative risk of death over 5 years [”
MethodD-dimer antigen: current concepts and future prospects
Adam, S. S., Key, N. S., & Greenberg, C. S. (2008) · Blood · doi:10.1182/blood-2008-06-165845 · Cited by 680 · see citing works
Human innate immunosenescence: causes and consequences for immunity in old age
Panda, A., Arjona, A., Sapey, E., Bai, F., Fikrig, E., Montgomery, R. R., Lord, J. M., & Shaw, A. C. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.004 · Cited by 502 · see citing works
Tagalakis, V., Patenaude, V., Kahn, S. R., & Suissa, S. (2013) · The American Journal of Medicine · doi:10.1016/j.amjmed.2013.02.024 · Cited by 464 · see citing works
The Immunopathogenesis of Sepsis in Elderly Patients
Opal, S. M., Girard, T. D., & Ely, E. W. (2005) · Clinical Infectious Diseases · doi:10.1086/432007 · Cited by 461 · see citing works
“tribute to poor clearance of fibrin from the circulation of elderly persons [54].”
BackgroundResultInfluentialAging of the immune system: Focus on inflammation and vaccination
Pinti, M., Appay, V., Campisi, J., Frasca, D., Fülöp, T., Sauce, D., Larbi, A., Weinberger, B., & Cossarizza, A. (2016) · European Journal of Immunology · doi:10.1002/eji.201546178 · Cited by 439 · see citing works
Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature
Beghé, C., Wilson, A., & Ershler, W. B. (2004) · The American Journal of Medicine · doi:10.1016/j.amjmed.2003.12.009 · Cited by 450 · see citing works
. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty.
Desquilbet, L., Jacobson, L. P., Fried, L. P., Phair, J. P., Jamieson, B. D., Holloway, M., Margolick, J. B., & Study, F. T. M. A. C. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.11.1279 · Cited by 420 · see citing works
“Consequently, it has been hypothesized that IL-6 may causally contribute to the aging process (56,63,64) and/or to the syndrome of frailty (62).”
BackgroundModels, Definitions, and Criteria of Frailty
Hogan, D. B. (2006) · Elsevier eBooks · doi:10.1016/b978-012369391-4/50051-5 · Cited by 410 · see citing works
“A low level of chronic inflammation secondary to age-related dysregulation of the immune system has also been proposed as the underlying cause of frailty (126-129).”
BackgroundSoto‐Pérez‐de‐Celis, E., Li, D., Yuan, Y., Lau, Y. M., & Hurria, A. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30348-6 · Cited by 412 · see citing works
Inflammation and frailty measures in older people
Hubbard, R. E., O’Mahony, M. S., Savva, G. M., Calver, B. L., & Woodhouse, K. W. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00733.x · Cited by 393 · see citing works
“Increased levels of IL-6 have been linked to physical decline and disability [36, 37], and the development of age-related conditions such as dementia, Parkinson’s disease, atherosclerosis and type 2 diabetes is associated with elevated levels of inflammatory mediators [38].”
BackgroundSkeletal muscle and mortality results from the InCHIANTI study
Cesari, M., Pahor, M., Lauretani, F., Zamboni, V., Bandinelli, S., Bernabei, R., Guralnik, J. M., & Ferrucci, L. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/gln031 · Cited by 346 · see citing works
Endocrine and inflammatory markers as predictors of frailty
Puts, M. T. E., Visser, M., Twisk, J. W. R., Deeg, D. J. H., & Lips, P. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02355.x · Cited by 316 · see citing works
Interconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 310 · see citing works
“High serum levels of coagulation factors such as D-dimer (a fibrin degradation product) are associated with functional decline and increased mortality in older persons [114,115].”
BackgroundImmunosenescence and vaccine failure in the elderly
Grubeck-Loebenstein, B., Della Bella, S., Iorio, A. M., Michel, J.-P., Pawelec, G., & Solana, R. (2009) · Aging Clinical and Experimental Research · doi:10.1007/bf03324904 · Cited by 269 · see citing works
Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women
Hackett, R. A., Hamer, M., Endrighi, R., Brydon, L., & Steptoe, A. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.016 · Cited by 272 · see citing works
“, 2009), and IL-6 also predicts cognitive and physical decline at older ages (Weaver et al., 2002; Cohen et al., 2003).”
BackgroundLeng, S. X., Cappola, A. R., Andersen, R. E., Blackman, M. R., Koenig, K., Blair, M., & Walston, J. D. (2004) · Aging Clinical and Experimental Research · doi:10.1007/bf03324545 · Cited by 270 · see citing works
Evaluating the Older Patient with Cancer: Understanding Frailty and the Geriatric Assessment
Pal, S. K., Katheria, V., & Hurria, A. (2010) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20059 · Cited by 258 · see citing works
The clinical implications of ageing for rational drug therapy
Shi, S., Mörike, K., & Klotz, U. (2008) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-007-0422-1 · Cited by 244 · see citing works
“The biological alterations of frailty are associated with an increased vulnerability for diseases, mortality and functional decline and may be part of the explanation for the development of a frail phenotype [52–55].”
BackgroundInteraction between Comorbidity and Cancer
Extermann, M. (2007) · Cancer Control · doi:10.1177/107327480701400103 · Cited by 214 · see citing works
Role of CMV in immune senescence.
Pawelec, G., & Derhovanessian, E. (2011) · Virus Research · doi:10.1016/j.virusres.2010.09.010 · Cited by 201 · see citing works
Novel loci and pathways significantly associated with longevity
Zeng, Y., Nie, C., Min, J., Liu, X., Li, M., Chen, H., Xu, H., Wang, M., Ni, T., Li, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep21243 · Cited by 195 · see citing works
Risk of Frailty in Elderly With COPD: A Population-Based Study
Lahousse, L., Ziere, G. J., Verlinden, V. J. A., Zillikens, M. C., Uitterlinden, A. G., Rivadeneira, F., Tiemeier, H. W., Joos, G., Albert Hofman, D., Ikram, M. A., et al. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glv154 · Cited by 201 · see citing works
Insights into Severe Sepsis in Older Patients: From Epidemiology to Evidence-Based Management
Girard, T. D., Opal, S. M., & Ely, E. W. (2005) · Clinical Infectious Diseases · doi:10.1086/427876 · Cited by 197 · see citing works
“In addition, increasing age is associated with rising circulating levels of IL6 and D-dimer [17], activated factor VII, and other coagulation factors [18], indicating activation of inflammatory and coagulation pathways.”
Backgroundvon Känel, R., Dimsdale, J. E., Mills, P. J., Ancoli-Israel, S., Patterson, T. L., Mausbach, B. T., & Grant, I. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.9.963 · Cited by 196 · see citing works
“The proinflammatory cytokine interleukin (IL)-6, the acute phase reactant C-reactive protein (CRP), and the procoagulant molecule D-dimer all increase with age, and elevated plasma levels of these three measures have also been identified as biological accompaniments of frailty (8,9).”
BackgroundAffective reactivity to daily stressors is associated with elevated inflammation
Sin, N. L., Graham-Engeland, J. E., Ong, A. D., & Almeida, D. M. (2015) · Health Psychology · doi:10.1037/hea0000240 · Cited by 188 · see citing works
Hallmarks of aging and immunosenescence: Connecting the dots
Rodrigues, L. P., Teixeira, V. R., Alencar‐Silva, T., Simonassi-Paiva, B., Pereira, R. W., Pogue, R. E., & Carvalho, J. L. (2021) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2021.01.006 · Cited by 187 · see citing works
Boxer, R. S., Dauser, D., Walsh, S. J., Hager, W. D., & Kenny, R. A. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01601.x · Cited by 186 · see citing works
The Frailty Syndrome: A Comprehensive Review
Heuberger, R. (2011) · Journal of Nutrition in Gerontology and Geriatrics · doi:10.1080/21551197.2011.623931 · Cited by 187 · see citing works
Aging, Frailty, and Chemotherapy
Balducci, L. (2007) · Cancer Control · doi:10.1177/107327480701400102 · Cited by 184 · see citing works
Sepsis and Immunosenescence in the Elderly Patient: A Review
Martín, S., Pérez, A. I. B., & Aldecoa, C. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00020 · Cited by 184 · see citing works
“This leads to an increased risk of thrombosis and decreased clearance of circulating fibrin (31, 41).”
BackgroundMeasures of lower body function and risk of mortality over 7 years of follow-up
Ostir, G. V., Kuo, Y.-F., Berges, I. M., Markides, K. S., & Ottenbacher, K. J. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm121 · Cited by 165 · see citing works
Yeom, H. A., Fleury, J., & Keller, C. S. (2008) · Geriatric Nursing · doi:10.1016/j.gerinurse.2007.07.002 · Cited by 166 · see citing works
Inflammation, Coagulation, and the Pathway to Frailty
Kanapuru, B., & Ershler, W. B. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.01.030 · Cited by 163 · see citing works
Immunosenenescence: role of cytomegalovirus
Pawelec, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.11.010 · Cited by 163 · see citing works
“unosenenescence: Role of c documented as associating with morbidity and mortality (Bruunsgaard and Pedersen, 2003; Cohen et al., 2003).”
Frailty in the elderly: contributions of sarcopenia and visceral protein depletion
VanItallie, T. B. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00297-x · Cited by 161 · see citing works
Baker, J. V., Neuhaus, J., Duprez, D. A., Kuller, L. H., Tracy, R. P., Belloso, W. H., Wit, S. D., Drummond, F., Lane, H. C., Ledergerber, B., et al. (2010) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e3181f7f61a · Cited by 161 · see citing works
Sepsis in Old Age: Review of Human and Animal Studies
Starr, M. E. (2014) · Aging and Disease · doi:10.14336/ad.2014.0500126 · Cited by 154 · see citing works
“Additionally, while advancing age is associated with heightened coagulation [40, 50], the propensity for this chronic condition to worsen coagulation during sepsis is unknown [2].”
BackgroundCarreca, I. U., Balducci, L., & Extermann, M. (2005) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2005.04.012 · Cited by 153 · see citing works
Wu, H. Y., & Nguyen, G. C. (2010) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2010.05.014 · Cited by 151 · see citing works
Franchini, M. (2006) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2006.06.004 · Cited by 145 · see citing works
“[109] recently emonstrated in 1723 subjects aged over 71 years old that ctivation of coagulation and inflammation, reflected by Dimer and interleukin-6 levels, is accompanied by mortality nd functional decline.”
BackgroundChange in Frailty and Risk of Death in Older Persons
Buchman, A. S., Wilson, R. S., Bienias, J. L., & Bennett, D. A. (2009) · Experimental Aging Research · doi:10.1080/03610730802545051 · Cited by 140 · see citing works
“Many cross-sectional studies suggest that frailty increases with age and that women and those with less education are more frail (Boyd et al., 2005; Cohen et al., 2003; Fried et al., 2001; Mitnitski, Mogilner, MacKnight, & Rockwood, 2002; Newman et al., 2001; Ostir et al., 2004; Puts et al., 2005;…”
BackgroundNeutrophils in aging and aging‐related pathologies
Avondt, K. V., Strecker, J., Tulotta, C., Minnerup, J., Schulz, C., & Soehnlein, O. (2022) · Immunological Reviews · doi:10.1111/imr.13153 · Cited by 146 · see citing works
Management of cancer in the elderly.
Balducci, L. (2006) · PubMed · Cited by 141 · see citing works
Demographics, phenotypic health characteristics and genetic analysis of centenarians in China
Zeng, Y., Feng, Q., Gu, D., & Vaupel, J. W. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.12.010 · Cited by 137 · see citing works
Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk
Joseph, C., Kenny, R. A., Taxel, P., Lorenzo, J., Duque, G., & Kuchel, G. A. (2005) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2005.01.004 · Cited by 134 · see citing works
Hodes, R. J., Sierra, F., Austad, S. N., Epel, E., Neigh, G. N., Erlandson, K. M., Schafer, M. J., LeBrasseur, N. K., Wiley, C., Campisi, J., et al. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13299 · Cited by 132 · see citing works
Self-citationde Gonzalo‐Calvo, D., de Luxán‐Delgado, B., Rodríguez‐González, S., Macia, M. G., Suárez, F. M., Solano, J. J., Rodríguez‐Colunga, M. J., & Coto‐Montes, A. M. (2012) · Cytokine · doi:10.1016/j.cyto.2012.01.005 · Cited by 129 · see citing works
“Moreover, subjects with high levels of IL-6 display the greatest declines in functional dependence based on KI after 4 years of follow-up [24].”
BackgroundPoor Sleep Quality and Functional Decline in Older Women
Spira, A. P., Covinsky, K. E., Rebok, G. W., Punjabi, N. M., Stone, K. L., Hillier, T. A., Ensrud, K. E., & Yaffe, K. S. (2012) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2012.03968.x · Cited by 127 · see citing works
“Poor sleep has been linked to inflammatory processes,(22,23) which are associated with muscle loss and functional decline.(24,25) Studies are needed that investigate inflammation as a mediator of the association between objectively measured sleep and functional decline.”
BackgroundFrailty has a stronger association with inflammation than age in older veterans
Epps, P. V., Oswald, D., Higgins, P. A., Hornick, T. R., Aung, H., Banks, R. E., Wilson, B. M., Burant, C., Gravenstein, S., & Canaday, D. H. (2016) · Immunity & Ageing · doi:10.1186/s12979-016-0082-z · Cited by 124 · see citing works
“Prior studies have linked D-dimer and other markers of activated coagulation with limitation in functional abilities [4, 35].”
Altered immune system in frailty: Genetics and diet may influence inflammation
Pansarasa, O., Pistono, C., Davin, A., Bordoni, M., Mimmi, M. C., Guaita, A., & Cereda, C. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100935 · Cited by 121 · see citing works
Frailty and Its Potential Relevance to Cardiovascular Care
Singh, M., Alexander, K. P., Roger, V. L., Rihal, C. S., Whitson, H. E., Lerman, A., Jahangir, A., & Nair, K. S. (2008) · Mayo Clinic Proceedings · doi:10.4065/83.10.1146 · Cited by 121 · see citing works
Hurria, A., Browner, I. S., Cohen, H. J., Denlinger, C. S., deShazo, M., Extermann, M., Ganti, A. K., Holland, J. C., Holmes, H. M., Karlekar, M. B., et al. (2012) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2012.0019 · Cited by 114 · see citing works
Self-citationImmune system and sarcopenia: Presented relationship and future perspective
Zhang, X., Li, H., He, M., Wang, J., Wu, Y., & Li, Y. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111823 · Cited by 112 · see citing works
Interventions for Human Frailty: Physical Activity as a ModelPreprint
Fried, L. P. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a025916 · Cited by 110 · see citing works
“, interleukin 6 [IL-6] and C-reactive protein [CRP]) with aging (Ershler and Keller 2000; Reuben et al. 2002; Cohen et al. 2003; Joseph et al. 2005).”
BackgroundRichner, J. M., Gmyrek, G. B., Govero, J., Tu, Y., van der Windt, G. J. W., Metcalf, T. U., Haddad, E. K., Textor, J. C., Miller, M. J., & Diamond, M. S. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005027 · Cited by 109 · see citing works
“Levels of cytokines (IL-1α (A), IL-1β (B), IL-2 (C), IL-6 (D), IL-10 (E), IL12 p40 (F), IL-17, (G), and IFN-γ (H)) and chemokines (MCP-1 (I), MIP-1α (J), MIP-1β (K), and RANTES (L)) in DLN were measured by Bio-Plex assay.”
BackgroundBaker, J. V., Ayenew, W., Quick, H. S., Hullsiek, K. H., Tracy, R. P., Henry, K., Duprez, D. A., & Neaton, J. D. (2009) · The Journal of Infectious Diseases · doi:10.1086/649560 · Cited by 111 · see citing works
Inflammation and Thrombosis Biomarkers and Incident Frailty in Postmenopausal Women
Reiner, A. P., Aragaki, A. K., Gray, S. L., Wactawski‐Wende, J., Cauley, J. A., Cochrane, B. B., Kooperberg, C. L., Woods, N. F., & LaCroix, A. Z. (2009) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.04.016 · Cited by 108 · see citing works
“otal white blood count, and circulating T-lymphocytes exressing C-C chemokine receptor-5.(4-10) In an experimental ouse model of proinflammatory pathway activation due to eficiency of the anti-inflammatory cytokine IL-10, muscle eakness and higher IL-6 levels developed more rapily with increasing age compared ith cont…”
High, K. P., Bradley, S., Loeb, M. B., Palmer, R. M., Quagliarello, V., & Yoshikawa, T. T. (2004) · Clinical Infectious Diseases · doi:10.1086/426082 · Cited by 106 · see citing works
“IGF-1 strongly enhances both muscle regeneration [52, 53] and muscle contractility via excitation-contraction coupling [40], but IGF-1 expression and activity are blunted by inflammation.”
BackgroundBacteremia and Sepsis in Older Adults
Girard, T. D., & Ely, E. W. (2007) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2007.05.003 · Cited by 107 · see citing works
“A prothrombotic state, which contributes to the increased risk of sepsis and death in infected patients, exists in older persons, as evidenced by increased concentrations of D-dimer, activated factor VII, and other coagulation factors [26,27].”
BackgroundHsu, D. C., & Sereti, I. (2016) · Drugs · doi:10.1007/s40265-016-0546-7 · Cited by 102 · see citing works
Measuring Systemic Inflammatory Regulation in Older Adults: Evidence and Utility
Bandeen-Roche, K., Walston, J. D., Huang, Y., Semba, R. D., & Ferrucci, L. (2009) · Rejuvenation Research · doi:10.1089/rej.2009.0883 · Cited by 94 · see citing works
Ledwaba, L., Tavel, J. A., Khabo, P., Maja, P., Qin, J., Sangweni, P., Liu, X., Follmann, D. A., Metcalf, J. A., Orsega, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0024243 · Cited by 99 · see citing works
Underlying Disorders and Their Impact on the Host Response to Infection
Dhainaut, J.-F., Claessens, Y.-É., Janes, J., & Nelson, D. R. (2005) · Clinical Infectious Diseases · doi:10.1086/432001 · Cited by 97 · see citing works
“[42] reported that activation of the coagulation (d-dimer) and inflammatory (IL-6) pathways at”
BackgroundPersistent Infection, Inflammation, and Functional Impairment in Older Latinos
Aiello, A. E., Haan, M. N., Pierce, C. M., Simanek, A. M., & Liang, J. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.6.610 · Cited by 96 · see citing works
Frailty and Risk of Venous Thromboembolism in Older Adults
Folsom, A. R., Boland, L. L., Cushman, M., Heckbert, S. R., Rosamond, W. D., & Walston, J. D. (2007) · The Journals of Gerontology Series A · doi:10.1093/gerona/62.1.79 · Cited by 96 · see citing works
“Recent evidence has linked frailty with activation of the inflammatory and coagulation systems (7), and this activation may be associated with subsequent decline in function and mortality in elderly persons (8).”
Zaslavsky, O., Cochrane, B. B., Thompson, H. J., Woods, N. F., Herting, J. R., & LaCroix, A. Z. (2012) · Biological Research For Nursing · doi:10.1177/1099800412462866 · Cited by 94 · see citing works
Balage, M., Avérous, J., Rémond, D., Bos, C., Pujos‐Guillot, E., Papet, I., Mosoni, L., Combaret, L., & Dardevet, D. P. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2009.01.005 · Cited by 92 · see citing works
Immunological outcomes of exercise in older adults
Senchina, D. S., & Kohut, M. L. (2007) · Clinical Interventions in Aging · doi:10.2147/ciia.2007.2.1.3 · Cited by 91 · see citing works
Preliminary Evidence for Subdimensions of Geriatric Frailty: The MacArthur Study of Successful Aging
Sarkisian, C. A., Gruenewald, T. L., Boscardin, W. J., & Seeman, T. E. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.02041.x · Cited by 92 · see citing works
Senior Adult Oncology Clinical Practice Guidelines in Oncology
Balducci, L., Cohen, H. J., Engstrom, P. F., Ettinger, D. S., Halter, J. B., Gordon, L. I., Kiel, K. D., Kneier, A., Lim, D. W., Petersdorf, S. H., et al. (2005) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2005.0032 · Cited by 92 · see citing works
Self-citationPhysical Activity, Sedentary Behavior, and Inflammatory and Hemostatic Markers in Men
Parsons, T. J., Sartini, C., Welsh, P. I., Sattar, N. A., Ash, S., LENNON, L. T., Wannamethee, S. G., Lee, I.-M. M., Whincup, P. H., & Jefferis, B. J. M. H. (2016) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001113 · Cited by 91 · see citing works
“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
Ely, E. W., Angus, D. C., Williams, M. D., Bates, B. M., Qualy, R. L., & Bernard, G. R. (2003) · Clinical Infectious Diseases · doi:10.1086/375775 · Cited by 91 · see citing works
“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].”
BackgroundBalducci, L. (2003) · PubMed · Cited by 88 · see citing works
Rousseau, J. H., Kleppinger, A., & Kenny, A. M. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.01870.x · Cited by 88 · see citing works
“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 · see citing works
“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).”
BackgroundPallis, A. G., Hatse, S., Brouwers, B. A. H., Pawelec, G., Falandry, C., Wedding, U., Lago, L. D., Repetto, L., Ring, A. E., & Wildiers, H. P. M. W. (2013) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2013.09.001 · Cited by 84 · see citing works
“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
Lichtfuss, G. F., Hoy, J., Rajasuriar, R., Kramski, M., Crowe, S. M., & Lewin, S. R. (2011) · Biomarkers in Medicine · doi:10.2217/bmm.11.15 · Cited by 83 · see citing works
Wu, I., Lin, C., & Hsiung, C. A. (2015) · Biomedicine · doi:10.7603/s40681-015-0001-1 · Cited by 82 · see citing works
“[94] IL-6, D-dimer Longitudinal study (5 y) 1723 men and women aged 72 y Mortality and disability High levels of IL-6 and D-dimer predicted death and disability T1”
BackgroundPlasma Hypertonicity: Another Marker of Frailty?
Stookey, J. D., Purser, J. L., Pieper, C. F., & Cohen, H. J. (2004) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2004.52361.x · Cited by 80 · see citing works
“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
Goyette, R. E., Key, N. S., & Ely, E. W. (2004) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-2004-860979 · Cited by 81 · see citing works
“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 · see citing works
Anemia in the elderly—Clinical findings and impact on health
Balducci, L., Ershler, W. B., & Krantz, S. B. (2006) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.09.003 · Cited by 76 · see citing works
Incorporating Biomarkers Into Cancer and Aging Research
Hubbard, J. M., Cohen, H. J., & Muss, H. B. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2014.55.4261 · Cited by 76 · see citing works
“increased chronic inflammatory and procoagulant markers predict functional decline.(15-19,45,46) In an analysis of moderately to severely”
BackgroundSelf-citationLi, H., Liu, W., & Xie, J. (2017) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2017.08.007 · Cited by 76 · see citing works
The frail renin–angiotensin system
Abadir, P. M. (2011) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2010.08.004 · Cited by 70 · see citing works
Cardiovascular implications from untreated human immunodeficiency virus infection
Baker, J. V., & Lundgren, J. D. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehq483 · Cited by 75 · see citing works
“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
Muss, H. B., Biganzoli, L., Sargent, D. J., & Aapro, M. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.10.3457 · Cited by 75 · see citing works
Inflammation and mortality in a frail mouse model
Ko, F., Yu, Q., Xue, Q., Yao, W., Brayton, C. F., Yang, H., Fedarko, N. S., & Walston, J. D. (2011) · AGE · doi:10.1007/s11357-011-9269-6 · Cited by 74 · see citing works
Presepsin (sCD14-ST) in emergency department: The need for adapted threshold values?
Chenevier‐Gobeaux, C., Trabattoni, E., Roelens, M., Borderie, D., & Claessens, Y.-É. (2013) · Clinica Chimica Acta · doi:10.1016/j.cca.2013.09.019 · Cited by 74 · see citing works
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 74 · see citing works
“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.”
BackgroundRønning, B., Wyller, T. B., Seljeflot, I., Slaaen, M., Skovlund, E., Nesbakken, A., & Rostoft, S. (2010) · Age and Ageing · doi:10.1093/ageing/afq123 · Cited by 74 · see citing works
“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 73 · see citing works
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 · see citing works
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 · see citing works
Self-citation
- 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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