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Associations of elevated Interleukin-6 and C-Reactive protein levels with mortality in the elderly
Abstract
Purpose To investigate whether interleukin-6 and C-reactive protein levels predict all-cause and cause-specific mortality in a population-based sample of nondisabled older people.Subjects and methods A sample of 1,293 healthy, nondisabled participants in the Iowa 65+ Rural Health Study was followed prospectively for a mean of 4.6 years. Plasma interleukin-6 and C-reactive protein levels were measured in specimens obtained from 1987 to 1989.Results Higher interleukin-6 levels were associated with a twofold greater risk of death [relative risk (RR) for the highest quartile (> or = 3.19 pg/mL) compared with the lowest quartile of 1.9 [95% confidence interval, CI, 1.2 to 3.1]). Higher C-reactive protein levels (> or = 2.78 mg/L) were also associated with increased risk (RR = 1.6; CI, 1.0 to 2.6). Subjects with elevation of both interleukin-6 and C-reactive protein levels were 2.6 times more likely (CI, 1.6 to 4.3) to die during follow-up than those with low levels of both measurements. Similar results were found for cardiovascular and noncardiovascular causes of death, as well as when subjects were stratified by sex, smoking status, and prior cardiovascular disease, and for both early (<2.3 years) and later follow-up. Results were independent of age, sex, body mass index, and history of smoking, diabetes, and cardiovascular disease, as well as known indicators of inflammation including fibrinogen and albumin levels and white blood cell count.Conclusions Higher circulating levels of interleukin-6 and C-reactive protein were associated with mortality in this population-based sample of healthy older persons. These measures may be useful for identification of high-risk subgroups for anti-inflammatory interventions.
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“Epidemiological studies of individuals 65 or older have found that the highest quartile had values > 3.19 pg ∕ ml (39, 40).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [39]
In the citing paper
“As one illustration of risk, participants in the upper quartile had a 2-fold greater risk of death compared with the lowest quartile (39).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [39]
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“There is evidence that inflammation has a key role in the pathophysiology of frailty through an abnormal, low-grade inflammatory response that is hyper-responsive to stimuli and that persists for a prolonged period following removal of the initial inflammatory stimulus (19, 52-57).”
From Frailty in elderly people (2013) · cites this paper as [53]
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“Penfold et al. (535) recently showed that only serum fractions isolated from diabetic patients with nephropathy containing high-molecular-weight proteins (. 50 kD) were able to stimulate RAGE but not medium-or low-molecular-weight serum fractions, in line with mechanistic studies that showed no binding of carboxymethyllysine-modified proteins to RAGE (536 -538) , and that supramolecular complexes”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [536]
In the citing paper
“IL-6 is associated with chronic stress, a number of chronic diseases, and negative health behaviors, and is a major predictor of mortality in older persons [67, 68].”
From Personality and Longevity: Knowns, Unknowns, and Implications for Public Health and Personalized Medicine (2011) · cites this paper as [67]
Citations
Cites
Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P., & Hennekens, C. H. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704033361401 · Cited by 5,504
Self-citationThe Prognostic Value of C-Reactive Protein and Serum Amyloid A Protein in Severe Unstable Angina
Liuzzo, G., Biasucci, L. M., Gallimore, J. R., Grillo, R. L., Rebuzzi, A. G., Pepys, M. B., & Maseri, A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199408183310701 · Cited by 2,354
Thompson, S. G., Kienast, J., Pyke, S., Haverkate, F., & van de Loo, J. C. W. (1995) · New England Journal of Medicine · doi:10.1056/nejm199503093321003 · Cited by 1,819
Moreland, L. W., Baumgartner, S. W., Schiff, M. H., Tindall, E. A., Fleischmann, R., Weaver, A. L., Ettlinger, R. E., Cohen, S. B., Koopman, W. J., Mohler, K. M., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707173370301 · Cited by 1,620
Xing, Z., Gauldie, J., Cox, G., Baumann, H., Jordana, M., Lei, X.-F., & Achong, M. K. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1368 · Cited by 1,578
Production of C-reactive protein and risk of coronary events in stable and unstable angina
Haverkate, E., Thompson, S. G., Pyke, S., Gallimore, J. R., & Mark B Pepys Group (1997) · The Lancet · doi:10.1016/s0140-6736(96)07591-5 · Cited by 1,511
A Case-Cohort Design for Epidemiologic Cohort Studies and Disease Prevention Trials
Prentice, R. L. (1986) · Biometrika · doi:10.1093/biomet/73.1.1 · Cited by 1,444
Increased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6
Jilka, R. L., Hangoc, G., Girasole, G., Passeri, G., Williams, D. C., Abrams, J. S., Boyce, B. F., Broxmeyer, H. E., & Manolagas, S. C. (1992) · Science · doi:10.1126/science.1621100 · Cited by 1,440
Chronic infections and coronary heart disease: is there a link?
Danesh, J., Collins, R., & Peto, R. (1997) · The Lancet · doi:10.1016/s0140-6736(97)03079-1 · Cited by 1,333
Torre-Amione, G., Kapadia, S., Benedict, C., Oral, H., Young, J. B., & Mann, D. L. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00589-7 · Cited by 1,211
Research works printed but not linked: 1
- Geffken, 1994, The measurement of fibrinogen in population-based research, Arch Pathol Lab Med, 118, 1106
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Vine, A. K., Stader, J., Branham, K., Musch, D. C., & Swaroop, A. (2005) · Ophthalmology · doi:10.1016/j.ophtha.2005.07.004 · Cited by 160
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Franceschi, C., Valensin, S., Fagnoni, F., Barbi, C., & Bonafè, M. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00068-6 · Cited by 154
Dardevet, D., Rémond, D., Peyron, M.-A., Papet, I., Savary-Auzeloux, I., & Mosoni, L. (2012) · The Scientific World JOURNAL · doi:10.1100/2012/269531 · Cited by 153
Giuliani, N., Sansoni, P., Girasole, G., Vescovini, R., Passeri, G., Passeri, M., & Pedrazzoni, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00220-5 · Cited by 151
Nikkheslat, N., Zunszain, P. A., Horowitz, M. A., Barbosa, I. G., Parker, J. A., Myint, A.-M., Schwarz, M. J., Tylee, A. T., Carvalho, L. A., & Pariante, C. M. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.02.002 · Cited by 147
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Bruunsgaard, H., Bjerregaard, E., Schroll, M., & Pedersen, B. K. (2004) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2004.52061.x · Cited by 109
Associations of high sensitivity C-reactive protein levels in schizophrenia and comparison groups
Joseph, J., Depp, C., Martin, A. S., Daly, R. E., Glorioso, D. K., Palmer, B. W., & Jeste, D. V. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.08.019 · Cited by 109
Long-Term Physical Activity and Inflammatory Biomarkers in Older Adults
BEAVERS, K. M., HSU, F.-C., ISOM, S., KRITCHEVSKY, S. B., CHURCH, T., GOODPASTER, B., PAHOR, M., & NICKLAS, B. J. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181e3ac80 · Cited by 108
Gender, race/ethnicity, personality, and interleukin-6 in urban primary care patients
Chapman, B. P., Khan, A., Harper, M., Stockman, D., Fiscella, K., Walton, J., Duberstein, P., Talbot, N., Lyness, J. M., & Moynihan, J. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.12.009 · Cited by 103
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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
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Effects of exercise on the immune system in the elderly population
Bruunsgaard, H., & Pedersen, B. K. (2000) · Immunology & Cell Biology · doi:10.1111/j.1440-1711.2000.t01-14-.x · Cited by 95
Can blocking inflammation enhance immunity during aging?
Chambers, E. S., & Akbar, A. N. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.016 · Cited by 92
Leng, S., Xue, Q.-L., Huang, Y., Semba, R., Chaves, P., Bandeen-Roche, K., Fried, L., & Walston, J. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.2.195 · Cited by 86
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Reuben, D. B., Ferrucc, L., Wallace, R., Tracy, R. P., Corti, M. C., Heimovitz, H., & Harris, T. B. (2000) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2000.tb02629.x · Cited by 66
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Palella, F. J., Gange, S. J., Benning, L., Jacobson, L., Kaplan, R. C., Landay, A. L., Tracy, R. P., & Elion, R. (2010) · AIDS · doi:10.1097/qad.0b013e3283389dfa · Cited by 61
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Denollet, J., Vrints, C. J., & Conraads, V. M. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.10.015 · Cited by 58
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Saini, A., Sharples, A. P., Al-Shanti, N., & Stewart, C. E. (2017) · Biogerontology · doi:10.1007/s10522-016-9667-3 · Cited by 53
Sleep Disturbance and Older Adults' Inflammatory Responses to Acute Stress
Heffner, K. L., Ng, H. M., Suhr, J. A., France, C. R., Marshall, G. D., Pigeon, W. R., & Moynihan, J. A. (2012) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31824361de · Cited by 52
The inflammatory response to social defeat is increased in older mice
Kinsey, S. G., Bailey, M. T., Sheridan, J. F., & Padgett, D. A. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.003 · Cited by 48
Zampino, M., Brennan, N. A., Kuo, P.-L., Spencer, R. G., Fishbein, K. W., Simonsick, E. M., & Ferrucci, L. (2020) · GeroScience · doi:10.1007/s11357-020-00208-x · Cited by 43
Self-citationDeverts, D. J., Cohen, S., Kalra, P., & Matthews, K. A. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.07.017 · Cited by 44
Smith, B. W., Shelley, B. M., Sloan, A. L., Colleran, K., & Erickson, K. (2018) · Mindfulness · doi:10.1007/s12671-017-0824-9 · Cited by 37
Elliot, A. J., Turiano, N. A., & Chapman, B. P. (2017) · Annals of Behavioral Medicine · doi:10.1007/s12160-016-9847-z · Cited by 37
“Biomarkers of systemic inflammation, including interleukin-6 (IL-6) and C-reactive protein (CRP), are key indicators of disease risk in middle age and older adulthood as they are prospectively associated with coronary heart disease [17, 18] as well as diabetes [19], disability [20], and all-cause mortality [21].”
BackgroundTomfohr, L. M., Edwards, K. M., Madsen, J. W., & Mills, P. J. (2015) · Psychophysiology · doi:10.1111/psyp.12549 · Cited by 33
Luukinen, H., Jokelainen, J., & Hedberg, P. (2010) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365510903410548 · Cited by 25
Haider, S., Grabovac, I., Winzer, E., Kapan, A., Schindler, K. E., Lackinger, C., Titze, S., & Dorner, T. E. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185879 · Cited by 24
Leite, M. M., Dutra, M. T., da Costa, M. V. G., Funghetto, S. S., Silva, A. D. O., de Lima, L. R., da Silva, I. C. R., Mota, M. R., & Stival, M. M. (2021) · Experimental Gerontology · doi:10.1016/j.exger.2021.111389 · Cited by 15
New Clinical Markers Predictive of Cardiovascular Disease: The Role of Inflammatory Mediators
Rackley, C. E. (2004) · Cardiology in Review · doi:10.1097/01.crd.0000126083.86717.5b · Cited by 14
Inflammation Through a Psychoneuroimmunological Lens
Bennett, J. M., Gillie, B. L., Lindgren, M. E., Fagundes, C. P., & Kiecolt-Glaser, J. K. (2013) · Handbook of Systems and Complexity in Health · doi:10.1007/978-1-4614-4998-0_19 · Cited by 15
Metadata
- Authors
- Harris, T. B., Ferrucci, L., Tracy, R. P., Corti, M. C., Wacholder, S., Ettinger, W. H., Heimovitz, H., Cohen, H. J., & Wallace, R.
- Affiliations
- National Institutes of Health (US)
- University of Vermont (US)
- University of Padua (IT)
- National Cancer Institute (US)
- Atrium Health Wake Forest Baptist (US)
- Duke University (US)
- University of Iowa (US)
- Corresponding author
- Harris, Tamara B
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 106
- Issue
- 5
- Pages
- 506-512
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2054893928
- Cited by
- 1,488
- References
- 39
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 29 · 2023: 27 · 2022: 34 · 2021: 42 · 2020: 38 · 2019: 46 · 2018: 47 · 2017: 48 · 2016: 63 · 2015: 64 · 2014: 72 · 2013: 67 · 2012: 75
- FWCI
- 38.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG02106)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- interleukin-6, C-reactive protein, mortality, older adults, inflammation, cardiovascular mortality, all-cause mortality, prognostic factors, anti-inflammatory therapy
- MeSH terms
- Aged, C-Reactive Protein, Cause of Death, Female, Humans, Inflammation, Iowa, Male, Mortality, Predictive Value of Tests, Prospective Studies, Risk, Rural Health, Biomarkers, Interleukin-6
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