The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
The Pathophysiologic Roles of Interleukin-6 in Human Disease
Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., & Chrousos, G. P. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-2-199801150-00009 · Cited by 1,146
Relation of C-Reactive Protein and Coronary Heart Disease in the MRFIT Nested Case-Control Study
Kuller, L. H., Tracy, R. P., Shaten, J., & Meilahn, E. N. (1996) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a008963 · Cited by 1,098
Self-citationMendall, M. A., Patel, P., Ballam, L., Strachan, D. P., & Northfield, T. C. (1996) · BMJ · doi:10.1136/bmj.312.7038.1061 · Cited by 851
C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor
Čermák, J., Key, N., Bach, R., Balla, J., Jacob, H., & Vercellotti, G. (1993) · Blood · doi:10.1182/blood.v82.2.513.513 · Cited by 838
Tracy, R. P., Lemaitre, R. N., Psaty, B. M., Ives, D. G., Evans, R. W., Cushman, M., Meilahn, E. N., & Kuller, L. H. (1997) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.17.6.1121 · Cited by 836
Self-citationMacy, E. M., Hayes, T. E., & Tracy, R. P. (1997) · Clinical Chemistry · doi:10.1093/clinchem/43.1.52 · Cited by 797
Self-citationIL-6 and APPs: anti-inflammatory and immunosuppressive mediators.
Tilg, H., Dinarello, C., & Mier, J. (1997) · Immunology today (Amsterdam. Regular ed.) · doi:10.1016/s0167-5699(97)01103-1 · Cited by 687
Davies, M. (1979) · Cited by 605
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
Self-citationThe 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
Self-citationvan der Poll, T., Levi, M. M., Hack, C. E., Cate, H. T., van Deventer, S. J. H., Eerenberg, A. J. M., de Groot, E. R., Jansen, J., Gallati, H., & Buller, H. R. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.4.1253 · Cited by 383
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
Self-citationInfection, inflammation, and infarction: does acute endothelial dysfunction provide a link?
Vallance, P. J., Collier, J., & Bhagat, K. (1997) · The Lancet · doi:10.1016/s0140-6736(96)09424-x · Cited by 308
DeRijk, R. H., Michelson, D., Karp, B., Petrides, J. S., Galliven, E., Deuster, P., Paciotti, G. F., Gold, P. W., & Sternberg, E. M. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.7.4041 · Cited by 250
C‐reactive protein levels as a direct indicator of interleukin‐6 levels in humans in vivo
Bataille, R., & Klein, B. (1992) · Arthritis & Rheumatism · doi:10.1002/art.1780350824 · Cited by 160
Pelliniemi, T., Irjala, K. M. A., Mattila, K. J., Pulkki, K. J., Rajamäki, A., Tienhaara, A., Laakso, M., & Lahtinen, R. (1995) · Blood · doi:10.1182/blood.v85.3.765.bloodjournal853765 · Cited by 133
Lu, Z., Brailly, H., Wijdenes, J., Bataille, R., Rossi, J., & Klein, B. (1995) · Blood · doi:10.1182/blood.v86.8.3123.3123 · Cited by 119
Pannen, B. H. J., & Robotham, J. L. (1995) · PubMed · Cited by 115
Established Populations for Epidemiologic Studies of the Elderly
de Leon, C. F. M. (2012) · doi:10.4135/9781412956208.n79 · Cited by 115
Gauldie, J., Richards, C. D., Northemann, W., Fey, G. H., & Baumann, H. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb23998.x · Cited by 111
Gauldie, J., Richards, C. D., Northemann, W., et al. (1989) · PubMed · Cited by 100
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
Self-citationReactive oxygen intermediates as second messengers of a general pathogen response.
Pa, B., Ra, R., & Hl, P. (1996) · PubMed · Cited by 95
Chronic infections and coronary heart disease
Ånestad, G., Scheel, O., & Hungnes, O. (1997) · The Lancet · doi:10.1016/s0140-6736(97)26040-x · Cited by 74
Mestries, J. C., Kruithof, E. K. O., Gascon, M.-P., Hérodin, F., Agay, D., & Ythier, A. (1994) · PubMed · Cited by 73
Kushner, I., JIANG, S., ZHANG, D., Lozanski, G., & Samols, D. R. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb32318.x · Cited by 62
Geffken, D. F., Fg, K., Mh, K., Es, C., BOVILL, E. G., & Tracy, R. P. (1994) · PubMed · Cited by 58
Self-citationvan Zaanen, H. C. T., Koopmans, R. P., Aarden, L. A., Rensink, H. J. A. M., Stouthard, J. M., Warnaar, S. O., Lokhorst, H. M., & van Oers, M. H. J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118932 · Cited by 57
Circadian characteristics of interleukin-6 in blood and urine of clinically healthy men.
Sothern, R. B., Roitman-Johnson, B., Kanabrocki, E. L., Yager, J. G., Fuerstenberg, R. K., Weatherbee, J. A., Young, M., Nemchausky, B. M., & Scheving, L. E. (1995) · PubMed · Cited by 44
Research works printed but not linked: 1
- Geffken, 1994, The measurement of fibrinogen in population-based research, Arch Pathol Lab Med, 118, 1106
Cited by
Sorted by citations
Clegg, A., Young, J., Iliffe, S., Rikkert, M. O., & Rockwood, K. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62167-9 · Cited by 9,503
Inflammation and Atherosclerosis
Libby, P., Ridker, P. M., & Maseri, A. (2002) · Circulation · doi:10.1161/hc0902.104353 · Cited by 7,724
Pearson, T. A., Mensah, G. A., Alexander, R. W., Anderson, J. L., Cannon, R. O., Criqui, M., Fadl, Y. Y., Fortmann, S. P., Hong, Y., Myers, G. L., et al. (2003) · Circulation · doi:10.1161/01.cir.0000052939.59093.45 · Cited by 6,401
Self-citationRidker, P. M., Hennekens, C. H., Buring, J. E., & Rifai, N. (2000) · New England Journal of Medicine · doi:10.1056/nejm200003233421202 · Cited by 5,850
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
