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Cited by 1,488Adipokines, Inflammation, and Metabolic DiseasesInflammatory Biomarkers in Disease PrognosisLipoproteins and Cardiovascular Health

Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly

Harris, Tamara B, Ferrucci, Luigi, Tracy, Russell P, Corti, M.Chiara, Wacholder, Sholom, Ettinger, Walter H, Heimovitz, Harley, Cohen, Harvey J +1 more·1999·The American Journal of Medicine
DOI 10.1016/s0002-9343(99)00066-2
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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 IL-6 values >3.19 pg/ml.

    “Epidemiological studies of individuals 65 or older have found that the highest quartile had values &gt; 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]

  • Participants in the upper quartile of IL-6 had a 2-fold greater risk of death compared with the lowest quartile.

    “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]

  • Inflammation appears central to frailty via an abnormal low-grade state that overreacts to stimuli and remains active long after the trigger is gone.

    “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]

  • Only high-molecular-weight serum fractions from diabetic nephropathy patients stimulate RAGE, and supramolecular complexes are a prerequisite for RAGE binding.

    “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]

  • 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.

    “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]

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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
ORCID
Venue
The American Journal of Medicine
Publisher
Elsevier BV
Published
1999-05
Volume
106
Issue
5
Pages
506-512
ISSN
0002-9343 (ISSN-L)
DOI
10.1016/s0002-9343(99)00066-2
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
Licence
Locations
  • The American Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG02106)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
  • Health Sciences › Medicine › Surgery › 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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