Cited by 279Inflammatory Biomarkers in Disease PrognosisAdipokines, Inflammation, and Metabolic DiseasesSepsis Diagnosis and Treatment

Simple Biologically Informed Inflammatory Index of Two Serum Cytokines Predicts 10 Year All-Cause Mortality in Older Adults

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Varadhan, R., Yao, W., Matteini, A., Beamer, B. A., Xue, Q.-l., Yang, H., Manwani, B., Reiner, A. +8 more·2014·The Journals of Gerontology Series A: Biological Sciences and Medical Sciences

Abstract

BACKGROUND: Individual measurements of inflammation have been utilized to assess adverse outcomes risk in older adults with varying degrees of success. This study was designed to identify biologically informed, aggregate measures of inflammation for optimal risk assessment and to inform further biological study of inflammatory pathways. METHODS: In total, 15 nuclear factor-kappa B-mediated pathway markers of inflammation were first measured in baseline serum samples of 1,155 older participants in the InCHIANTI population. Of these, C-reactive protein, interleukin-1-receptor antagonist, interleukin-6, interleukin-18, and soluble tumor necrosis factor-α receptor-1 were independent predictors of 5-year mortality. These five inflammatory markers were measured in baseline serum samples of 5,600 Cardiovascular Health Study participants. A weighted summary score, the first principal component summary score, and an inflammation index score were developed from these five log-transformed inflammatory markers, and their prediction of 10-year all-cause mortality was evaluated in Cardiovascular Health Study and then validated in InCHIANTI. RESULTS: The inflammation index score that included interleukin-6 and soluble tumor necrosis factor-α receptor-1 was the best predictor of 10-year all-cause mortality in Cardiovascular Health Study, after adjusting for age, sex, education, race, smoking, and body mass index (hazards ratio = 1.62; 95% CI: 1.54, 1.70) compared with all other single and combined measures. The inflammation index score was also the best predictor of mortality in the InCHIANTI validation study (hazards ratio 1.33; 95% CI: 1.17-1.52). Stratification by sex and CVD status further strengthened the association of inflammation index score with mortality. CONCLUSION: A simple additive index of serum interleukin-6 and soluble tumor necrosis factor-α receptor-1 best captures the effect of chronic inflammation on mortality in older adults among the 15 biomarkers measured.

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  • Serum levels of IL-6 and soluble TNFα could be used as an inflammatory index to predict mortality in the elderly.

    “In addition, a separate multistage population-based study reported that serum levels of IL-6 and soluble TNFα could be used as an inflammatory index to predict mortality in the elderly (Varadhan et al, 2014).”

    From Microglia Priming with Aging and Stress (2017) · cites this paper as Varadhan et al, 2014

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  1. Fried LP. The epidemiology of frailty: the scope of the problem. In: Perry HM, Morley JE, Coe RM, eds. Aging, Musculoskeletal Disorders and Care of the Frail Elderly. New York: Springer; 1993:3-16.

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Authors
Varadhan, R., Yao, W., Matteini, A., Beamer, B. A., Xue, Q.-L., Yang, H., Manwani, B., Reiner, A., Jenny, N., Parekh, N., Fallin, M. D., Newman, A., Bandeen-Roche, K., Tracy, R., Ferrucci, L., & Walston, J.
Affiliations
  • Johns Hopkins University (US)
  • Baltimore VA Medical Center (US)
  • University of Washington (US)
  • University of Vermont (US)
  • University of Pittsburgh (US)
  • National Institute on Aging (US)
Venue
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Published
2013-05-20
Volume
69A
Issue
2
Pages
165-173
ISSN
  • 1079-5006 (ISSN-L)
  • 1758-535X
OpenAlex
W2117554687
Cited by
273
References
39
Citations by year
2026: 10 · 2025: 16 · 2024: 27 · 2023: 20 · 2022: 33 · 2021: 23 · 2020: 40 · 2019: 19 · 2018: 22 · 2017: 15 · 2016: 16 · 2015: 23 · 2014: 7 · 2013: 2
FWCI
8.56
Type
journal article
Language
en
Open access
Locations
  • The Journals of Gerontology Series A (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Johns Hopkins University
  • Ministero della Salute (N.1-AG-1-2111, 263 MD 821336, 263 MD 9164, N.1-AG-1-1)
  • National Institutes of Health (263MD9164, N.1-AG-1-2111, N.1-AG-1-1, N01-HC-85239, UL1TR001079, 263 MD 821336, n01hc055222-001, N01HC85086, AG 20098, N01HC85079, AG-023629, N01-HC-75150, N01HC-35129, N01HC-15103, N01-HC-45133, HL080295)
  • National Institute on Aging (N.1‐AG‐1‐2111, 263 MD 9164, N01HC85079, R01AG027236, N01‐HC‐85239, 821336, N01 HC‐15103, AG-023629, AG-15928, AG-20098, and AG-027058, AG 20098, N.1-AG-1-1, AG-15928, 263MD821336, 1-AG-1-2111, N01HC55222, N01‐HC‐35129, N01-HC-75150, AG023629, AG027058, HL080295, N01‐HC‐45133, N01‐HC‐85086, R01AG023629, R01AG015928, R01AG027058, P30AG024827, P30AG021334)
  • National Heart, Lung, and Blood Institute (AG-023629, AG-027058, N0-1-HC-85239, N01HC15103, N01HC‐75150, N01 HC85086, AG-20098, N01 HC55222, N01‐HC‐45133, AG-15928, N01-HC-85079 through N01-HC-85086, HL080295, N01-HC85079, N01HC35129)
  • National Institute of Neurological Disorders and Stroke (AG023629, AG‐15928, AG‐027058, N01-HC-85239, AG‐20098, N01-HC-75150, HL080295, N01-HC-35129, N01-HC-45133, N01-HC-85086, N01 HC-55222, N01HC85079, N01-HC-15103)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Keywords
inflammation, all-cause mortality, older adults, interleukin-6, soluble tumor necrosis factor receptor 1, inflammation index, C-reactive protein, interleukin-1 receptor antagonist, IL-18, chronic inflammation, risk prediction, cardiovascular disease, sex differences, Cardiovascular Health Study
MeSH terms
Aged, Aged, 80 and over, C-Reactive Protein, Female, Humans, Inflammation, Longevity, Male, Risk Factors, Cohort Studies, Biomarkers, Interleukin-6, Interleukin-18, Receptors, Tumor Necrosis Factor, Type I, Interleukin 1 Receptor Antagonist Protein

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