title: Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Raymond and Anna Lublin Professor of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Rm. 1A.62, Baltimore, MD 21224. jwalston@jhmi.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Varadhan
authors.forename: Wenliang
authors.initials: W
authors.lastname: Yao
authors.forename: Amy
authors.initials: A
authors.lastname: Matteini
authors.forename: Brock A
authors.initials: BA
authors.lastname: Beamer
authors.forename: Qian-Li
authors.initials: QL
authors.lastname: Xue
authors.forename: Huanle
authors.initials: H
authors.lastname: Yang
authors.forename: Bhavish
authors.initials: B
authors.lastname: Manwani
authors.forename: Alexander
authors.initials: A
authors.lastname: Reiner
authors.forename: Nancy
authors.initials: N
authors.lastname: Jenny
authors.forename: Neel
authors.initials: N
authors.lastname: Parekh
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Anne
authors.initials: A
authors.lastname: Newman
authors.forename: Karen
authors.initials: K
authors.lastname: Bandeen-Roche
authors.forename: Russell
authors.initials: R
authors.lastname: Tracy
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Jeremy
authors.initials: J
authors.lastname: Walston
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000401:mortality; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D008136:Longevity / Q000502:physiology*; D008297:Male; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D002097:C-Reactive Protein
keywords: Aging.; Cytokine; Inflammation; Mortality