Midlife systemic inflammation is associated with frailty in later life: The ARIC study

Keenan A. Walker, Jeremy Walston, Rebecca F. Gottesman, Anna Kucharska-Newton, Priya Palta, B. Gwen Windham

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background: Evidence suggests that systemic inflammation may have a mechanistic role in age-related frailty, yet prospective data is limited. We examined whether systemic inflammation during midlife was associated with late-life frailty within the community-based Atherosclerosis Risk in Communities Study. Methods: Plasma levels of four inflammatory markers (fibrinogen, von Willebrand factor, and Factor VIII, and white blood cell count) were measured during Visit 1 (1987-1989; mean age: 52 [5]), standardized into z-scores, and combined to create an inflammation composite score. High-sensitivity C-reactive protein (CRP) was measured 3 (Visit 2, 1990-1992) and 9 (Visit 4, 1996-1999) years later. Frailty was evaluated in 5,760 participants during late life (Visit 5, 2011-2013; mean age: 75 [5]). Analyses were adjusted for demographic and physiological variables, and midlife medical comorbidity using logistic regression. Results: A 1 SD increase in midlife inflammation composite score was associated with higher odds of frailty 24 years later (odds ratio [OR] = 1.39, 95% confidence interval [CI]: 1.18-1.65). Similarly, each standard deviation increase in Visit 2 CRP (OR = 1.24, 95% CI: 1.09-1.40) and Visit 4 CRP (OR = 1.35, 95% CI: 1.19-1.53) was associated with a higher odds of frailty 21 and 15 years later. Participants who maintained elevated CRP (≥3 mg/L) at Visits 2 and 4 or transitioned to a state of elevated CRP during this period were more likely to subsequently meet frailty criteria compared to those who maintained low CRP. These associations were stronger among white, compared to African American, participants (p-interactions <.038). Conclusions: Systemic inflammation during midlife may independently promote pathophysiological changes underlying frailty in a subset of the population.

Original languageEnglish
Pages (from-to)343-349
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number3
StatePublished - Feb 15 2019

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (grant numbers HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This study was also supported by contracts from the National Institute on Aging (T32 AG027668 to K.A.W., K99-AG052830 to P.P., K24 AG052573 to R.F.G., and P30AG021334 and R01AG050560 to J.W.).

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.


  • Acute-phase proteins
  • C-reactive protein
  • Cohort study
  • Immune system
  • Risk factor

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


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