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J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):343-349. doi: 10.1093/gerona/gly045.

Midlife Systemic Inflammation Is Associated With Frailty in Later Life: The ARIC Study.

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Department of Neurology, Center on Aging and Health, Baltimore, MD.
Division of Geriatric Medicine and Gerontology, Center on Aging and Health, Baltimore, MD.
Department of Epidemiology, Johns Hopkins University, Baltimore, MD.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill.
Department of Medicine, Division of Geriatrics, University of Mississippi Medical Center, Jackson.



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.


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.


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).


Systemic inflammation during midlife may independently promote pathophysiological changes underlying frailty in a subset of the population.


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

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