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

TitleMidlife Systemic Inflammation Is Associated With Frailty in Later Life: The ARIC Study.
Publication TypeJournal Article
Year of Publication2019
AuthorsWalker KA, Walston J, Gottesman RF, Kucharska-Newton AMaria, Palta P
Secondary AuthorsB Windham G
JournalJ Gerontol A Biol Sci Med Sci
Volume74
Issue3
Pagination343-349
Date Published2019 02 15
ISSN1758-535X
KeywordsAged, Biomarkers, C-Reactive Protein, Factor VIII, Female, Fibrinogen, Frailty, Humans, Inflammation, Leukocyte Count, Male, Middle Aged, Risk Factors, von Willebrand Factor
Abstract

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

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

DOI10.1093/gerona/gly045
Alternate JournalJ Gerontol A Biol Sci Med Sci
PubMed ID29534173
PubMed Central IDPMC6376088
Grant ListU01 HL096812 / HL / NHLBI NIH HHS / United States
T32 AG027668 / AG / NIA NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
P30 AG021334 / AG / NIA NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
K24 AG052573 / AG / NIA NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
R01 AG050560 / AG / NIA NIH HHS / United States
K99 AG052830 / AG / NIA NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States