Title | Midlife Systemic Inflammation Is Associated With Frailty in Later Life: The ARIC Study. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Walker KA, Walston J, Gottesman RF, Kucharska-Newton AMaria, Palta P |
Secondary Authors | B Windham G |
Journal | J Gerontol A Biol Sci Med Sci |
Volume | 74 |
Issue | 3 |
Pagination | 343-349 |
Date Published | 2019 02 15 |
ISSN | 1758-535X |
Keywords | Aged, 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. |
DOI | 10.1093/gerona/gly045 |
Alternate Journal | J Gerontol A Biol Sci Med Sci |
PubMed ID | 29534173 |
PubMed Central ID | PMC6376088 |
Grant List | U01 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 |