TitleChronic inflammation as a determinant of future aging phenotypes.
Publication TypeJournal Article
Year of Publication2013
AuthorsAkbaraly, TN, Hamer, M, Ferrie, JE, Lowe, G, Batty, GD, Hagger-Johnson, G, Singh-Manoux, A, Shipley, MJ, Kivimäki, M
JournalCMAJ
Volume185
Issue16
PaginationE763-70
Date Published2013 Nov 05
ISSN1488-2329
KeywordsAging, Cardiovascular Diseases, Chronic Disease, Female, Follow-Up Studies, Humans, Inflammation, Interleukin-6, Male, Middle Aged, Odds Ratio, Phenotype
Abstract

BACKGROUND: The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women.

METHODS: We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study's baseline (1997-1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007-2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants).

RESULTS: Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38-0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15-2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58-3.80).

INTERPRETATION: Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.

DOI10.1503/cmaj.122072
Alternate JournalCMAJ
PubMed ID24043651
PubMed Central IDPMC3826354
Grant List / / British Heart Foundation / United Kingdom
RG/13/2/30098 / / British Heart Foundation / United Kingdom
R01 HL036310 / HL / NHLBI NIH HHS / United States
K013351 / / Medical Research Council / United Kingdom
/ / Department of Health / United Kingdom
R01 AG034454 / AG / NIA NIH HHS / United States
MR/K013351/1 / / Medical Research Council / United Kingdom
R01 AG013196 / AG / NIA NIH HHS / United States
PG/11/63/29011 / / British Heart Foundation / United Kingdom
HS06516 / HS / AHRQ HHS / United States
R01AG034454 / AG / NIA NIH HHS / United States
R01HL036310 / HL / NHLBI NIH HHS / United States
R01AG013196 / AG / NIA NIH HHS / United States