Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: The cardiovascular health study all stars study

Jorge R. Kizer, Alice M. Arnold, Nancy S. Jenny, Mary Cushman, Elsa S. Strotmeyer, Diane G. Ives, Jingzhong Ding, Stephen B. Kritchevsky, Paulo H M Chaves, Calvin H Hirsch, Anne B. Newman

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background. Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.Methods. We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).Results.Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p =. 043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p =. 55), as compared with smaller changes for both.Conclusion. Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.

Original languageEnglish (US)
Pages (from-to)1100-1107
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume66 A
Issue number10
DOIs
StatePublished - Oct 2011

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Adiponectin
Health
C-Reactive Protein
Interleukin-6
Mortality
Anti-Inflammatory Agents
Joints

Keywords

  • Adiponectin
  • Aging
  • C-reactive protein
  • Interleukin 6
  • Mortality

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old : The cardiovascular health study all stars study. / Kizer, Jorge R.; Arnold, Alice M.; Jenny, Nancy S.; Cushman, Mary; Strotmeyer, Elsa S.; Ives, Diane G.; Ding, Jingzhong; Kritchevsky, Stephen B.; Chaves, Paulo H M; Hirsch, Calvin H; Newman, Anne B.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 66 A, No. 10, 10.2011, p. 1100-1107.

Research output: Contribution to journalArticle

Kizer, Jorge R. ; Arnold, Alice M. ; Jenny, Nancy S. ; Cushman, Mary ; Strotmeyer, Elsa S. ; Ives, Diane G. ; Ding, Jingzhong ; Kritchevsky, Stephen B. ; Chaves, Paulo H M ; Hirsch, Calvin H ; Newman, Anne B. / Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old : The cardiovascular health study all stars study. In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2011 ; Vol. 66 A, No. 10. pp. 1100-1107.
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abstract = "Background. Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.Methods. We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).Results.Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95{\%} CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p =. 043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p =. 55), as compared with smaller changes for both.Conclusion. Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.",
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AU - Jenny, Nancy S.

AU - Cushman, Mary

AU - Strotmeyer, Elsa S.

AU - Ives, Diane G.

AU - Ding, Jingzhong

AU - Kritchevsky, Stephen B.

AU - Chaves, Paulo H M

AU - Hirsch, Calvin H

AU - Newman, Anne B.

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N2 - Background. Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.Methods. We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).Results.Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p =. 043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p =. 55), as compared with smaller changes for both.Conclusion. Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.

AB - Background. Adiponectin has anti-inflammatory properties, and its production is suppressed by inflammatory factors. Although elevated levels of adiponectin and inflammatory markers each predict mortality in older adults, the implications of their interdependent actions have not been examined.Methods. We investigated the joint associations of levels and interval changes in adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6) with risk of death in 840 older adults participating in a population-based study. Adiponectin, CRP, and IL-6 were measured in samples collected 8.9 (8.2-9.8) years apart, and all-cause mortality was subsequently ascertained (n = 176).Results.Interval changes and end levels of adiponectin, CRP, and IL-6 showed mostly positive, independent associations with mortality, without evidence of multiplicative interaction. Joint models, however, showed an U-shaped relationship between end level of adiponectin and outcome (hazard ratio [HR] [95% CI] = 0.72 [0.52-0.99] per standard deviation [SD] for levels <20.0 mg/L; HR = 1.91 [1.61-3.44] per SD for levels ≥20.0 mg/L). Participants with the greatest longitudinal increases (upper quartile) in both adiponectin and inflammatory markers had a higher risk of death (HR = 2.85 [1.78-4.58]) than those with large increases in adiponectin alone (HR = 1.87 [1.20-2.92]) (p =. 043), but not inflammatory markers alone (HR = 2.48 [1.67-3.67]) (p =. 55), as compared with smaller changes for both.Conclusion. Higher levels or interval change in adiponectin and inflammatory markers predict increased mortality in older persons independent of each other, although for adiponectin, the association appears inverse below 20 mg/L. These findings suggest that inflammatory and noninflammatory mechanisms governing aging-related decline operate in parallel and provide a potential explanation for paradoxical adiponectin-outcome associations reported previously.

KW - Adiponectin

KW - Aging

KW - C-reactive protein

KW - Interleukin 6

KW - Mortality

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