title: Longitudinal changes in adiponectin and inflammatory markers and relation to survival in the oldest old: the Cardiovascular Health Study All Stars study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York, USA. jok2007@med.cornell.edu
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Kizer
authors.forename: Alice M
authors.initials: AM
authors.lastname: Arnold
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Elsa S
authors.initials: ES
authors.lastname: Strotmeyer
authors.forename: Diane G
authors.initials: DG
authors.lastname: Ives
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Ding
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.forename: Paulo H M
authors.initials: PH
authors.lastname: Chaves
authors.forename: Calvin H
authors.initials: CH
authors.lastname: Hirsch
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009026:Mortality / Q000639:trends*; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014481:United States
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein