title: Inflammation and thrombosis biomarkers and incident frailty in postmenopausal women.
abstract: BACKGROUND
  The immune and blood coagulation systems have been implicated in the pathophysiology of the geriatric syndrome of frailty, but limited prospective data examining the relationship of clotting/inflammation biomarkers to risk of incident frailty exist.
  
  
  METHODS
  This prospective analysis was derived from a nested case-control study within the Women's Health Initiative. Among women 65 to 79 years free of frailty at enrollment, we randomly selected 900 incident cases from those developing frailty within 3 years; 900 non-frail controls were individually matched on age, ethnicity, and blood collection date. Biomarkers assessed for risk of incident frailty included fibrinogen, factor VIII, D-dimer, C-reactive protein, interleukin-6, and tissue plasminogen activator (t-PA).
  
  
  RESULTS
  When examined by quartiles in multivariable adjusted models, higher D-dimer and t-PA levels were each associated with increased risk of frailty (P trend = .04). Relative to the lowest quartile, the odds ratios for frailty compared with the upper quartile were 1.52 (95% confidence interval, 1.05-2.22) for t-PA and 1.57 (95% confidence interval, 1.11-2.22) for D-dimer. For women having high t-PA and high D-dimer compared with women having lower levels of both biomarkers, the odds of frailty was 2.20 (1.29-3.75). There was little evidence for association between coagulation factor VIII, fibrinogen, C-reactive protein, or interleukin-6 levels and incident frailty.
  
  
  CONCLUSIONS
  This prospective analysis supports the role of markers of fibrin turnover and fibrinolysis as independent predictors of incident frailty in postmenopausal women.
authors.affiliation: Women's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA. apreiner@u.washington.edu
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Gray
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Charles L
authors.initials: CL
authors.lastname: Kooperberg
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Woods
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood / Q000502:physiology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016001:Confidence Intervals; D005169:Factor VIII / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005500:Follow-Up Studies; D016330:Frail Elderly; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015999:Multivariate Analysis; D017698:Postmenopause / Q000097:blood* / Q000502:physiology; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D013927:Thrombosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D010959:Tissue Plasminogen Activator / Q000097:blood; D016387:Women's Health
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D005169:Factor VIII; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator
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