title: Prospective associations between inflammatory and hemostatic markers and physical functioning limitations in mid-life women: Longitudinal results of the Study of Women's Health Across the Nation (SWAN).
abstract: BACKGROUND
  Due to the public health burden of age-related declines in physical functioning, it is important to identify targets for intervention for the prevention of functional decline. We prospectively examined whether higher levels of inflammatory and hemostatic markers (high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA-ag), fibrinogen, and Factor VIIc (FVIIc)) were prospectively associated with reporting greater limitations in perceived physical functioning, and explored potential racial differences in the associations, in a multi-ethnic sample of mid-life women.
  
  
  METHODS
  Women (45-56 years) in the Study of Women's Health Across the Nation who completed the physical functioning scale of the Medical Outcome Short Form (SF-36) at follow-up visits 4, 6, or 8 and had inflammatory/hemostatic measures in the preceding year were included (n=2296). The continuous SF-36 physical function score was categorized as: no limitation (86-100 points), some limitation (51-85 points), and substantial limitation (0-50 points). Physical function category at time t was modeled a function of each biomarker, separately, at time t-1 using ordinal generalized estimating equations.
  
  
  RESULTS
  After adjusting for age, race/ethnicity, body size, sociodemographic, medical and lifestyle factors, higher levels of tPA-ag and hs-CRP were associated with subsequently reporting greater limitations in physical functioning, although the latter was only marginally significant (p=0.13). For each standard deviation (SD) increase in logtPA-ag, the odds of some or substantial limitations was 1.18 (95%CI 1.09,1.27); for each SD increase in loghs-CRP, the odds of some or substantial limitation was (1.08, 95%CI 0.98,1.19). In African American women only, higher fibrinogen levels were associated with subsequently reporting greater limitations (OR=1.30, 95%CI 1.13,1.50, for each one SD increase in fibrinogen).
  
  
  CONCLUSIONS
  Higher levels of inflammatory and hemostatic markers were prospectively associated with greater limitations in perceived physical functioning in mid-life women.
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, USA. Electronic address: mcclurec@edc.pitt.edu.
authors.forename: Candace K
authors.initials: CK
authors.lastname: McClure
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, USA.
authors.forename: Samar R
authors.initials: SR
authors.lastname: El Khoudary
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Karvonen-Gutierrez
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Ylitalo
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Tomey
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, USA.
authors.forename: Trang
authors.initials: T
authors.lastname: VoPham
authors.affiliation: Kaiser Permanente Division of Research, Oakland, CA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sternfeld
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, USA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, USA.
authors.forename: Siobán
authors.initials: S
authors.lastname: Harlow
mesh_terms: D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000208:ethnology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000097:blood*; D008137:Longitudinal Studies; D008593:Menopause / Q000097:blood / Q000208:ethnology / Q000502:physiology; D008875:Middle Aged; D051346:Mobility Limitation; D009043:Motor Activity / Q000502:physiology; D011446:Prospective Studies; D012959:Socioeconomic Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014481:United States / Q000453:epidemiology; D016387:Women's Health / Q000208:ethnology / Q000706:statistics & numerical data*
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator
keywords: Hemostasis; Inflammation; Menopausal transition; Physical functioning; Women