title: Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy.
abstract: OBJECTIVE
  To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized activated protein C resistance ratio [nAPCsr]) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy.
  
  
  METHODS
  Nested case-control study of 455 cases of ischemic stroke and 565 matched control subjects in the Women's Health Initiative trials of postmenopausal hormone therapy.
  
  
  RESULTS
  Baseline free TFPI was associated with ischemic stroke risk (OR per SD increase, 1.17; 95% CI, 1.01-1.37; P=0.039), but baseline nAPCsr was not (OR per SD increase, 0.89; 95% CI, 0.75-1.05; P=0.15). Baseline TFPI levels and nAPCsr did not modify the effect of postmenopausal hormone therapy on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction P=0.452 and 0.971, respectively). In subgroup analyses, baseline nAPCsr was inversely associated with lacunar strokes (OR per SD increase, 0.74; 95% CI, 0.57-0.96; P=0.025) and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes (P=0.008).
  
  
  CONCLUSIONS
  Procoagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to postmenopausal hormone therapy.  Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT 00000611.
authors.affiliation: National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Room 9192, Bethesda, MD 20892, USA. rossouwj@nih.gov
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Rossouw
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Mary
authors.initials: M
authors.lastname: Pettinger
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Per Morten
authors.initials: PM
authors.lastname: Sandset
authors.forename: Lewis
authors.initials: L
authors.lastname: Kuller
authors.forename: Frits
authors.initials: F
authors.lastname: Rosendaal
authors.forename: Jan
authors.initials: J
authors.lastname: Rosing
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wasserthal-Smoller
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Kamakshi
authors.initials: K
authors.lastname: Lakshminarayan
authors.forename: Jose G
authors.initials: JG
authors.lastname: Merino
authors.forename: John
authors.initials: J
authors.lastname: Lynch
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood*; D000368:Aged; D002545:Brain Ischemia / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D011486:Protein C / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000453:epidemiology*
chemical_list: D008074:Lipoproteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor