Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy

Jacques E. Rossouw, Karen Johnson, Mary Pettinger, Mary Cushman, Per Morten Sandset, Lewis Kuller, Frits Rosendaal, Jan Rosing, Sylvia Wasserthal-Smoller, Lisa W. Martin, Joann E. Manson, Kamakshi Lakshminarayan, Jose G. Merino, John Lynch

Research output: Contribution to journalArticle

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Abstract

Background and Purpose-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.

Original languageEnglish (US)
Pages (from-to)952-957
Number of pages6
JournalStroke
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2012

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Activated Protein C Resistance
Stroke
Hormones
Therapeutics
Lacunar Stroke
Women's Health
lipoprotein-associated coagulation inhibitor
Case-Control Studies
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy. / Rossouw, Jacques E.; Johnson, Karen; Pettinger, Mary; Cushman, Mary; Sandset, Per Morten; Kuller, Lewis; Rosendaal, Frits; Rosing, Jan; Wasserthal-Smoller, Sylvia; Martin, Lisa W.; Manson, Joann E.; Lakshminarayan, Kamakshi; Merino, Jose G.; Lynch, John.

In: Stroke, Vol. 43, No. 4, 01.04.2012, p. 952-957.

Research output: Contribution to journalArticle

Rossouw, JE, Johnson, K, Pettinger, M, Cushman, M, Sandset, PM, Kuller, L, Rosendaal, F, Rosing, J, Wasserthal-Smoller, S, Martin, LW, Manson, JE, Lakshminarayan, K, Merino, JG & Lynch, J 2012, 'Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy', Stroke, vol. 43, no. 4, pp. 952-957. https://doi.org/10.1161/STROKEAHA.111.643072
Rossouw, Jacques E. ; Johnson, Karen ; Pettinger, Mary ; Cushman, Mary ; Sandset, Per Morten ; Kuller, Lewis ; Rosendaal, Frits ; Rosing, Jan ; Wasserthal-Smoller, Sylvia ; Martin, Lisa W. ; Manson, Joann E. ; Lakshminarayan, Kamakshi ; Merino, Jose G. ; Lynch, John. / Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy. In: Stroke. 2012 ; Vol. 43, No. 4. pp. 952-957.
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T1 - Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy

AU - Rossouw, Jacques E.

AU - Johnson, Karen

AU - Pettinger, Mary

AU - Cushman, Mary

AU - Sandset, Per Morten

AU - Kuller, Lewis

AU - Rosendaal, Frits

AU - Rosing, Jan

AU - Wasserthal-Smoller, Sylvia

AU - Martin, Lisa W.

AU - Manson, Joann E.

AU - Lakshminarayan, Kamakshi

AU - Merino, Jose G.

AU - Lynch, John

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Background and Purpose-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.

AB - Background and Purpose-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.

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