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Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials

Kooperbergl, C and Cushman, M and Hsia, J and Robinson, JG and Aragaki, AK and Lynch, JK and Baird, AE and Johnson, KC and Kuller, LH and Beresford, SAA and Rodriguez, B (2007) Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials. PLoS Clinical Trials, 2 (6).

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Abstract

Objective: The Women's Health Initiative hormone trials identified a 44% increase in ischemic stroke risk with combination estrogen plus progestin and a 39% increase with estrogen alone. We undertook a case-control biomarker study to elucidate underlying mechanisms, and to potentially identify women who would be at lower or higher risk for stroke with postmenopausal hormone therapy (HT). Design: The hormone trials were randomized, double-blind, and placebo controlled. Setting: The Women's Health Initiative trials were conducted at 40 clinical centers in the United States. Participants: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. Interventions: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. Outcome Measures: Stroke was ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. Results: No baseline clinical characteristics, including gene polymorphisms, identified women for whom the stroke risk from HT was higher. Paradoxically, women with higher baseline levels of some stroke-associated biomarkers had a lower risk of stroke when assigned to estrogen plus progestin compared to placebo. For example, those with higher IL-6 were not at increased stroke risk when assigned to estrogen plus progestin (odds ratio 1.28) but were when assigned to placebo (odds ratio 3.47; p for difference = 0.02). Similar findings occurred for high baseline PAP, leukocyte count, and D-dimer. However, only an interaction of D-dimer during follow-up interaction with HT and stroke was marginally significant (p = 0.03). Conclusions: Biomarkers did not identify women at higher stroke risk with postmenopausal HT. Some biomarkers appeared to identify women at lower stroke risk with estrogen plus progestin, but these findings may be due to chance.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kooperbergl, C
Cushman, M
Hsia, J
Robinson, JG
Aragaki, AK
Lynch, JK
Baird, AE
Johnson, KC
Kuller, LHKullerL@edc.pitt.eduKULLER
Beresford, SAA
Rodriguez, B
Date: 15 June 2007
Date Type: Publication
Journal or Publication Title: PLoS Clinical Trials
Volume: 2
Number: 6
DOI or Unique Handle: 10.1371/journal.pctr.0020028
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
PubMed ID: 17571161
Date Deposited: 12 Jul 2012 13:12
Last Modified: 30 Oct 2018 13:59
URI: http://d-scholarship.pitt.edu/id/eprint/12873

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