Can Biomarkers Identify Women at Increased Stroke Risk? The Women's Health Initiative Hormone Trials
Open Access
- 15 June 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Clinical Trials
- Vol. 2 (6), e28
- https://doi.org/10.1371/journal.pctr.0020028
Abstract
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). The hormone trials were randomized, double-blind, and placebo controlled. The Women's Health Initiative trials were conducted at 40 clinical centers in the United States. The trials enrolled 27,347 postmenopausal women, aged 50–79 y. 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. 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. 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). 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. ClnicalTrials.gov NCT00000611Keywords
This publication has 21 references indexed in Scilit:
- Relations of Serum High-Sensitivity C-Reactive Protein and Interleukin-6 Levels With Silent Brain InfarctionStroke, 2005
- The Association Between Lipid Levels and the Risks of Incident Myocardial Infarction, Stroke, and Total Mortality: The Cardiovascular Health StudyJournal of the American Geriatrics Society, 2004
- Effects of Conjugated Equine Estrogen in Postmenopausal Women With HysterectomyJAMA, 2004
- The women's health initiative recruitment methods and resultsAnnals of Epidemiology, 2003
- The women's health initiative postmenopausal hormone trials: overview and baseline characteristics of participantsAnnals of Epidemiology, 2003
- Outcomes ascertainment and adjudication methods in the women's health initiativeAnnals of Epidemiology, 2003
- Effect of Estrogen Plus Progestin on Stroke in Postmenopausal WomenJAMA, 2003
- Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled TrialJAMA, 2002
- Hemostatic Markers in Patients at Risk of Cerebral IschemiaStroke, 2000
- Statistical validation of intermediate endpoints for chronic diseasesStatistics in Medicine, 1992