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

Charles Kooperbergl, Mary Cushman, Judith Hsia, Jennifer G. Robinson, Aaron K. Aragaki, John K. Lynch, Alison E. Baird, Karen Johnson, Lewis H. Kuller, Shirley A A Beresford, Beatriz Rodriguez

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere28
JournalPLoS Clinical Trials
Volume2
Issue number6
DOIs
StatePublished - Jun 15 2007

Fingerprint

Women's Health
Biomarkers
Stroke
Hormones
Estrogens
Progestins
Placebos
Conjugated (USP) Estrogens
Odds Ratio
Medroxyprogesterone Acetate
Therapeutics
Hysterectomy
Leukocyte Count
Uterus
Case-Control Studies
Interleukin-6
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Pharmacology (medical)

Cite this

Kooperbergl, C., Cushman, M., Hsia, J., Robinson, J. G., Aragaki, A. K., Lynch, J. K., ... Rodriguez, B. (2007). Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials. PLoS Clinical Trials, 2(6), [e28]. https://doi.org/10.1371/journal.pctr.0020028

Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials. / Kooperbergl, Charles; Cushman, Mary; Hsia, Judith; Robinson, Jennifer G.; Aragaki, Aaron K.; Lynch, John K.; Baird, Alison E.; Johnson, Karen; Kuller, Lewis H.; Beresford, Shirley A A; Rodriguez, Beatriz.

In: PLoS Clinical Trials, Vol. 2, No. 6, e28, 15.06.2007.

Research output: Contribution to journalArticle

Kooperbergl, C, Cushman, M, Hsia, J, Robinson, JG, Aragaki, AK, Lynch, JK, Baird, AE, Johnson, K, Kuller, LH, Beresford, SAA & Rodriguez, B 2007, 'Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials', PLoS Clinical Trials, vol. 2, no. 6, e28. https://doi.org/10.1371/journal.pctr.0020028
Kooperbergl, Charles ; Cushman, Mary ; Hsia, Judith ; Robinson, Jennifer G. ; Aragaki, Aaron K. ; Lynch, John K. ; Baird, Alison E. ; Johnson, Karen ; Kuller, Lewis H. ; Beresford, Shirley A A ; Rodriguez, Beatriz. / Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials. In: PLoS Clinical Trials. 2007 ; Vol. 2, No. 6.
@article{d0fc675ad04744dc91ad5d2c5d09b3ce,
title = "Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials",
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.",
author = "Charles Kooperbergl and Mary Cushman and Judith Hsia and Robinson, {Jennifer G.} and Aragaki, {Aaron K.} and Lynch, {John K.} and Baird, {Alison E.} and Karen Johnson and Kuller, {Lewis H.} and Beresford, {Shirley A A} and Beatriz Rodriguez",
year = "2007",
month = "6",
day = "15",
doi = "10.1371/journal.pctr.0020028",
language = "English (US)",
volume = "2",
journal = "PLoS Clinical Trials",
issn = "1555-5887",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Can biomarkers identify women at increased stroke risk? The Women's Health Initiative hormone trials

AU - Kooperbergl, Charles

AU - Cushman, Mary

AU - Hsia, Judith

AU - Robinson, Jennifer G.

AU - Aragaki, Aaron K.

AU - Lynch, John K.

AU - Baird, Alison E.

AU - Johnson, Karen

AU - Kuller, Lewis H.

AU - Beresford, Shirley A A

AU - Rodriguez, Beatriz

PY - 2007/6/15

Y1 - 2007/6/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34250757702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250757702&partnerID=8YFLogxK

U2 - 10.1371/journal.pctr.0020028

DO - 10.1371/journal.pctr.0020028

M3 - Article

VL - 2

JO - PLoS Clinical Trials

JF - PLoS Clinical Trials

SN - 1555-5887

IS - 6

M1 - e28

ER -