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January 22, 2019; 92 (4) Article

Aspirin reduces long-term stroke risk in women with prior hypertensive disorders of pregnancy

View ORCID ProfileEliza C. Miller, View ORCID ProfileAmelia K. Boehme, Nadia T. Chung, Sophia S. Wang, James V. Lacey, View ORCID ProfileKamakshi Lakshminarayan, Charlie Zhong, Daniel Woo, View ORCID ProfileNatalie A. Bello, View ORCID ProfileRonald Wapner, View ORCID ProfileMitchell S.V. Elkind, View ORCID ProfileJoshua Z. Willey
First published December 26, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006815
Eliza C. Miller
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Amelia K. Boehme
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Nadia T. Chung
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Sophia S. Wang
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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James V. Lacey Jr
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Kamakshi Lakshminarayan
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Charlie Zhong
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Daniel Woo
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Natalie A. Bello
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Ronald Wapner
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Mitchell S.V. Elkind
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Joshua Z. Willey
From the Departments of Neurology (E.C.M., A.K.B., M.S.V.E., J.Z.W.), Medicine (N.A.B.), and Obstetrics and Gynecology (R.W.), Columbia University; Department of Epidemiology (A.K.B., M.S.V.E.), Columbia University Mailman School of Public Health, New York, NY; Department of Population Sciences (N.T.C., S.S.W., J.V.L., C.Z.), Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; Department of Neurology (K.L.), University of Minnesota Medical Center, Minneapolis; and Department of Neurology (D.W.), University of Cincinnati Medical Center, OH.
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Citation
Aspirin reduces long-term stroke risk in women with prior hypertensive disorders of pregnancy
Eliza C. Miller, Amelia K. Boehme, Nadia T. Chung, Sophia S. Wang, James V. Lacey, Kamakshi Lakshminarayan, Charlie Zhong, Daniel Woo, Natalie A. Bello, Ronald Wapner, Mitchell S.V. Elkind, Joshua Z. Willey
Neurology Jan 2019, 92 (4) e305-e316; DOI: 10.1212/WNL.0000000000006815

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Abstract

Objective To determine whether hypertensive disorders of pregnancy (HDP) increased long-term stroke risk in women in the California Teachers Study (CTS), a prospective cohort study, and whether aspirin or statin use modified this risk.

Methods CTS participants ≤60 years of age at the time of enrollment in 1995 were followed up prospectively for validated stroke outcomes obtained via linkage with California hospital records through December 31, 2015. We calculated unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the primary outcomes of all stroke and stroke before 60 years of age among those with and without a history of HDP. We tested for interactions (p < 0.2) and performed stratified analyses to assess the risk of the primary outcomes in women with and without self-reported use of aspirin or statins.

Results Of 83,749 women included in the analysis, 4,070 (4.9%) had HDP. Women with prior HDP had increased risk of all stroke (adjusted HR 1.3, 95% CI 1.2–1.4) but no increased risk of stroke before age 60 (adjusted HR 1.2, 95% CI 0.9–1.7). There was an interaction (p = 0.18) between aspirin use and HDP history on risk of stroke before age 60: nonusers of aspirin had higher risk (adjusted HR 1.5, 95% CI 1.0–2.1) while aspirin users did not (adjusted HR 0.8, 95% CI 0.4–1.7). This effect was not seen with statins.

Conclusions After controlling for comorbid conditions, women with prior HDP had increased long-term stroke risk, which was reduced by aspirin use. Randomized trials may be needed to assess whether long-term aspirin use could benefit selected women with a history of HDP.

Glossary

CI=
confidence interval;
CTS=
California Teachers Study;
HDP=
hypertensive disorders of pregnancy;
HR=
hazard ratio;
ICD-9=
International Classification of Diseases, 9th Revision;
OR=
odds ratio

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial page 159

  • Podcast: NPub.org/1ungrh

  • Received May 4, 2018.
  • Accepted in final form September 17, 2018.
  • © 2018 American Academy of Neurology
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