Advances in Stroke: Stroke in Women

HomeStrokeVol. 53, No. 2Advances in Stroke: Stroke in Women Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessResearch ArticlePDF/EPUBAdvances in Stroke: Stroke in Women Cheryl D. Bushnell, MD, MHS and Moira K. Kapral, MD, MSc Cheryl D. BushnellCheryl D. Bushnell Correspondence to: Cheryl D. Bushnell, MD, MHS, Wake Forest School of Medicine, Medical Center Blvd, Winston Salem, NC 27157. Email E-mail Address: [email protected] Department of Neurology, Wake Forest School of Medicine, Winston Salem, NC (C.D.B). and Moira K. KapralMoira K. Kapral Department of Medicine, University of Toronto, ON, Canada (M.K.K.). Originally published24 Jan 2022https://doi.org/10.1161/STROKEAHA.121.036975Stroke. 2022;53:605–607This article summarizes new knowledge in the field of stroke in women. Recent evidence suggests that stroke incidence may be increased in young women relative to young men, that women with a history of stroke have low risk of pregnancy complications, and that women with pregnancy complications such as preeclampsia and preterm delivery may be at increased risk of stroke for many years after childbearing. Lastly, the representation and reporting of women in clinical trials of acute stroke continues to be suboptimal.Stroke Incidence May Be Higher in Young Women Than in Young MenRecent studies have identified important variations in stroke incidence by sex and age. A retrospective cohort study of 5.8 million enrollees in a US health insurance database between 2001 and 2014 found a lower stroke incidence in men than in women before the age of 44 years, with an incidence rate ratio for men to women aged 15 to 24 years of 0.80 (95% CI, 0.60–1.07), an incidence rate ratio for those aged 24 to 34 years of 0.70 (95% CI, 0.57–0.86), and an incidence rate ratio for those aged 35 to 44 years of 0.87 (95% CI, 0.78–0.98).1 A population-based study from the Netherlands that used administrative data to identify incident strokes between 1998 and 2010 also found an increased stroke incidence in women compared with men in those aged 18 to 44 years,2 and a cohort study of 9.3 million Canadian adults followed from 2003 to 2018 found an increased stroke incidence in women compared with men in those aged under 30 years.3 In contrast, an analysis of 1.3 million people in the Greater Cincinnati/Northern Kentucky Stroke Study found similar stroke incidence rates in women and men aged under 45 years.4 These findings support the need for further study to understand and address the causes and risk factors of stroke in young women.Are Women With a History of Stroke at Risk for Pregnancy Complications?A population-based study from New South Wales, Australia, compared pregnancy outcomes in women with a history of stroke to women with no prior stroke.5 Among the cohort of 487 767 women aged 15 to 44 years, 124 women with stroke (40% ischemic, 23% subarachnoid hemorrhage, and 15% intracerebral hemorrhage) were identified. There were no differences in major characteristics except for smoking and younger age. Women with stroke were more likely to have prelabor Cesarean delivery (odds ratio, 2.83 [95% CI, 2.20–3.63]) and early-term (37–38 weeks) delivery (odds ratio, 1.49 [95% CI, 1.17–1.90]) compared with those without prior stroke; however, there were no differences in other maternal outcomes or in infant outcomes. Although the study was limited by a lack of information on risk factors beyond diabetes, hypertension, and smoking, it does provide some reassuring data for women who are concerned about getting pregnant after having a stroke and suggests that planning for delivery should be discussed among the patient, obstetrician, and the stroke neurology team.What Is the Impact of Preeclampsia on Stroke Risk When Time-Varying Factors Are Considered?Hypertensive disorders of pregnancy have been shown in systematic reviews and in the UK Million Women Study to be an independent risk factor for stroke and cardiovascular disease broadly later in life.6,7 The lasting impact of whether an event at the time of pregnancy might lead to life-long stroke risk is not well established, however. For example, an analysis from the Nurses' Health Study suggested that hypertensive disorders of pregnancy added to a 10-year cardiovascular disease risk prediction score may only be significant in women aged 40 to 49 years and not women over 50 years of age.8 A similar study from Norway showed that preeclampsia history was significant in predicting cardiovascular disease, but there were only small improvements in the ability to predict overall risk when other established risk factors were considered.9 A recent analysis of the Framingham Heart Study, however, found that a history of preeclampsia was independently associated with a ≈4-fold risk (relative risk, 3.79 [95% CI, 1.24–11.60]; P=0.02) of stroke on average over 30 years after the event when time-varying covariates (eg, blood pressure variation over many study visits) were included in the analysis. Although generalizability is limited because this cohort included only White women, this result is important because of the systematic collection of risk factor control over decades and the control for potential bias from time-varying covariates.10The Latest on Preterm Delivery and Risk of Stroke Later in LifePreterm delivery is another sex-specific risk factor that has been shown to increase future risks of hypertension, diabetes, and hyperlipidemia,11 but determination of future stroke risk is challenging because of the risks of confounding from genetic or familial determinants of both preterm delivery and stroke. A population-based study from the Swedish Medical Birth Register with over 2 million women evaluated the association between preterm delivery and stroke over 40 years of follow-up and included not only established risk factors and hypertensive disorders of pregnancy but also cosibling (sister) outcomes to account for genetic and environmental influences on future stroke.12 Overall, preterm (<37 weeks of gestation) delivery was associated with a 40% increased risk of stroke (relative risk, 1.41 [95% CI, 1.29–1.55]) over 43 years after pregnancy, after adjusting for established risk factors and cosibling factors. Preterm delivery was associated with a similar increase in the risk of both ischemic and hemorrhagic strokes. The risk of stroke was reduced by 5% per week closer to term delivery. Overall, this comprehensive analysis should motivate future research on primary prevention strategies beginning early after childbearing, given this sustained impact of preterm delivery on the risk of stroke.Persistent Gaps in Sex- and Gender-Based Stroke ResearchIncorporating sex and gender into study design, analysis and interpretation is critical for producing research that is broadly generalizable and applicable to populations. To facilitate this, many research funders now require applicants to describe how sex will be addressed in their research plans,13 and the Sex and Gender Equity in Research guidelines provide direction to authors and journals on how best to report sex and gender information in manuscripts.14 Despite this, a recent review of 115 randomized trials of acute stroke published between 2010 and 2020 found that overall, only 37% reported results by sex.15 Although there were improvements over time, even in 2020, only 48% of trials reported results by sex. In addition, a meta-analysis of these trials found that women were less likely than men to be enrolled across all regions and study types and that this was in large part driven by the exclusion of people aged over 80 years.16 Collectively, these findings suggest that investigators should review trial eligibility criteria to ensure that older women are not being excluded from stroke trials unnecessarily and that authors and journals should ensure that manuscripts adhere to reporting recommendations related to sex and gender.Article InformationSources of FundingDr Kapral holds the Lillian Love Chair in Women's Health at the University Health Network/University of Toronto. Dr Bushnell receives research salary support from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (U24 NS107235), Agency for Healthcare Research Quality (R01 HS02572), Patient Centered Outcomes Research Institute (PCS 1403-14532), and NIH/National Center for Advancing Translational Sciences (UL1 TR001420).DisclosuresDr Bushnell has ownership interest in Care Directions, LLC. The other author reports no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Sources of Funding and Disclosures, see page 606.Correspondence to: Cheryl D. Bushnell, MD, MHS, Wake Forest School of Medicine, Medical Center Blvd, Winston Salem, NC 27157. Email [email protected]eduReferences1. Leppert MH, Ho PM, Burke J, Madsen TE, Kleindorfer D, Sillau S, Daugherty S, Bradley CJ, Poisson SN. Young women had more strokes than young men in a large, United States claims sample.Stroke. 2020; 51:3352–3355. doi: 10.1161/STROKEAHA.120.030803LinkGoogle Scholar2. Ekker MS, Verhoeven JI, Vaartjes I, van Nieuwenhuizen KM, Klijn CJM, de Leeuw FE. Stroke incidence in young adults according to age, subtype, sex, and time trends.Neurology. 2019; 92:e2444–e2454. doi: 10.1212/WNL.0000000000007533CrossrefMedlineGoogle Scholar3. Vyas MV, Silver FL, Austin PC, Yu AYX, Pequeno P, Fang J, Laupacis A, Kapral MK. Stroke incidence by sex across the lifespan.Stroke. 2021; 52:447–451. doi: 10.1161/STROKEAHA.120.032898LinkGoogle Scholar4. Madsen TE, Khoury JC, Leppert M, Alwell K, Moomaw CJ, Sucharew H, Woo D, Ferioli S, Martini S, Adeoye O, et al.. Temporal trends in stroke incidence over time by sex and age in the GCNKSS.Stroke. 2020; 51:1070–1076. doi: 10.1161/STROKEAHA.120.028910LinkGoogle Scholar5. Austin K, Seeho S, Ibiebele I, Ford J, Morris J, Torvaldsen S. Pregnancy outcomes for women with a history of stroke: a population-based record linkage study.Aust N Z J Obstet Gynaecol. 2021; 61:239–243. doi: 10.1111/ajo.13267Google Scholar6. Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, Zaman A, Fryer AA, Kadam U, Chew-Graham CA, et al.. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis.Circ Cardiovasc Qual Outcomes. 2017; 10:e003497. doi: 10.1161/CIRCOUTCOMES.116.003497LinkGoogle Scholar7. Canoy D, Cairns BJ, Balkwill A, Wright FL, Khalil A, Beral V, Green J, Reeves G; Million Women Study Collaborators. Hypertension in pregnancy and risk of coronary heart disease and stroke: a prospective study in a large UK cohort.Int J Cardiol. 2016; 222:1012–1018. doi: 10.1016/j.ijcard.2016.07.170CrossrefMedlineGoogle Scholar8. Stuart JJ, Tanz LJ, Cook NR, Spiegelman D, Missmer SA, Rimm EB, Rexrode KM, Mukamal KJ, Rich-Edwards JW. Hypertensive disorders of pregnancy and 10-year cardiovascular risk prediction.J Am Coll Cardiol. 2018; 72:1252–1263. doi: 10.1016/j.jacc.2018.05.077CrossrefMedlineGoogle Scholar9. Markovitz AR, Stuart JJ, Horn J, Williams PL, Rimm EB, Missmer SA, Tanz LJ, Haug EB, Fraser A, Timpka S, et al.. Does pregnancy complication history improve cardiovascular disease risk prediction? Findings from the HUNT study in Norway.Eur Heart J. 2019; 40:1113–1120. doi: 10.1093/eurheartj/ehy863CrossrefMedlineGoogle Scholar10. de Havenon A, Delic A, Stulberg E, Sheibani N, Stoddard G, Hanson H, Theilen L. Association of preeclampsia with incident stroke in later life among women in the Framingham Heart Study.JAMA Netw Open. 2021; 4:e215077. doi: 10.1001/jamanetworkopen.2021.5077Google Scholar11. Tanz LJ, Stuart JJ, Williams PL, Missmer SA, Rimm EB, James-Todd TM, Rich-Edwards JW. Preterm delivery and maternal cardiovascular disease risk factors: the Nurses' Health Study II.J Womens Health (Larchmt). 2019; 28:677–685. doi: 10.1089/jwh.2018.7150CrossrefMedlineGoogle Scholar12. Crump C, Sundquist J, Sundquist K. Preterm delivery and long-term risk of stroke in women: a national cohort and cosibling study.Circulation. 2021; 143:2032–2044. doi: 10.1161/CIRCULATIONAHA.120.052268LinkGoogle Scholar13. Clayton JA. Applying the new SABV (sex as a biological variable) policy to research and clinical care.Physiol Behav. 2018; 187:2–5. doi: 10.1016/j.physbeh.2017.08.012Google Scholar14. Heidari S, Babor TF, De Castro P, Tort S, Curno M. Sex and Gender Equity in Research: rationale for the SAGER guidelines and recommended use.Res Integr Peer Rev. 2016; 1:2. doi: 10.1186/s41073-016-0007-6CrossrefMedlineGoogle Scholar15. Pudar J, Strong B, Howard VJ, Reeves MJ. Reporting of results by sex in randomized controlled trials of acute stroke therapies (2010-2020).Stroke. 2021; 52:e702–e705. doi: 10.1161/STROKEAHA.120.034099LinkGoogle Scholar16. Strong B, Pudar J, Thrift AG, Howard VJ, Hussain M, Carcel C, de Los Campos G, Reeves MJ. Sex disparities in enrollment in recent randomized clinical trials of acute stroke: a meta-analysis.JAMA Neurol. 2021; 78:666–677. doi: 10.1001/jamaneurol.2021.0873CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Hänsel M, Steigmiller K, Luft A, Gebhard C, Held U and Wegener S (2022) Neurovascular disease in Switzerland: 10‐year trends show non‐traditional risk factors on the rise and higher exposure in women, European Journal of Neurology, 10.1111/ene.15434 February 2022Vol 53, Issue 2Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.121.036975PMID: 35073191 Originally publishedJanuary 24, 2022 Keywordsstrokecerebrovascular diseasepregnancypremature birthfemaleinfant, newbornPDF download Advertisement