Higher Incidence Of Ischemic Stroke In Young Women Than In Young Men Mind The Gap

HomeStrokeVol. 51, No. 11Higher Incidence of Ischemic Stroke in Young Women Than in Young Men Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBHigher Incidence of Ischemic Stroke in Young Women Than in Young MenMind the Gap Merel S. Ekker, MD and Frank-Erik de Leeuw, MD, PhD Merel S. EkkerMerel S. Ekker Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands. Search for more papers by this author and Frank-Erik de LeeuwFrank-Erik de Leeuw Correspondence to: Frank-Erik de Leeuw, MD, PhD, Radboud University Medical Centre, Department of Neurology (935), PO Box 9101, 6500 HB Nijmegen, the Netherlands. Email E-mail Address: [email protected] https://orcid.org/0000-0003-2221-3026 Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands. Search for more papers by this author Originally published18 Sep 2020https://doi.org/10.1161/STROKEAHA.120.032062Stroke. 2020;51:3195–3196This article is a commentary on the followingYoung Women Had More Strokes Than Young Men in a Large, United States Claims SampleOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: September 18, 2020: Ahead of Print There is more and more evidence of gender disparities in the occurrence, risk factors and causes, and outcome of ischemic stroke.1,2 These differences are illustrated by European population-based studies that showed a higher stroke incidence in young women, with age varying from 15 to 44 years, than in men.3–7 Although not all studies reported unequivocal results, as illustrated by another European and Asian study reporting a similar incidence between men and women in the younger age groups (18–35 and 20–40 years) and an even higher incidence in men over 35 or 40 years.8,9See related article, p 3352In this issue of Stroke, results of Leppert et al10 may shed more light on these discrepancies by investigating a large number of young cases (n=5198) and by extending the results on the occurrence of ischemic stroke in young adults to a United States population. They found an incidence rate ratio of 0.7 for young (aged 25–44 years) men compared with young women, based on insurance claims data.10 This is an alarming finding of a disease that strikes at fertile age, at a time that young women are preparing for a study, planning families, work or decisive career moves. This important finding suggests that there are women-specific risk factors and causes that lead to a higher incidence of ischemic stroke at young age in women then in men, although findings based on administrative data should be interpreted with care, as acknowledged by the authors.First, selection bias may have played a role as it seems plausible that having health care insurance is related to the risk of ischemic stroke which may differ from noninsured people, and even gender inequalities might exist in terms of health care insurance. Second, misclassification may have occurred as stroke mimics may not always have been recoded once a definite diagnosis has been made. A frequently occurring stroke mimic includes migraine with aura, which is overrepresented among women, which may easily be misclassified as ischemic stroke.11 These methodological explanations may, at least in part, explain a higher incidence of (presumed) ischemic stroke in young women. Another common limitation of using administrative databases is the lack of phenotypic detail, and this study is no exception with no information on risk factors and causes of stroke.However, based on cohort studies, there is some limited evidence for women-specific risk factors that may provide a rationale for the findings by Leppert et al,10 that may also serve as a starting point for research towards gender-tailored management of ischemic stroke. Putaala et al6 found an increased risk of ischemic stroke during pregnancy with about 2.5% of all ischemic strokes in young women explained by pregnancy. They also found a higher occurrence of patent foramen ovale and atrial septum defects in women.6 With a patent foramen ovale prevalence only slightly higher in patients with stroke compared with stroke free population12,13 the causal relation with first-ever stroke needs to be further investigated, especially since patent foramen ovale closure trials have reported a lower risk of recurrent ischemic stroke in patients who underwent patent foramen ovale closure versus those on optimal medical therapy.14 Other putative risk factors for ischemic stroke that are overrepresented among young women include migraine (with aura), auto-immune disorders, oral contraception, and hormone replacement therapy.6,15,16 Still, these women-specific risk factors do not seem to explain the entire gap in incidence of young stroke between men and women.The findings of Leppert et al10 are, therefore, encouraging to search for additional explanations. As the incidence of ischemic stroke is especially higher in women in the youngest age strata (<35 years), hormonal,1 lifestyle and cultural differences are likely candidates for further research. The combination of the unexplained gender gap in ischemic stroke incidence and the large proportion of cryptogenic strokes and strokes with uncertain or multiple possible causes6,17 in young women calls for further research. Given the fact that ischemic stroke among very young women (<30 years) occurs rarely, studies should be large, preferably collaborative with extensive phenotyping available with some of them already ongoing such as the SiPP study (Stroke in Pregnancy and Postpartum),18 SECRETO19 study (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome) and ODYSSEY20 study (Observational Dutch Young Symptomatic Stroke Study).To conclude, highlighting the higher incidence of ischemic stroke at young age in women, Leppert et al10 take a first important step in closing this gender gap. While current treatment strategies are based on results of secondary prevention trials in which both women and young adults were underrepresented, a better understanding of the underlying etiological differences of ischemic stroke between men and women will provide stepping stones for the development of personalized, sex-specific therapy.DisclosuresDr de Leeuw is an associate editor of the International Journal of Stroke, and supported by a clinical established investigator grant from the Dutch Heart Foundation (2014 T060). The other author reports no conflicts.FootnotesFor Disclosures, see page 3196.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to: Frank-Erik de Leeuw, MD, PhD, Radboud University Medical Centre, Department of Neurology (935), PO Box 9101, 6500 HB Nijmegen, the Netherlands. Email frankerik.[email protected]nlReferences1. 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Olié V, Grave C, Tuppin P, Duloquin G, Béjot Y and Gabet A (2022) Patients Hospitalized for Ischemic Stroke and Intracerebral Hemorrhage in France: Time Trends (2008–2019), In-Hospital Outcomes, Age and Sex Differences, Journal of Clinical Medicine, 10.3390/jcm11061669, 11:6, (1669) Norman K, Eriksson M and von Euler M (2022) Sex Differences in Ischemic Stroke Within the Younger Age Group: A Register-Based Study, Frontiers in Neurology, 10.3389/fneur.2022.793181, 13 Basu E, Salehi Omran S, Kamel H and Parikh N (2021) Sex differences in the risk of recurrent ischemic stroke after ischemic stroke and transient ischemic attack, European Stroke Journal, 10.1177/23969873211058568, 6:4, (367-373), Online publication date: 1-Dec-2021. Related articlesYoung Women Had More Strokes Than Young Men in a Large, United States Claims SampleMichelle H. Leppert, et al. Stroke. 2020;51:3352-3355 November 2020Vol 51, Issue 11 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.120.032062PMID: 32942968 Originally publishedSeptember 18, 2020 Keywordsmigraine with auraincidenceselection biasrisk factorsyoung adultEditorialsPDF download Advertisement SubjectsEpidemiologyIschemic StrokeWomen, Sex, and Gender