Published online before print February 10, 2009, doi: 10.1161/STROKEAHA.109.547471
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2009;40:1027.)
© 2009 American Heart Association, Inc.
Editorials |
Stroke in Women
An Evolving Topic
From INSERM Unit 708-Neuroepidemiology (T.K.) and Pierre et Marie Curie University (T.K.), Paris, France; the Division of Preventive Medicine (T.K.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and Service de Neurologie (M.G.B.), Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, and Diderot University (M.G.B.), Paris, France.
Correspondence to Tobias Kurth, MD, ScD, INSERM Unit 708-Neuroepidemiology, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. E-mail tobias.kurth{at}upmc.fr
Key Words: minorities • risk factors • women
See Go Red for Women section.
Stroke in women is a major health issue that has long been neglected but is now attracting more and more attention.1 Many aspects of stroke are similar in men and women, including clinical presentation, neuroimaging data, main subtypes, and acute treatment. The major conventional risk factors are also the same.2 There are, however, some gender differences and specificities in stroke epidemiology, etiologies with specific causes, risk factors, and preventive treatments, as well as differences in the social impact.
One third of strokes occur among individuals <65 years of age,3 but stroke in women is an ongoing epidemic because of the sharp increase in stroke incidence with increasing age, the rapidly aging population, and the greater longevity of women. Projections indicate that the prevalence and incidence of stroke will increase by 2020 in both genders, but that these figures are magnified in women.4 By 2050, mortality from stroke will be 30% higher in women than men, a figure driven by the age group >85.5 It should also be noted that the social impact of stroke is greater in women because women have poorer functional outcome after stroke with more physical and cognitive impairment, more depression, more limitations in active daily living, and lower quality of life.5 Furthermore, many older women, particularly in wealthy countries, are socially isolated: 8 million women versus 2.7 million men in the United States.6
Earlier in life, causes and risk factors for stroke differ widely according to gender and age; however, after menopause, the main causes of stroke are similar, including large artery atheroma, small vessel disease, and cardiac disease. Postmenopausal hormone use has been associated with a small but statistically significant increase in the risk of stroke in observational studies7 and randomized, controlled trials such as the Women’s Estrogen for Stroke Trial8 and the Women’s Health Initiative.9,10 The risk of stroke was increased for estrogen plus progesterone and estrogen alone, corresponding, however, to a relatively low absolute risk increase of 8 per 10000 women per year.
In women before menopause, although rare, stroke remains a potentially devastating occurrence during pregnancy and the postpartum period. This has specifically been a problem for women with multiple pregnancies11 and eclampsia.12 During the postpartum period, risk of ischemic and hemorrhagic stroke is markedly increased,12 and further studies are needed to identify women who are at particular increased risk after pregnancy. Migraine may be one of these factors.13 Rare but characteristic types of stroke during the postpartum period are cerebral venous thrombosis and postpartum angiopathy (postpartum reversible vasoconstriction syndrome), which should be kept in mind when women report headache, seizures, or/and focal deficits after pregnancy.1
The numerous studies devoted to oral contraceptives and stroke have shown that oral contraceptives containing a high content of estrogen greatly increase the risk of stroke (relative risk around 4), both ischemic and hemorrhagic, whereas oral contraceptives with low estrogen content "only" double the risk of ischemic stroke with a low absolute risk (additional 4 per 100000 women per year).14 Another specific risk factor for stroke in young women is migraine with aura.15,16 Although the absolute risk increase is again considerably low, this risk is particularly high for women with migraine with aura who smoke and/or use oral contraceptives, an association that has been confirmed with very recent data.17 Also intriguing is the fact that the association between migraine with aura and ischemic stroke is particularly strong for women with a rather healthy vascular risk status.18 Women in this age group are also preponderant for rare causes of stroke, including Takayasu arteritis, fibromuscular dysplasia, Susac syndrome (small infarcts of the cochlear, retinal, and encephalic tissue), antiphospholipid antibody syndrome, systemic lupus, Sneddon syndrome, and reversible cerebral vasoconstriction syndrome. These uncommon causes of stroke require specific diagnostic procedures and should be kept in mind when younger women present with stroke.
With regard to treatment, many studies have been devoted to acute stroke care, with conflicting results about gender differences in pre- and in-hospital delay, likelihood in receiving thrombolysis, and frequency of complications such as pneumonia, urinary tract infections, and depression.5 With regard to preventive treatment, the most striking gender difference is the differential effect of low-dose aspirin in the primary prevention of ischemic stroke, indicating a significantly decreased risk in women with no clear benefit in men.19 However, because numerous secondary prevention trials of aspirin do not show a gender difference for recurrent stroke or other ischemic vascular events20 and because dosing of aspirin and follow-up time differed in primary prevention trials of men and women, the reason for this apparent gender difference remains unclear.
Our understanding of stroke in women has been substantially improved over the last decades. Some risk factors have consistently been linked to increased risk of stroke in women and one cannot emphasize enough that smoking is a major contributor of stroke among young women, particularly if women, have migraine with aura and use oral contraceptives. Many open questions in epidemiology, clinical etiology, and outcome of stroke among women remain, however. Substantial efforts by the American Heart Association/Stroke Association with their Go Red for Women campaign have been started and will continue to improve the awareness of cardiovascular disease and stroke in women and will help induce new research efforts.
Future clinical and population-based research in stroke should include specific a priori hypotheses and detailed data collection allowing causal inference of stroke risk factors in women. Because of different risk factor distributions and health behaviors in Africa and eastern European countries as well as Asian countries, specific emphasis should be given to gender differences in stroke occurrence in these regions. Implementation of substudies in large stroke registries will allow specific collection of clinical, laboratory, and brain imaging data helping to unveil mechanisms of increased risk of stroke for women. Because stroke is a rare event among younger women, collaborative efforts are needed to identify subgroups of women at particular increased risk. Such collective efforts are also needed to evaluate genetic determinants of stroke in women as well as potential gene-environment interactions.
Acknowledgments
Disclosures
None.
accepted January 12, 2009.
References
1. Bousser MG. Stroke in women: the 1997 Paul Dudley White International Lecture. Circulation. 1999; 99: 463–467.
2. Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association council on stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Circulation. 2006; 113: e409–e449.
3. American Heart Association. Heart Disease and Stroke Statistics. Dallas: AHA; 2008.
4. Struijs JN, van Genugten ML, Evers SM, Ament AJ, Baan CA, van den Bos GA. Modeling the future burden of stroke in The Netherlands: impact of aging, smoking, and hypertension. Stroke. 2005; 36: 1648–1655.
5. Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G, Khatiwoda A, Lisabeth L. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol. 2008; 7: 915–926.[CrossRef][Medline] [Order article via Infotrieve]
6. Sex matters for stroke. Lancet Neurol. 2008; 7: 859.[CrossRef][Medline] [Order article via Infotrieve]
7. Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Ann Intern Med. 2000; 133: 933–941.
8. Viscoli CM, Brass LM, Kernan WN, Sarrel PM, Suissa S, Horwitz RI. Estrogen therapy and risk of cognitive decline: results from the Women’s Estrogen for Stroke Trial (WEST). Am J Obstet Gynecol. 2005; 192: 387–393.[CrossRef][Medline] [Order article via Infotrieve]
9. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, Kotchen T, Curb JD, Black H, Rossouw JE, Aragaki A, Safford M, Stein E, Laowattana S, Mysiw WJ. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA. 2003; 289: 2673–2684.
10. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004; 291: 1701–1712.
11. Qureshi AI, Giles WH, Croft JB, Stern BJ. Number of pregnancies and risk for stroke and stroke subtypes. Arch Neurol. 1997; 54: 203–206.
12. Kittner SJ, Stern BJ, Feeser BR, Hebel R, Nagey DA, Buchholz DW, Earley CJ, Johnson CJ, Macko RF, Sloan MA, Wityk RJ, Wozniak MA. Pregnancy and the risk of stroke. N Engl J Med. 1996; 335: 768–774.
13. Bushnell CD, Jamison M, James AH. Migraine during pregnancies linked to stroke and vascular disease: a United States population-based study. BMJ. In press.
14. Gillum LA, Mamidipudi SK, Johnston SC. Ischemic stroke risk with oral contraceptives: a meta-analysis. JAMA. 2000; 284: 72–78.
15. Tzourio C, Bousser MG. Migraine: a risk factor for ischemic stroke in young women. Stroke. 1997; 28: 2569–2570.[Medline] [Order article via Infotrieve]
16. Carolei A, Marini C, De Matteis G. History of migraine and risk of cerebral ischaemia in young adults. The Italian National Research Council Study Group on stroke in the young. Lancet. 1996; 347: 1503–1506.[Medline] [Order article via Infotrieve]
17. MacClellan LR, Giles WH, Cole J, Wozniak MA, Stern B, Mitchell B, Kittner SJ. Probable migraine with visual aura and risk of ischemic stroke: the Stroke Prevention in Young Women Study. Stroke. 2007; 38: 2438–2445.
18. Kurth T, Schurks M, Logroscino G, Gaziano JM, Buring JE. Migraine, vascular risk, and cardiovascular events in women: prospective cohort study. BMJ. 2008; 337: a636.
19. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005; 352: 1293–1304.
20. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002; 324: 71–86.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||