Advertisement

Cerebral Circulation in Men and Women

  • Aurangzeb Memon
  • Louise D. McCullough
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1065)

Abstract

Despite several advancements in stroke care, disparities continue to exist with regard to sex differences in cerebrovascular disease. These sex differences are due to a combination of several factors, many of which are unique to the female sex. Some of these unique factors, such as pregnancy and menopause, are related to hormonal changes seen throughout the female life cycle. Hormonal fluctuations, which impact the protective effects of the female sex hormones, can be induced by the use of hormonal contraception. Other risk factors, although present in both sexes, have a higher prevalence in elderly females, such as atrial fibrillation leading to cardioembolic strokes. Similarly, differences in premorbid modified Rankin Scale have an impact on the differences in stroke outcome between the two sexes. Clinical research aimed toward highlighting potential causes of these disparities has shown important differences in the calibers of blood vessels in the cerebral circulation between the two sexes, whereas basic science research has shown differences in circulating endothelial progenitor cell pools between males and females, with higher levels being more protective. With the increasing awareness of these sex differences, future research is being geared toward gender-specific modes of therapy, focusing on the molecular level, as well as the individual patient.

Keywords

Migrainous infarct Cerebral stroke Cardioembolic stroke Modified Rankin Scale Cerebral circulation Sex-specific analysis Barthel index Neuroimaging Pregnancy Atrial fibrillation Menopause Preeclampsia 

References

  1. 1.
  2. 2.
    Mackay J, Mensah G. The atlas of heart disease and stroke. Geneva: World Health Organization; 2004.Google Scholar
  3. 3.
    Giralt D, Domingues-Montanari S, Mendioroz M, Ortega L, Maisterra O, Perea-Gainza M, Delgado P, Rosell A, Montaner J. The gender gap in stroke: a meta-analysis. Acta Neurol Scand. 2012;125(2):83–90. https://doi.org/10.1111/j.1600-0404.2011.01514.x.CrossRefPubMedGoogle Scholar
  4. 4.
    Niewada M, Kobayashi A, Sandercock PA, Kaminski B, Czlonkowska A. Influence of gender on baseline features and clinical outcomes among 17,370 patients with confirmed ischaemic stroke in the international stroke trial. Neuroepidemiology. 2005;24:123–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Roquer J, Campello AR, Gomis M. Sex differences in first ever acute stroke. Stroke. 2003;34:1581–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Holroyd-Leduc JM, Kapral MK, Austin PC, Tu JV. Sex differences and similarities in the management and outcome of stroke patients. Stroke. 2000;31:1833–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Kapral MK, Fang J, Hill MD, Silver F, Richards J, Jaigobin C, Cheung AM. Sex differences in stroke care and outcomes: results from the Registry of the Canadian Stroke Network. Stroke. 2005;36:809–14.CrossRefPubMedGoogle Scholar
  8. 8.
    Reid JM, Dai D, Gubitz GJ, Kapral MK, Christian C, Phillips SJ. Gender differences in stroke examined in a 10-year cohort of patients admitted to a Canadian teaching hospital. Stroke. 2008;39:1090–5.CrossRefPubMedGoogle Scholar
  9. 9.
    Glader EL, Stegmayr B, Norrving B, Terent A, Hulter-Asberg K, Wester PO, Asplund K. Sex differences in management and outcome after stroke: a Swedish national perspective. Stroke. 2003;34:1970–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Gargano JW, Reeves MJ. Sex differences in stroke recovery and stroke-specific quality of life: results from a statewide stroke registry. Stroke. 2007;38:2541–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Renoux C, Rothwell PM, et al. Confounding by pre-morbid functional status in studies of apparent sex differences in severity and outcome of stroke. Stroke. 2017;48:2731–8. https://doi.org/10.1161/STROKEAHA.117.018187.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Phan HT, Gall S, et al. Sex differences in long-term mortality after stroke in the INSTRUCT (INternational STRoke oUtComes sTudy): a meta-analysis of individual participant data. Circ Cardiovasc Qual Outcomes. 2017;10:e003436.CrossRefPubMedGoogle Scholar
  13. 13.
    Gall SL, Thrift AG, et al. Sex differences in presentation, severity, and management of stroke in a population based study. Neurology. 2010;74:974–81.CrossRefGoogle Scholar
  14. 14.
    Reeves M, Bhatt A, Jajou P, Brown M, Lisabeth L. Sex differences in the use of intravenous rt-PA thrombolysis treatment for acute ischemic stroke, a meta-analysis. Stroke. 2009;40:1743–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Fredwall M, Sternberg S, Blackhurst D, Lee A, Leacock R, Nathaniel TI. Gender differences in exclusion criteria for recombinant tissue-type plasminogen activator. J Stroke Cerebrovasc Dis. 2016;25:2569–74.CrossRefPubMedGoogle Scholar
  16. 16.
    Savitz SI, Schlaug G, Caplan L, Selim M. Arterial occlusive lesions recanalize more frequently in women than in men after intravenous tissue plasminogen activator administration for acute stroke. Stroke. 2005;36:1447–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Asdaghi N, Romano JG, Wang K, Ciliberti-Vargas MA, Koch S, Gardener H, Dong C, Rose DZ, Waddy SP, Robichaux M, Garcia EJ, Gonzalez-Sanchez JA, Burgin WS, Sacco RL, Rundek T. Sex disparities in ischemic stroke care: FL-PR CReSD study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). Stroke. 2016;47(10):2618–26.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, Khalessi AA, Levy EI, Palesch YY, Prabhakaran S, Saposnik G, Saver JL, Smith EE, American Heart Association Stroke Council and Council on Epidemiology and Prevention. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581–641.CrossRefPubMedGoogle Scholar
  19. 19.
    Labiche LA, Chan W, Saldin KR, Morgenstern LB. Sex and acute stroke presentation. Ann Emerg Med. 2002;40:453–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Acciarresi M, De Luca P, Caso V, Agnelli G, D’Amore C, Alberti A, Venti M, Paciaroni M. Acute stroke symptoms: do differences exist between sexes? J Stroke Cerebrovasc Dis. 2014;23(10):2928–33.CrossRefPubMedGoogle Scholar
  21. 21.
    Smith MA, Lisabeth LD, Brown DL, Morgenstern LB. Gender comparisons of diagnostic evaluation for ischemic stroke patients. Neurology. 2005;65:855–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Gattringer T, Ferrari J, Knoflach M, Seyfang L, Horner S, Niederkorn K, Culea V, Beitzke M, Lang W, Enzinger C, Fazekas F. Sex-related differences of acute stroke unit care: results from the Austrian stroke unit registry. Stroke. 2014;45(6):1632–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Vagal A, Sanelli P, Sucharew H, Alwell KA, Khoury JC, Khatri P, Woo D, Flaherty M, Kissela BM, Adeoye O, Ferioli S, De Los Rios La Rosa F, Martini S, Mackey J, Kleindorfer D. Age, sex, and racial differences in neuroimaging use in acute stroke: a population based study. AJNR Am J Neuroradiol. 2017;38:1905–10. https://doi.org/10.3174/ajnr.A5340.CrossRefPubMedGoogle Scholar
  24. 24.
    Turaj W, Slowik A, Wnuk M, Szczudlik A. Gender-related differences in diagnostic evaluation and outcome of ischemic stroke in Poland. Stroke. 2009;40(3):980–2.CrossRefPubMedGoogle Scholar
  25. 25.
    Madisen TE, Choo EK, Seigel TA, Palms D, Silver B. Lack of gender disparities in emergency department triage of acute stroke patients. West J Emerg Med. 2015;16(1):203–9.CrossRefGoogle Scholar
  26. 26.
    Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Camm AJ, Lip GY, De Caterina R, et al. Focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33:2719–47.CrossRefPubMedGoogle Scholar
  28. 28.
    Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, Hart RG. Prevalence, age distribution, and gender of patients with atrial fibrillation. Analysis and implications. Arch Intern Med. 1995;155:469–73.CrossRefPubMedGoogle Scholar
  29. 29.
    Madias C, Trohman RG. The link between atrial fibrillation and stroke in women. Women’s Health. 2011;7:375–82.PubMedGoogle Scholar
  30. 30.
    Wagstaff AJ, Overvad TF, Lip GYH, Lane DA. Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis. QJM, Int J Med. 2014;107(12):955–67.CrossRefGoogle Scholar
  31. 31.
    Camm AJ, Accetta G, Al Mahmeed W, for the GARFIELD-AF Investigators, et al. Impact of gender on event rates at 1 year in patients with newly diagnosed non-valvular atrial fibrillation: contemporary perspective from the GARFIELD-AF registry. BMJ Open. 2017;7:e014579. https://doi.org/10.1136/bmjopen-2016-014579.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Cove CL, Albert CM, Andreotti F, Badimon L, van Gelder IC, Hylek EM. Female sex as an independent risk factor for stroke in atrial fibrillation: possible mechanisms. Thromb Haemost. 2014;111:385–91.CrossRefPubMedGoogle Scholar
  33. 33.
    Conway DS, Heeringa J, van Der Kuip DA, Chin BS, Hofman A, Witteman JC, et al. Atrial fibrillation and the prothrombotic state in the elderly: the Rotterdam Study. Stroke. 2003;34:413–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Wieberdink RG, van Schie MC, Koudstaal PJ, Hofman A, Witteman JC, de Maat MP, et al. High von Willebrand factor levels increase the risk of stroke: the Rotterdam Study. Stroke. 2010;41:2151–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Sullivan R, Zhang J, Zamba G, Lip GYH, Olshansky B. Relation of gender-specific risk of ischemic stroke in patients with atrial fibrillation to differences in warfarin anticoagulation control (from AFFIRM). Am J Cardiol. 2012;110:1799–802.CrossRefPubMedGoogle Scholar
  36. 36.
    Pancholy SB, Sharma PS, Pancholy DS, et al. Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants. Am J Cardiol. 2014;113:485–90.CrossRefPubMedGoogle Scholar
  37. 37.
    Shantha GPS, Bhave PD, Girotra S, Hodgson-Zingman D, Mazur A, Giudici M, Chrischilles E, Sarrazin MSV. Sex-specific comparative effectiveness of oral anticoagulants in elderly patients with newly diagnosed atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2017;10:e003418.CrossRefPubMedCentralGoogle Scholar
  38. 38.
    Schnabel RB, Pecen L, Ojeda FM, et al. Heart. 2017. https://doi.org/10.1136/heartjnl-2016-310406.
  39. 39.
    Gall SL, Donnan G, Dewey HM, Macdonell R, Sturm J, Gilligan A, Srikanth V, Thrift AG. Sex differences in presentation, severity, and management of stroke in a population based study. Neurology. 2010;74:975–81.CrossRefPubMedGoogle Scholar
  40. 40.
    Peters SA, Huxley RR, Woodward M. Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes. Lancet. 2014;383(9933):1973–80.CrossRefPubMedGoogle Scholar
  41. 41.
    Policardo L, Seghieri G, Francesconi P, Anichini R, Franconi F. Gender difference in diabetes-associated risk of first-ever and recurrent ischemic stroke. J Diabetes Complicat. 2015;29:713–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Towfighi A, Saver JL, Engelhardt R, Ovbiagele. A midlife stroke surge among women in the United States. Neurology. 2007;69(20):1898–904.CrossRefPubMedGoogle Scholar
  43. 43.
    Davis SR, Castelo-Branco C, Chedraui P, Lumsden MA, Nappi RE, Shah D, Villaseca P. Writing Group of the International Menopause Society for World Menopause Day 2012: understanding weight gain at menopause. Climacteric. 2012;15(5):419–29.CrossRefPubMedGoogle Scholar
  44. 44.
    Mauvais-Jarvis F. Sex differences in metabolic homeostasis, diabetes, and obesity. Biol Sex Differ. 2015;6:14.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32(9):1431–7.CrossRefGoogle Scholar
  46. 46.
    Rodríguez-Campello A, Jiménez-Conde J, Ois Á, Cuadrado-Godia E, Giralt-Steinhauer E, Vivanco RM, Soriano-Tárraga C, Subirana I, Muñoz D, Gómez-González A, Puig-Pijoan A, Roquer J. Sex-related differences in abdominal obesity impact on ischemic stroke risk. Eur J Neurol. 2017;24(2):397–403.CrossRefPubMedGoogle Scholar
  47. 47.
    Kuklina EV, Tong X, Bansil P, George MG, Callaghan WM. Trends in pregnancy hospitalizations that included a stroke in the United States from 1994 to 2007: reasons for concern? Stroke. 2011;42:2564–70.CrossRefPubMedGoogle Scholar
  48. 48.
    James AH, Bushnell CD, Jamison MG, et al. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol. 2005;106:509–16.CrossRefPubMedGoogle Scholar
  49. 49.
    Lanska DJ, Kryscio RJ. Stroke and intracranial venous thrombosis during pregnancy and puerperium. Neurology. 1998;51:1622–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke. 2000;31:1274–82.CrossRefPubMedGoogle Scholar
  51. 51.
    Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJ. Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension. 2009;53:944–51.CrossRefPubMedGoogle Scholar
  52. 52.
    McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J. 2008;156:918–30.CrossRefPubMedGoogle Scholar
  53. 53.
    Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the American Heart Association. Circulation. 2011;123:1243–62.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ritzel RM, Patel AR, Spychala M, Verma R, Crapser J, Koellhoffer EC, Schrecengost A, Jellison ER, Zhu L, Venna VR, McCullough LD. Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk. Proc Natl Acad Sci U S A. 2017;114(28):E5673–82.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Racicot K, Kwon JY, Aldo P, Silasi M, Mor G. Understanding the complexity of the immune system during pregnancy. Am J Reprod Immunol. 2014;72(2):107–16.CrossRefPubMedGoogle Scholar
  56. 56.
    Falick Michaeli T, Bergman Y, Gielchinsky Y. Rejuvenating effect of pregnancy on the mother. Fertil Steril. 2015;103(5):1125–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Jeanty C, Derderian SC, Mackenzie TC. Maternal-fetal cellular trafficking: clinical implications and consequences. Curr Opin Pediatr. 2014;26(3):377–82.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Dutta P, Burlingham WJ. Microchimerism: tolerance vs. sensitization. Curr Opin Organ Transplant. 2011;16(4):359–65.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Mahmood U, O’Donoghue K. Microchimeric fetal cells play a role in maternal wound healing after pregnancy. Chimerism. 2014;5(2):40–52.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Urrutia P, Rachel R. Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis. Obstet Gynecol. 2013;122:380–9.CrossRefGoogle Scholar
  61. 61.
    Kurth T, Slomke MA, Kase CS, et al. Migraine, headache, and the risk of stroke in women: a prospective study. Neurology. 2005;64:1020–6.CrossRefPubMedGoogle Scholar
  62. 62.
    Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang-Levine J, Li Y, Feng M, Dustin L, Kono N, Stanczyk FZ, Selzer RH, Azen SP, for the ELITE Research Group. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374:1221–31.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Manson JE, Allison MA, Rossouw JE, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356:2591–602.CrossRefPubMedGoogle Scholar
  64. 64.
    Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Køber L, Jensen JB. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409. https://doi.org/10.1136/bmj.e6409.CrossRefPubMedGoogle Scholar
  65. 65.
    O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK, Group. ftCHSCR. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999;340:14–22.CrossRefPubMedGoogle Scholar
  66. 66.
    Corretti MC, Anderson TJ, Benjamin EJ. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardiol. 2002;39:257–65.CrossRefPubMedGoogle Scholar
  67. 67.
    Fadini GP, de Kreutzenberg S, Albiero M, Coracina A, Pagnin E, Baesso E, Cignarella A, Bolego C, Plebani M, Nardelli GB, Sartore S, Agostini C, Avogaro A. Gender differences in endothelial progenitor cells and cardiovascular risk profile: the role of female estrogens. Arterioscler Thromb Vasc Biol. 2008;28:997–1004.CrossRefPubMedGoogle Scholar
  68. 68.
    Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A. Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J. 2006;27:2247–55.CrossRefPubMedGoogle Scholar
  69. 69.
    Hayashi S, Yamada K, Esaki T, et al. Estrogen increases endothelial nitric oxide by a receptor-mediated system. Biochem Biophys Res Commun. 1995;214:847–55.CrossRefPubMedGoogle Scholar
  70. 70.
    Weiner CP, Lizasoain I, Baylis SA, et al. Induction of calcium- dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci U S A. 1994;91:5212–6.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Miller AA, Drummond GR, Sobey CG. Novel isoforms of NADPH oxidase in cerebral vascular control. Pharmacol Ther. 2006;111:928–48.CrossRefPubMedGoogle Scholar
  72. 72.
    Miller AA, Drummond GR, Mast AE, Schmidt HHHW, Sobey CG. Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation: role of estrogen. Stroke. 2007;38:2142–9.CrossRefGoogle Scholar
  73. 73.
    Davis CM, Siler DA, Alkayed NJEDHF. In the brain: influence of sex, vessel size and disease state. Women’s Health (Lond Engl). 2011;7(3):293–303.CrossRefGoogle Scholar
  74. 74.
    Stefani MA, Schneider FL, Marrone ACH, Severino AG. Influence of the gender on cerebral vascular diameters observed during the magnetic resonance angiographic examination of Willis circle. Braz Arch Biol Technol. 2013;56:1.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyProvidence HospitalMobileUSA
  2. 2.Huffington Distinguished Chair of NeurologyHoustonUSA
  3. 3.Memorial Herman Hospital – TMC, HoustonHoustonUSA
  4. 4.The University of Texas Health Science CenterHoustonUSA

Personalised recommendations