Skip to main content
Top
Published in: Translational Stroke Research 3/2018

01-06-2018 | Original Article

Factors Mediating Outcome After Stroke: Gender, Thrombolysis, and Their Interaction

Authors: Seung-Jae Lee, Sung Hyuk Heo, Walter T. Ambrosius, Cheryl D. Bushnell

Published in: Translational Stroke Research | Issue 3/2018

Login to get access

Abstract

Several studies, but not all, have shown that women benefit more from intravenous thrombolysis than men; few have accounted for pre-stroke mobility. Our aim was to determine whether there was an interaction between gender and thrombolysis treatment in 3-month modified Rankin Scale (mRS) score, after adjusting for pre-stroke mobility. We retrospectively reviewed medical records of 1390 consecutive ischemic stroke patients admitted between October 2012 and July 2015. The 3-month mRS was obtained from clinic visits. Thrombolysis-by-gender interaction was evaluated in univariate and multivariate analyses using ordinal logistic (“shift”) regression with the full mRS range from 0 to 6 as the dependent variable. We included 926 (456 women and 470 men) patients with follow-up. Women were older (mean age 68.1 vs 65.8 years, P = 0.013), less likely to be treated with thrombolysis (15.6 vs 24.0%, P = 0.002), less often discharged to home (49.1 vs 59.6%, P = 0.001), and more likely to use ambulation aids pre-stroke (13.6 vs 8.5%, P = 0.014).Women had worse outcomes than men in those not treated with thrombolysis (mRS ≥ 3: 55.1 vs 40.1%, P < 0.001). In those who received thrombolysis, there were no gender differences (47.9 vs 50.4%, P = 0.736). In multivariable modeling, there was a significant gender-treatment interaction (P < 0.001), after adjustment for gender, pre-stroke ambulation aid use, age, age-by-gender interaction, initial stroke severity, diabetes, heart failure, and prior stroke. Our results show that women benefit from thrombolysis more than men, and the thrombolysis-by-gender interaction persists after adjustment for pre-stroke mobility impairment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G, et al. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol. 2008;7:915–26.CrossRefPubMedPubMedCentral Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G, et al. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. Lancet Neurol. 2008;7:915–26.CrossRefPubMedPubMedCentral
2.
go back to reference De Silva DA, Ebinger M, Davis SM. Gender issues in acute stroke thrombolysis. J Clin Neurosci. 2009;16:501–4.CrossRefPubMed De Silva DA, Ebinger M, Davis SM. Gender issues in acute stroke thrombolysis. J Clin Neurosci. 2009;16:501–4.CrossRefPubMed
3.
go back to reference Bushnell CD, Reeves MJ, Zhao X, Pan W, Prvu-Bettger J, Zimmer L, et al. Sex differences in quality of life after ischemic stroke. Neurology. 2014;82:922–31.CrossRefPubMedPubMedCentral Bushnell CD, Reeves MJ, Zhao X, Pan W, Prvu-Bettger J, Zimmer L, et al. Sex differences in quality of life after ischemic stroke. Neurology. 2014;82:922–31.CrossRefPubMedPubMedCentral
4.
go back to reference Bettger JP, Zhao X, Bushnell C, Zimmer L, Pan W, Williams LS, et al. The association between socioeconomic status and disability after stroke: findings from the adherence eValuation after ischemic stroke longitudinal (AVAIL) registry. BMC Public Health. 2014;14:281.CrossRefPubMedPubMedCentral Bettger JP, Zhao X, Bushnell C, Zimmer L, Pan W, Williams LS, et al. The association between socioeconomic status and disability after stroke: findings from the adherence eValuation after ischemic stroke longitudinal (AVAIL) registry. BMC Public Health. 2014;14:281.CrossRefPubMedPubMedCentral
5.
go back to reference Kapral MK, Fang J, Hill MD, Silver F, Richards J, Jaigobin C, et al. Sex differences in stroke care and outcomes: results from the registry of the Canadian stroke network. Stroke. 2005;36:809–14.CrossRefPubMed Kapral MK, Fang J, Hill MD, Silver F, Richards J, Jaigobin C, et al. Sex differences in stroke care and outcomes: results from the registry of the Canadian stroke network. Stroke. 2005;36:809–14.CrossRefPubMed
6.
go back to reference Glader EL, Stegmayr B, Norrving B, Terént A, Hulter-Asberg K, Wester PO, et al. Sex differences in management and outcome after stroke: a Swedish national perspective. Stroke. 2003;34:1970–5.CrossRefPubMed Glader EL, Stegmayr B, Norrving B, Terént A, Hulter-Asberg K, Wester PO, et al. Sex differences in management and outcome after stroke: a Swedish national perspective. Stroke. 2003;34:1970–5.CrossRefPubMed
7.
go back to reference Foerch C, Misselwitz B, Humpich M, Steinmetz H, Neumann-Haefelin T, Sitzer M, et al. Sex disparity in the access of elderly patients to acute stroke care. Stroke. 2007;38:2123–6.CrossRefPubMed Foerch C, Misselwitz B, Humpich M, Steinmetz H, Neumann-Haefelin T, Sitzer M, et al. Sex disparity in the access of elderly patients to acute stroke care. Stroke. 2007;38:2123–6.CrossRefPubMed
9.
go back to reference Roquer J, Campello AR, Gomis M. Sex differences in first-ever acute stroke. Stroke. 2003;34:1581–5.CrossRefPubMed Roquer J, Campello AR, Gomis M. Sex differences in first-ever acute stroke. Stroke. 2003;34:1581–5.CrossRefPubMed
10.
go back to reference Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001;32:2735–40.CrossRefPubMed Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001;32:2735–40.CrossRefPubMed
11.
go back to reference Gray LJ, Sprigg N, Bath PM, Boysen G, De Deyn PP, Leys D, et al. Sex differences in quality of life in stroke survivors: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST). Stroke. 2007;38:2960–4.CrossRefPubMed Gray LJ, Sprigg N, Bath PM, Boysen G, De Deyn PP, Leys D, et al. Sex differences in quality of life in stroke survivors: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST). Stroke. 2007;38:2960–4.CrossRefPubMed
12.
go back to reference Gattringer T, Ferrari J, Knoflach M, Seyfang L, Horner S, Niederkorn K, et al. Sex-related differences of acute stroke unit care: results from the Austrian stroke unit registry. Stroke. 2014;45:1632–8.CrossRefPubMed Gattringer T, Ferrari J, Knoflach M, Seyfang L, Horner S, Niederkorn K, et al. Sex-related differences of acute stroke unit care: results from the Austrian stroke unit registry. Stroke. 2014;45:1632–8.CrossRefPubMed
13.
go back to reference Paradiso S, Robinson RG. Gender differences in poststroke depression. J Neuropsychiatry Clin Neurosci. 1998;10:41–7.CrossRefPubMed Paradiso S, Robinson RG. Gender differences in poststroke depression. J Neuropsychiatry Clin Neurosci. 1998;10:41–7.CrossRefPubMed
14.
go back to reference Shimoda K, Robinson RG. Effects of anxiety disorder on impairment and recovery from stroke. J Neuropsychiatry Clin Neurosci. 1998;10:34–40.CrossRefPubMed Shimoda K, Robinson RG. Effects of anxiety disorder on impairment and recovery from stroke. J Neuropsychiatry Clin Neurosci. 1998;10:34–40.CrossRefPubMed
15.
go back to reference Kent DM, Buchan AM, Hill MD. The gender effect in stroke thrombolysis: of CASES, controls, and treatment-effect modification. Neurology. 2008;71:1080–3.CrossRefPubMed Kent DM, Buchan AM, Hill MD. The gender effect in stroke thrombolysis: of CASES, controls, and treatment-effect modification. Neurology. 2008;71:1080–3.CrossRefPubMed
16.
go back to reference Lorenzano S, Ahmed N, Falcou A, Mikulik R, Tatlisumak T, Roffe C, et al. Does sex influence the response to intravenous thrombolysis in ischemic stroke?: answers from safe implementation of treatments in Stroke-International Stroke Thrombolysis Register. Stroke. 2013;44:3401–6.CrossRefPubMed Lorenzano S, Ahmed N, Falcou A, Mikulik R, Tatlisumak T, Roffe C, et al. Does sex influence the response to intravenous thrombolysis in ischemic stroke?: answers from safe implementation of treatments in Stroke-International Stroke Thrombolysis Register. Stroke. 2013;44:3401–6.CrossRefPubMed
17.
go back to reference Förster A, Gass A, Kern R, Wolf ME, Ottomeyer C, Zohsel K, et al. Gender differences in acute ischemic stroke: etiology, stroke patterns and response to thrombolysis. Stroke. 2009;40:2428–32.CrossRefPubMed Förster A, Gass A, Kern R, Wolf ME, Ottomeyer C, Zohsel K, et al. Gender differences in acute ischemic stroke: etiology, stroke patterns and response to thrombolysis. Stroke. 2009;40:2428–32.CrossRefPubMed
18.
go back to reference Meseguer E, Mazighi M, Labreuche J, Arnaiz C, Cabrejo L, Slaoui T, et al. Outcomes of intravenous recombinant tissue plasminogen activator therapy according to gender: a clinical registry study and systematic review. Stroke. 2009;40:2104–10.CrossRefPubMed Meseguer E, Mazighi M, Labreuche J, Arnaiz C, Cabrejo L, Slaoui T, et al. Outcomes of intravenous recombinant tissue plasminogen activator therapy according to gender: a clinical registry study and systematic review. Stroke. 2009;40:2104–10.CrossRefPubMed
19.
go back to reference Jovanović DR, Beslać-Bumbasirević L, Budimkić M, Pekmezović T, Zivković M, Kostić VS, et al. Do women benefit more from systemic thrombolysis in acute ischemic stroke? A Serbian experience with thrombolysis in ischemic stroke (SETIS) study. Clin Neurol Neurosurg. 2009;111:729–32.CrossRefPubMed Jovanović DR, Beslać-Bumbasirević L, Budimkić M, Pekmezović T, Zivković M, Kostić VS, et al. Do women benefit more from systemic thrombolysis in acute ischemic stroke? A Serbian experience with thrombolysis in ischemic stroke (SETIS) study. Clin Neurol Neurosurg. 2009;111:729–32.CrossRefPubMed
20.
go back to reference Elkind MS, Prabhakaran S, Pittman J, Koroshetz W, Jacoby M, Johnston KC, et al. Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke. Neurology. 2007;68:842–8.CrossRefPubMed Elkind MS, Prabhakaran S, Pittman J, Koroshetz W, Jacoby M, Johnston KC, et al. Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke. Neurology. 2007;68:842–8.CrossRefPubMed
21.
go back to reference Al-hussain F, Hussain MS, Molina C, Uchino K, Shuaib A, Demchuk AM, et al. Does the sex of acute stroke patients influence the effectiveness of rt-PA? BMC Neurol. 2014;14:60.CrossRefPubMedPubMedCentral Al-hussain F, Hussain MS, Molina C, Uchino K, Shuaib A, Demchuk AM, et al. Does the sex of acute stroke patients influence the effectiveness of rt-PA? BMC Neurol. 2014;14:60.CrossRefPubMedPubMedCentral
22.
go back to reference Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007;369:275–82.CrossRefPubMed Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007;369:275–82.CrossRefPubMed
23.
go back to reference The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–7.CrossRef The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–7.CrossRef
24.
go back to reference Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998;352:1245–1251. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, Larrue V, Bluhmki E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas P. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998;352:1245–1251.
25.
go back to reference Shobha N, Sylaja PN, Kapral MK, Fang J, Hill MD, Investigators of the Registry of the Canadian Stroke Network. Differences in stroke outcome based on sex. Neurology. 2010;74:767–71.CrossRefPubMedPubMedCentral Shobha N, Sylaja PN, Kapral MK, Fang J, Hill MD, Investigators of the Registry of the Canadian Stroke Network. Differences in stroke outcome based on sex. Neurology. 2010;74:767–71.CrossRefPubMedPubMedCentral
26.
27.
go back to reference Saposnik G, Di Legge S, Webster F, Hachinski V. Predictors of major neurologic improvement after thrombolysis in acute stroke. Neurology. 2005;65:1169–74.CrossRefPubMed Saposnik G, Di Legge S, Webster F, Hachinski V. Predictors of major neurologic improvement after thrombolysis in acute stroke. Neurology. 2005;65:1169–74.CrossRefPubMed
28.
go back to reference Lasek-Bal A, Puz P, Kazibutowska Z. Efficacy and safety assessment of alteplase in the treatment of stroke—gender differences. Neurol Res. 2014;36:851–6.CrossRefPubMed Lasek-Bal A, Puz P, Kazibutowska Z. Efficacy and safety assessment of alteplase in the treatment of stroke—gender differences. Neurol Res. 2014;36:851–6.CrossRefPubMed
29.
go back to reference Hametner C, MacIsaac RL, Kellert L, Abdul-Rahim AH, Ringleb PA, Lees KR, et al. Sex and stroke in thrombolyzed patients and controls. Stroke. 2017;48:367–74.CrossRefPubMed Hametner C, MacIsaac RL, Kellert L, Abdul-Rahim AH, Ringleb PA, Lees KR, et al. Sex and stroke in thrombolyzed patients and controls. Stroke. 2017;48:367–74.CrossRefPubMed
30.
go back to reference Spaander FH, Zinkstok SM, Baharoglu IM, Gensicke H, Polymeris A, Traenka C, Hametner C, Ringleb P, Curtze S, Martinez-Majander N, Aarnio K, Nolte CH, Scheitz JF, Leys D, Hochart A, Padjen V, Kägi G, Pezzini A, Michel P, Bill O, Zini A, Engelter ST, Nederkoorn PJ; Thrombolysis in Ischemic Stroke Patients Collaborators (TrISP). Sex differences and functional outcome after intravenous thrombolysis revision. Stroke. 2017 Jan 31. pii: STROKEAHA.116.014739. https://doi.org/10.1161/STROKEAHA.116.014739. Spaander FH, Zinkstok SM, Baharoglu IM, Gensicke H, Polymeris A, Traenka C, Hametner C, Ringleb P, Curtze S, Martinez-Majander N, Aarnio K, Nolte CH, Scheitz JF, Leys D, Hochart A, Padjen V, Kägi G, Pezzini A, Michel P, Bill O, Zini A, Engelter ST, Nederkoorn PJ; Thrombolysis in Ischemic Stroke Patients Collaborators (TrISP). Sex differences and functional outcome after intravenous thrombolysis revision. Stroke. 2017 Jan 31. pii: STROKEAHA.116.014739. https://​doi.​org/​10.​1161/​STROKEAHA.​116.​014739.
31.
go back to reference Reed SD, Cramer SC, Blough DK, Meyer K, Jarvik JG. Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals. Stroke. 2001;32:1832–40.CrossRefPubMed Reed SD, Cramer SC, Blough DK, Meyer K, Jarvik JG. Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals. Stroke. 2001;32:1832–40.CrossRefPubMed
32.
go back to reference Reeves MJ, Fonarow GC, Zhao X, Smith EE, Schwamm LH, Get With The Guidelines-Stroke Steering Committee & Investigators. Quality of care in women with ischemic stroke in the GWTG program. Stroke. 2009;40:1127–33.CrossRefPubMed Reeves MJ, Fonarow GC, Zhao X, Smith EE, Schwamm LH, Get With The Guidelines-Stroke Steering Committee & Investigators. Quality of care in women with ischemic stroke in the GWTG program. Stroke. 2009;40:1127–33.CrossRefPubMed
33.
go back to reference Reeves MJ, Wilkins T, Lisabeth LD, Schwamm LH. Thrombolysis treatment for acute stroke: issues of efficacy and utilization in women. Womens Health (LondEngl). 2011;7:383–90.CrossRef Reeves MJ, Wilkins T, Lisabeth LD, Schwamm LH. Thrombolysis treatment for acute stroke: issues of efficacy and utilization in women. Womens Health (LondEngl). 2011;7:383–90.CrossRef
34.
go back to reference Kapral MK, Devon J, Winter AL, Wang J, Peters A, Bondy SJ. Gender differences in stroke care decision-making. Med Care. 2006;44:70–80.CrossRefPubMed Kapral MK, Devon J, Winter AL, Wang J, Peters A, Bondy SJ. Gender differences in stroke care decision-making. Med Care. 2006;44:70–80.CrossRefPubMed
Metadata
Title
Factors Mediating Outcome After Stroke: Gender, Thrombolysis, and Their Interaction
Authors
Seung-Jae Lee
Sung Hyuk Heo
Walter T. Ambrosius
Cheryl D. Bushnell
Publication date
01-06-2018
Publisher
Springer US
Published in
Translational Stroke Research / Issue 3/2018
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-017-0579-6

Other articles of this Issue 3/2018

Translational Stroke Research 3/2018 Go to the issue