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Canadian Journal of Cardiology

Sex and Gender Bias as a Mechanistic Determinant of Cardiovascular Disease Outcomes

Published:September 15, 2022DOI:https://doi.org/10.1016/j.cjca.2022.09.009

      Abstract

      Defined as a prejudice either for or against something, biases at the provider, patient, and societal level all contribute to differences in cardiovascular disease recognition and treatment, resulting in outcome disparities between sexes and genders. Provider bias in the under-recognition of female-predominant cardiovascular disease and risks may result in under-screened and under-treated patients. Furthermore, therapies for female-predominant phenotypes including non-obstructive coronary artery disease and heart failure with preserved ejection fraction are less well researched, contributing to under-treated female patients. Conversely, women are less likely to seek urgent medical attention, potentially related to societal bias to put others first, which contributes to diagnostic delays. Furthermore, women are less likely to have discussions around risk factors for coronary artery disease compared to men, partially because they are less likely to consider themselves at risk for heart disease. Provider bias in interpreting a higher number of presenting symptoms, some of which have been labeled as ‘atypical’, can lead to mislabeling presentations as non-cardiovascular. Furthermore, providers may avoid discussions around certain therapies including thrombolysis for stroke, and cardiac resynchronization therapy in heart failure, as it is incorrectly assumed women are not interested in pursuing options deemed more invasive. To mitigate bias, organizations should aim to increase the visibility and involvement of women in research, health promotion, clinical and leadership endeavours. More research needs to be done to identify effective interventions to mitigate sex and gender bias and the resultant cardiovascular outcome discrepancies.

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      References

        • Clayton J.A.
        Studying both sexes: a guiding principle for biomedicine.
        FASEB J. 2016; 30: 519-524
        • Tannenbaum C.
        • et al.
        Evaluating sex as a biological variable in preclinical research: the devil in the details.
        Biol Sex Differ. 2016; 7: 13
        • Johnson J.L.
        • Greaves L.
        • Repta R.
        Better science with sex and gender: Facilitating the use of a sex and gender-based analysis in health research.
        Int J Equity Health. 2009; 8: 14
        • Norris C.M.
        • et al.
        The Contribution of Gender to Apparent Sex Differences in Health Status Among Patients with Coronary Artery Disease.
        J Womens Health (Larchmt). 2017; 26: 50-57
        • Tannenbaum C.
        • Greaves L.
        • Graham I.D.
        Why sex and gender matter in implementation research.
        BMC Med Res Methodol. 2016; 16: 145
        • Raparelli V.
        • et al.
        Identification and inclusion of gender factors in retrospective cohort studies: the GOING-FWD framework.
        BMJ Glob Health. 2021; 6
        • Streed C.G.
        • et al.
        Assessing and Addressing Cardiovascular Health in People Who Are Transgender and Gender Diverse: A Scientific Statement From the American Heart Association.
        Circulation. 2021; 144: e136-e148
        • Sullivan K.
        • et al.
        Sex-Specific Differences in Heart Failure: Pathophysiology, Risk Factors, Management, and Outcomes.
        Can J Cardiol. 2021; 37: 560-571
        • Bucholz E.M.
        • et al.
        Editor's Choice-Sex differences in young patients with acute myocardial infarction: A VIRGO study analysis.
        Eur Heart J Acute Cardiovasc Care. 2017; 6: 610-622
        • Colsch R.
        • Lindseth G.
        Unique Stroke Symptoms in Women: A Review.
        J Neurosci Nurs. 2018; 50: 336-342
        • Lichtman J.H.
        • et al.
        Sex Differences in the Presentation and Perception of Symptoms Among Young Patients With Myocardial Infarction: Evidence from the VIRGO Study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients).
        Circulation. 2018; 137: 781-790
        • Norris C.M.
        • et al.
        State of the Science in Women's Cardiovascular Disease: A Canadian Perspective on the Influence of Sex and Gender.
        J Am Heart Assoc. 2020; 9: e015634
        • Jaffer S.
        • et al.
        The Canadian Women’s Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women; Chapter 2: Scope of the Problem.
        CJC Open. 2021; 3: 1-11
      1. Mosca, L., et al., Fifteen-year trends in awareness of heart disease in women: results of a 2012 American Heart Association national survey. Circulation, 2013. 127(11): p. 1254-1263, e1-1263.

      2. Leifheit-Limson, E.C., et al., Sex Differences in Cardiac Risk Factors, Perceived Risk, and Health Care Provider Discussion of Risk and Risk Modification Among Young Patients With Acute Myocardial Infarction: The VIRGO Study. J Am Coll Cardiol, 2015. 66(18): p. 1949-1957.

        • McDonnell L.A.
        • et al.
        Women's Heart Health: Knowledge, Beliefs, and Practices of Canadian Physicians.
        J Womens Health (Larchmt). 2018; 27: 72-82
        • Rhoades D.R.
        • et al.
        Speaking and interruptions during primary care office visits.
        Fam Med. 2001; 33: 528-532
        • Berger J.S.
        • et al.
        Sex differences in mortality following acute coronary syndromes.
        Jama. 2009; 302: 874-882
        • Gupta A.
        • et al.
        Trends in acute myocardial infarction in young patients and differences by sex and race, 2001 to 2010.
        J Am Coll Cardiol. 2014; 64: 337-345
        • Haider A.
        • et al.
        Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome.
        Eur Heart J. 2020; 41: 1328-1336
        • Anand S.S.
        • et al.
        Risk factors for myocardial infarction in women and men: insights from the INTERHEART study.
        Eur Heart J. 2008; 29: 932-940
        • Peters S.A.
        • Huxley R.R.
        • Woodward M.
        Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events.
        Diabetologia. 2014; 57: 1542-1551
        • Arora S.
        • et al.
        Twenty Year Trends and Sex Differences in Young Adults Hospitalized With Acute Myocardial Infarction.
        Circulation. 2019; 139: 1047-1056
        • Peters S.A.E.
        • Woodward M.
        Sex Differences in the Burden and Complications of Diabetes.
        Current Diabetes Reports. 2018; 18: 33
        • Kirkman M.S.
        • et al.
        Determinants of Adherence to Diabetes Medications: Findings From a Large Pharmacy Claims Database.
        Diabetes Care. 2015; 38: 604-609
        • Kretchy I.A.
        • Owusu-Daaku F.T.
        • Danquah S.A.
        Mental health in hypertension: assessing symptoms of anxiety, depression and stress on anti-hypertensive medication adherence.
        International Journal of Mental Health Systems. 2014; 8: 25
        • Tramunt B.
        • et al.
        Sex differences in metabolic regulation and diabetes susceptibility.
        Diabetologia. 2020; 63: 453-461
        • 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
        • Welten S.J.G.C.
        • et al.
        Age at Menopause and Risk of Ischemic and Hemorrhagic Stroke.
        Stroke. 2021; 52: 2583-2591
        • Liang C.
        • et al.
        Infertility, Miscarriage, Stillbirth, and the Risk of Stroke Among Women: A Systematic Review and Meta-Analysis.
        Stroke. 2022; 53: 328-337
        • Brener A.
        • et al.
        Missed opportunities to prevent cardiovascular disease in women with prior preeclampsia.
        BMC Women's Health. 2020; 20: 217
        • Okoth K.
        • et al.
        Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review.
        BMJ. 2020; 371: m3502
        • Pelletier R.
        • et al.
        Sex Versus Gender-Related Characteristics: Which Predicts Outcome After Acute Coronary Syndrome in the Young?.
        J Am Coll Cardiol. 2016; 67: 127-135
        • Möller-Leimkühler A.M.
        Gender differences in cardiovascular disease and comorbid depression.
        Dialogues in Clinical Neuroscience. 2007; 9: 71-83
      3. CDC - appendix B - US SPR - reproductive health. Published January 16, A.J., 2022. https://www.cdc.gov/reproductivehealth/contraception/mmwr/spr/appendixb.html.

        • Black A.
        • et al.
        No. 329-Canadian Contraception Consensus Part 4 of 4 Chapter 9: Combined Hormonal Contraception.
        Journal of Obstetrics and Gynaecology Canada. 2017; 39 (e5): 229-268
        • Tanis B.C.
        • et al.
        Oral Contraceptives and the Risk of Myocardial Infarction.
        New England Journal of Medicine. 2001; 345: 1787-1793
        • Kaminski P.
        • Szpotanska-Sikorska M.
        • Wielgos M.
        Cardiovascular risk and the use of oral contraceptives.
        Neuro Endocrinol Lett. 2013; 34: 587-589
        • Champney K.P.
        • et al.
        The joint contribution of sex, age and type of myocardial infarction on hospital mortality following acute myocardial infarction.
        Heart. 2009; 95: 895-899
        • Canto J.G.
        • et al.
        Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality.
        Jama. 2012; 307: 813-822
      4. Pepine, C.J., Ischemic Heart Disease in Women. Journal of the American College of Cardiology, 2006. 47(3, Supplement): p. S1-S3.

      5. Waheed, N., et al., Sex differences in non-obstructive coronary artery disease. Cardiovasc Res, 2020. 116(4): p. 829-840.

        • Jung R.G.
        • et al.
        Clinical features, sex differences and outcomes of myocardial infarction with nonobstructive coronary arteries: a registry analysis.
        Coron Artery Dis. 2021; 32: 10-16
      6. Martinuk, S. and T. Meyer, The use of positron emission tomography (PET) for cancer care across Canada: Time for a national strategy. Journal of Nuclear Medicine, 2013. 54(supplement 2): p. 1302-1302.

      7. Singh, J.A., et al., Trends in and disparities for acute myocardial infarction: an analysis of Medicare claims data from 1992 to 2010. BMC Med, 2014. 12: p. 190.

        • Mehilli J.
        • Presbitero P.
        Coronary artery disease and acute coronary syndrome in women.
        Heart. 2020; 106: 487-492
        • Pagidipati N.J.
        • Peterson E.D.
        Acute coronary syndromes in women and men.
        Nat Rev Cardiol. 2016; 13: 471-480
        • Weininger D.
        • et al.
        Delays to Hospital Presentation in Women and Men with ST-Segment Elevation Myocardial Infarction: A Multi-Center Analysis of Patients Hospitalized in New York City.
        Ther Clin Risk Manag. 2022; 18: 1-9
        • Wilkinson C.
        • et al.
        Sex differences in quality indicator attainment for myocardial infarction: a nationwide cohort study.
        Heart. 2019; 105: 516-523
        • Chandra N.C.
        • et al.
        Observations of the Treatment of Women in the United States With Myocardial Infarction: A Report From the National Registry of Myocardial Infarction-I.
        Archives of Internal Medicine. 1998; 158: 981-988
        • Daugherty S.L.
        • et al.
        Implicit Gender Bias and the Use of Cardiovascular Tests Among Cardiologists.
        Journal of the American Heart Association. 2017; 6: e006872
        • Smith J.R.
        • et al.
        Sex Differences in Cardiac Rehabilitation Outcomes.
        Circ Res. 2022; 130: 552-565
        • Colella T.J.
        • et al.
        Sex bias in referral of women to outpatient cardiac rehabilitation? A meta-analysis.
        European Journal of Preventive Cardiology. 2020; 22: 423-441
        • Ko D.
        • et al.
        Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis.
        Nat Rev Cardiol. 2016; 13: 321-332
        • Lee E.
        • et al.
        Mortality and causes of death in patients with atrial fibrillation: A nationwide population-based study.
        PLOS ONE. 2018; 13: e0209687
        • Pancholy S.B.
        • 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: 485-490
        • Cochet H.
        • et al.
        Age, atrial fibrillation, and structural heart disease are the main determinants of left atrial fibrosis detected by delayed-enhanced magnetic resonance imaging in a general cardiology population.
        J Cardiovasc Electrophysiol. 2015; 26: 484-492
        • Yoshida K.
        • et al.
        Effect of Sex Differences on the Association Between Stroke Risk and Left Atrial Anatomy or Mechanics in Patients With Atrial Fibrillation.
        Circulation: Cardiovascular Imaging. 2016; 9: e004999
        • Westerman S.
        • Wenger N.
        Gender Differences in Atrial Fibrillation: A Review of Epidemiology, Management, and Outcomes.
        Curr Cardiol Rev. 2019; 15: 136-144
        • Ball J.
        • et al.
        Women Versus Men with Chronic Atrial Fibrillation: Insights from the Standard Versus Atrial Fibrillation spEcific managemenT studY (SAFETY).
        PLOS ONE. 2013; 8e65795
        • Schnabel R.B.
        • et al.
        Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation.
        Heart. 2017; 103: 1024-1030
        • Yong C.M.
        • et al.
        Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation.
        Journal of the American Heart Association. 2020; 9: e015689
        • Forleo G.B.
        • et al.
        Gender-related differences in catheter ablation of atrial fibrillation.
        Europace. 2007; 9: 613-620
        • Carnlöf C.
        • et al.
        Women with atrial fibrillation undergoing pulmonary vein isolation are more symptomatic but improve more in health-related quality of life and symptom burden than men.
        Scandinavian Cardiovascular Journal. 2022; 56: 316-324
        • Lam C.S.P.
        • et al.
        Sex differences in heart failure.
        Eur Heart J. 2019; 40: 3859-3868c
        • Davis M.B.
        • et al.
        Peripartum Cardiomyopathy: JACC State-of-the-Art Review.
        J Am Coll Cardiol. 2020; 75: 207-221
        • McMurray J.J.V.
        • et al.
        Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.
        New England Journal of Medicine. 2019; 381: 1995-2008
        • Nassif M.E.
        • et al.
        Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial.
        Circulation. 2019; 140: 1463-1476
        • Armstrong P.W.
        • et al.
        Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
        New England Journal of Medicine. 2020; 382: 1883-1893
        • Packer M.
        • et al.
        Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.
        New England Journal of Medicine. 2020; 383: 1413-1424
        • Teerlink J.R.
        • et al.
        Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.
        New England Journal of Medicine. 2020; 384: 105-116
        • Solomon S.D.
        • et al.
        Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.
        New England Journal of Medicine. 2019; 381: 1609-1620
        • Anker S.D.
        • et al.
        Empagliflozin in Heart Failure with a Preserved Ejection Fraction.
        New England Journal of Medicine. 2021; 385: 1451-1461
        • Mitchell M.
        Heart Failure with Preserved Ejection Fraction.
        Current Emergency and Hospital Medicine Reports. 2019; 7: 184-188
        • Scott P.E.
        • et al.
        Participation of Women in Clinical Trials Supporting FDA Approval of Cardiovascular Drugs.
        J Am Coll Cardiol. 2018; 71: 1960-1969
        • Sotomi Y.
        • et al.
        Sex Differences in Heart Failure With Preserved Ejection Fraction.
        Journal of the American Heart Association. 2021; 10: e018574
        • Mentzer G.
        • Hsich E.M.
        Heart Failure with Reduced Ejection Fraction in Women: Epidemiology, Outcomes, and Treatment.
        Heart Fail Clin. 2019; 15: 19-27
        • Vitale C.
        • et al.
        Under-representation of elderly and women in clinical trials.
        International Journal of Cardiology. 2017; 232: 216-221
        • O’Neill Z.R.
        • et al.
        Who says “no” to participating in stroke clinical trials and why: an observational study from the Vancouver Stroke Program.
        Trials. 2019; 20: 313
        • Mills E.J.
        • et al.
        Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors.
        Lancet Oncol. 2006; 7: 141-148
        • Borghans L.
        • et al.
        Gender Differences in Risk Aversion and Ambiguity Aversion.
        Journal of the European Economic Association. 2009; 7: 649-658
        • Cordonnier C.
        • et al.
        Stroke in women - from evidence to inequalities.
        Nat Rev Neurol. 2017; 13: 521-532
        • Nielsen M.W.
        • et al.
        One and a half million medical papers reveal a link between author gender and attention to gender and sex analysis.
        Nat Hum Behav. 2017; 1: 791-796
        • Spall H.G.C.V.
        • et al.
        Ending Gender Inequality in Cardiovascular Clinical Trial Leadership.
        Journal of the American College of Cardiology. 2021; 77: 2960-2972
        • Reza N.
        • et al.
        Representation of Women Authors in International Heart Failure Guidelines and Contemporary Clinical Trials.
        Circ Heart Fail. 2020; 13: e006605
        • Whitelaw S.
        • et al.
        Trial characteristics associated with under-enrolment of females in randomized controlled trials of heart failure with reduced ejection fraction: a systematic review.
        Eur J Heart Fail. 2021; 23: 15-24
        • Hernandez A.F.
        • et al.
        Sex and Racial Differences in the Use of Implantable Cardioverter-Defibrillators Among Patients Hospitalized With Heart Failure.
        JAMA. 2007; 298: 1525-1532
        • Mather M.
        • Lighthall N.R.
        Both Risk and Reward are Processed Differently in Decisions Made Under Stress.
        Curr Dir Psychol Sci. 2012; 21: 36-41
        • Rathore S.S.
        • Wang Y.
        • Krumholz H.M.
        Sex-Based Differences in the Effect of Digoxin for the Treatment of Heart Failure.
        New England Journal of Medicine. 2002; 347: 1403-1411
        • Jochmann N.
        • et al.
        Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases.
        Eur Heart J. 2005; 26: 1585-1595
        • Eisenberg E.
        • Di Palo K.E.
        • Pina I.L.
        Sex differences in heart failure.
        Clin Cardiol. 2018; 41: 211-216
        • Bots S.H.
        • et al.
        Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.
        JACC: Heart Failure. 2019; 7: 258-266
        • McMurray J.J.V.
        • et al.
        Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction.
        Circulation. 2020; 141: 338-351
        • Eisenberg E.
        • Di Palo K.E.
        • Piña I.L.
        Sex differences in heart failure.
        Clinical Cardiology. 2018; 41: 211-216
        • Shih M.-L.
        • et al.
        Gender differences? Factors related to quality of life among patients with Heart failure.
        Women & Health. 2020; 60: 382-395
      8. Glikson, M., et al., 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: Developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) With the special contribution of the European Heart Rhythm Association (EHRA). European Heart Journal, 2021. 42(35): p. 3427-3520.

      9. Zusterzeel, R., et al., Cardiac resynchronization therapy in women: US Food and Drug Administration meta-analysis of patient-level data. JAMA Intern Med, 2014. 174(8): p. 1340-1348.

        • Mohamed M.O.
        • et al.
        Sex Disparities in the Choice of Cardiac Resynchronization Therapy Device: An Analysis of Trends, Predictors, and Outcomes.
        Can J Cardiol. 2021; 37: 86-93
        • Daugherty S.L.
        • et al.
        Implicit Gender Bias and the Use of Cardiovascular Tests Among Cardiologists.
        J Am Heart Assoc. 2017; 6
        • Ramirez F.D.
        Sex Differences in Cardiac Resynchronization Therapy Device Implantations and Complications: Tough Questions, Tougher Answers.
        Can J Cardiol. 2021; 37: 14-16
        • Song P.
        • et al.
        Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis.
        The Lancet Global Health. 2019; 7: e1020-e1030
        • Fowkes F.G.
        • et al.
        Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.
        Lancet. 2013; 382: 1329-1340
        • Higgins J.P.
        • Higgins J.A.
        Epidemiology of peripheral arterial disease in women.
        J Epidemiol. 2003; 13: 1-14
        • Benjamin E.J.
        • et al.
        Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association.
        Circulation. 2017; 135: e146-e603
        • Gerhard M.
        • Baum P.
        • Raby K.E.
        Peripheral arterial-vascular disease in women: prevalence, prognosis, and treatment.
        Cardiology. 1995; 86: 349-355
        • Vouyouka A.G.
        • et al.
        Lessons learned from the analysis of gender effect on risk factors and procedural outcomes of lower extremity arterial disease.
        J Vasc Surg. 2010; 52: 1196-1202
        • Choi K.H.
        • et al.
        Sex Differences in Outcomes Following Endovascular Treatment for Symptomatic Peripheral Artery Disease: An Analysis From the K- VIS ELLA Registry.
        J Am Heart Assoc. 2019; 8: e010849
        • Hassan A.
        • et al.
        Impact of Gender Differences on Outcomes of Peripheral Artery Disease Intervention (from a Nationwide Sample).
        Am J Cardiol. 2021; 141: 127-132
        • LeFevre M.L.
        Screening for abdominal aortic aneurysm: U.S. Preventive Services Task Force recommendation statement.
        Ann Intern Med. 2014; 161: 281-290
        • Care C.T.F.o.P.H.
        Recommendations on screening for abdominal aortic aneurysm in primary care.
        Canadian Medical Association Journal. 2017; 189: E1137-E1145
      10. Mofidi, R., et al., Influence of sex on expansion rate of abdominal aortic aneurysms. Br J Surg, 2007. 94(3): p. 310-314.

        • Lo R.C.
        • et al.
        Relative importance of aneurysm diameter and body size for predicting abdominal aortic aneurysm rupture in men and women.
        J Vasc Surg. 2014; 59: 1209-1216
        • Chaikof E.L.
        • et al.
        The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm.
        J Vasc Surg. 2018; 67: 2-77.e2
        • Jelani Q.U.
        • et al.
        Peripheral Arterial Disease in Women: an Overview of Risk Factor Profile, Clinical Features, and Outcomes.
        Curr Atheroscler Rep. 2018; 20: 40
        • Mayor J.M.
        • et al.
        Persistent under-representation of female patients in United States trials of common vascular diseases from 2008 to 2020.
        J Vasc Surg. 2022; 75: 30-36
        • Vyas M.V.
        • et al.
        Stroke Incidence by Sex Across the Lifespan.
        Stroke. 2021; 52: 447-451
      11. Field T, K.N., Lindsay P. DIFFERENCES IN STROKE CARE AND OUTCOMES BETWEEN WOMEN AND MEN IN CANADA. In: INTERNATIONAL JOURNAL OF STROKE. Vol 13. SAGE PUBLICATIONS LTD 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND; 2018:94-95.

      12. Kamal N, F.T., Lindsay P. ACUTE STROKE TRANSFER FOR ENDOVASCULAR THERAPY: DIFFERENCES BETWEEN WOMEN AND MEN IN CANADA. In: INTERNATIONAL JOURNAL OF STROKE. Vol 13. SAGE PUBLICATIONS LTD 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND; 2018:16-16.

      13. Bushnell, C., et al., Sex differences in the evaluation and treatment of acute ischaemic stroke. Lancet Neurol, 2018. 17(7): p. 641-650.

        • Carcel C.
        • et al.
        Sex differences in treatment and outcome after stroke: Pooled analysis including 19,000 participants.
        Neurology. 2019; 93: e2170-e2180
        • Beal C.C.
        Women's interpretation of and cognitive and behavioral responses to the symptoms of acute ischemic stroke.
        J Neurosci Nurs. 2014; 46: 256-266
        • Reeves M.J.
        • et al.
        Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes.
        Lancet Neurol. 2008; 7: 915-926
      14. Tang, J.G., N; Truong, J. Insights on Canadian Society: Living alone in Canada. 2019 [cited 2022; Available from: https://www150.statcan.gc.ca/n1/pub/75-006-x/2019001/article/00003-eng.htm.

        • Yellen S.B.
        • Cella D.F.
        Someone to live for: social well-being, parenthood status, and decision-making in oncology.
        J Clin Oncol. 1995; 13: 1255-1264
        • Visser A.
        • et al.
        Accepting or declining dialysis: considerations taken into account by elderly patients with end-stage renal disease.
        J Nephrol. 2009; 22: 794-799
        • Teixeira A.A.
        • et al.
        What do Canadians think of advanced care planning? Findings from an online opinion poll.
        BMJ Support Palliat Care. 2015; 5: 40-47
        • Merino J.G.
        • et al.
        Predictors of acute stroke mimics in 8187 patients referred to a stroke service.
        J Stroke Cerebrovasc Dis. 2013; 22: e397-403
        • Newman-Toker D.E.
        • et al.
        Missed diagnosis of stroke in the emergency department: a cross-sectional analysis of a large population-based sample.
        Diagnosis (Berl). 2014; 1: 155-166
        • Liberman A.L.
        • et al.
        Assessing diagnostic error in cerebral venous thrombosis via detailed chart review.
        Diagnosis (Berl). 2019; 6: 361-367
        • Emberson J.
        • et al.
        Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.
        The Lancet. 2014; 384: 1929-1935
        • Saver J.L.
        • et al.
        Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis.
        JAMA. 2016; 316: 1279-1289
        • Rothwell P.M.
        Antiplatelet Treatment to Prevent Early Recurrent Stroke.
        New England Journal of Medicine. 2020; 383: 276-278
        • Yafasova A.
        • et al.
        Time to Thrombolysis and Long-Term Outcomes in Patients With Acute Ischemic Stroke: A Nationwide Study.
        Stroke. 2021; 52: 1724-1732
        • Bakradze E.
        • Liberman A.L.
        Diagnostic Error in Stroke-Reasons and Proposed Solutions.
        Curr Atheroscler Rep. 2018; 20: 11
        • Yu A.Y.X.
        • et al.
        Sex Differences in Presentation and Outcome After an Acute Transient or Minor Neurologic Event.
        JAMA Neurol. 2019; 76: 962-968
        • Joundi R.A.
        • et al.
        Age-Specific and Sex-Specific Trends in Life-Sustaining Care After Acute Stroke.
        J Am Heart Assoc. 2021; 10: e021499
        • Yu A.Y.X.
        • et al.
        Sex differences in direct healthcare costs following stroke: a population-based cohort study.
        BMC Health Services Research. 2021; 21: 619
        • Yu A.Y.X.
        • et al.
        Sex Differences in Care Need and Survival in Patients Admitted to Nursing Home Poststroke.
        Can J Neurol Sci. 2020; 47: 153-159
        • Phan H.T.
        • et al.
        Factors contributing to sex differences in functional outcomes and participation after stroke.
        Neurology. 2018; 90: e1945-e1953
      15. University of Ottawa Heart Institute. Canadian Women’s Heart Health Centre. n.d.; Available from: https://cwhhc.ottawaheart.ca/.

        • Pilote L.
        • Raparelli V.
        Participation of Women in Clinical Trials.
        Journal of the American College of Cardiology. 2018; 71: 1970-1972
        • Burgess S.
        • et al.
        Women and Cardiology: The Value of Diversity.
        Heart Lung Circ. 2021; 30: 3-5
        • Han J.K.
        • et al.
        A Look Back, A Path Forward: Moving Toward Diversity and Inclusion in Cardiovascular Society Presidents.
        JACC Case Rep. 2022; 4: 247-253