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Canadian Journal of Cardiology

Sex Differences in Atrial Fibrillation

  • Jason G. Andrade
    Correspondence
    Corresponding author: Dr Jason G. Andrade, Division of Cardiology, University of British Columbia, 2775 Laurel St, Vancouver, British Columbia V5Z 1M9, Canada. Tel.: +1-604-875-5069; fax: +1-604-875-5874.
    Affiliations
    Montreal Heart Institute, Department of Medicine, Université de Montréal, Montreal, Quebec, Canada

    Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Marc W. Deyell
    Affiliations
    Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Andrea Y.K. Lee
    Affiliations
    Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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  • Laurent Macle
    Affiliations
    Montreal Heart Institute, Department of Medicine, Université de Montréal, Montreal, Quebec, Canada
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Published:December 05, 2017DOI:https://doi.org/10.1016/j.cjca.2017.11.022

      Abstract

      Atrial fibrillation (AF) is a chronic progressive disease characterized by exacerbations and remissions. It remains the most common sustained arrhythmia seen in clinical practice, and represents a major burden to health care systems. Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology (lower rate of prevalence in women, women present at a later age), pathophysiology (sex-related differences in AF triggers and substrate), clinical presentation (women are more likely symptomatic, with relatively more severe symptoms), and natural history. Moreover, similar to other cardiovascular conditions there are substantial sex-specific differences in the management of AF, with women being significantly less likely to receive therapeutic anticoagulation, attempts at rhythm control, or undergo invasive cardiovascular procedures. The purpose of this review is to explore these sex-specific differences.

      Résumé

      La fibrillation auriculaire (FA) est une maladie chronique évolutive qui est caractérisée par des périodes d’exacerbation et de rémission. Elle demeure l’arythmie soutenue la plus fréquemment observée dans la pratique clinique et constitue un fardeau considérable pour les systèmes de soins de santé. Au même titre que les autres maladies cardiovasculaires, on a observé des différences importantes entre les sexes en ce qui concerne l’épidémiologie (taux de prévalence plus faibles chez les femmes, et à un âge plus avancé), la physiopathologie (différences entre les sexes pour ce qui est des facteurs déclenchants et du substrat de la FA), le tableau clinique (les femmes sont plus susceptibles de présenter des symptômes, voire des symptômes plus graves) et l’évolution naturelle de la maladie. En outre, comme dans les autres maladies cardiovasculaires, les femmes montrent des différences substantielles dans la prise en charge de la FA, puisqu’elles sont beaucoup moins susceptibles de recevoir une anticoagulation thérapeutique, de tenter un traitement régulateur du rythme ou de subir des interventions invasives de chirurgie cardiovasculaire. L’objectif de cette revue est d’examiner ces différences entre les sexes.
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      References

        • Andrade J.
        • Khairy P.
        • Dobrev D.
        • Nattel S.
        The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.
        Circ Res. 2014; 114: 1453-1468
        • Miyasaka Y.
        • Barnes M.E.
        • Gersh B.J.
        • et al.
        Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence.
        Circulation. 2006; 114: 119-125
        • Schnabel R.B.
        • Yin X.
        • Gona P.
        • et al.
        50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study.
        Lancet. 2015; 386: 154-162
        • Wilke T.
        • Groth A.
        • Mueller S.
        • et al.
        Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients.
        Europace. 2013; 15: 486-493
        • Piccini J.P.
        • Hammill B.G.
        • Sinner M.F.
        • et al.
        Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries, 1993-2007.
        Circ Cardiovasc Qual Outcomes. 2012; 5: 85-93
        • Svennberg E.
        • Engdahl J.
        • Al-Khalili F.
        • et al.
        Mass screening for untreated atrial fibrillation: the STROKESTOP study.
        Circulation. 2015; 131: 2176-2184
        • Lloyd-Jones D.M.
        • Wang T.J.
        • Leip E.P.
        • et al.
        Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.
        Circulation. 2004; 110: 1042-1046
        • Heeringa J.
        • van der Kuip D.A.
        • Hofman A.
        • et al.
        Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study.
        Eur Heart J. 2006; 27: 949-953
        • Benjamin E.J.
        • Levy D.
        • Vaziri S.M.
        • et al.
        Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study.
        JAMA. 1994; 271: 840-844
        • Kerr C.R.
        • Humphries K.
        Gender-related differences in atrial fibrillation.
        J Am Coll Cardiol. 2005; 46: 1307-1308
        • Frost L.
        • Hune L.J.
        • Vestergaard P.
        Overweight and obesity as risk factors for atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study.
        Am J Med. 2005; 118: 489-495
        • Oyen N.
        • Ranthe M.F.
        • Carstensen L.
        • et al.
        Familial aggregation of lone atrial fibrillation in young persons.
        J Am Coll Cardiol. 2012; 60: 917-921
        • Zoller B.
        • Ohlsson H.
        • Sundquist J.
        • Sundquist K.
        High familial risk of atrial fibrillation/atrial flutter in multiplex families: a nationwide family study in Sweden.
        J Am Heart Assoc. 2012; 2: e003384
        • Liu X.K.
        • Jahangir A.
        • Terzic A.
        • et al.
        Age- and sex-related atrial electrophysiologic and structural changes.
        Am J Cardiol. 2004; 94: 373-375
        • Nattel S.
        Atrial fibrillation and body composition: is it fat or lean that ultimately determines the risk?.
        J Am Coll Cardiol. 2017; 69: 2498-2501
        • Cochet H.
        • Mouries A.
        • Nivet 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
        • Tsai W.C.
        • Chen Y.C.
        • Lin Y.K.
        • Chen S.A.
        • Chen Y.J.
        Sex differences in the electrophysiological characteristics of pulmonary veins and left atrium and their clinical implication in atrial fibrillation.
        Circ Arrhythm Electrophysiol. 2011; 4: 550-559
        • Takigawa M.
        • Kuwahara T.
        • Takahashi A.
        • et al.
        Differences in catheter ablation of paroxysmal atrial fibrillation between males and females.
        Int J Cardiol. 2013; 168: 1984-1991
        • Ravn L.S.
        • Hofman-Bang J.
        • Dixen U.
        • et al.
        Relation of 97T polymorphism in KCNE5 to risk of atrial fibrillation.
        Am J Cardiol. 2005; 96: 405-407
        • Tsuneda T.
        • Yamashita T.
        • Kato T.
        • et al.
        Deficiency of testosterone associates with the substrate of atrial fibrillation in the rat model.
        J Cardiovasc Electrophysiol. 2009; 20: 1055-1060
        • Magnani J.W.
        • Moser C.B.
        • Murabito J.M.
        • et al.
        Association of sex hormones, aging, and atrial fibrillation in men: the Framingham Heart Study.
        Circ Arrhythm Electrophysiol. 2014; 7: 307-312
        • Nakamura H.
        • Kurokawa J.
        • Bai C.X.
        • et al.
        Progesterone regulates cardiac repolarization through a nongenomic pathway: an in vitro patch-clamp and computational modeling study.
        Circulation. 2007; 116: 2913-2922
        • Rosano G.M.
        • Leonardo F.
        • Dicandia C.
        • et al.
        Acute electrophysiologic effect of estradiol 17beta in menopausal women.
        Am J Cardiol. 2000; 86 (1385-1387, A5-A6)
        • Saba S.
        • Zhu W.
        • Aronovitz M.J.
        • et al.
        Effects of estrogen on cardiac electrophysiology in female mice.
        J Cardiovasc Electrophysiol. 2002; 13: 276-280
        • Jovanovic S.
        • Jovanovic A.
        • Shen W.K.
        • Terzic A.
        Low concentrations of 17beta-estradiol protect single cardiac cells against metabolic stress-induced Ca2+ loading.
        J Am Coll Cardiol. 2000; 36: 948-952
        • Stumpf W.E.
        • Sar M.
        • Aumuller G.
        The heart: a target organ for estradiol.
        Science. 1977; 196: 319-321
        • Rosano G.M.
        • Leonardo F.
        • Sarrel P.M.
        • et al.
        Cyclical variation in paroxysmal supraventricular tachycardia in women.
        Lancet. 1996; 347: 786-788
        • Perez M.V.
        • Wang P.J.
        • Larson J.C.
        • et al.
        Effects of postmenopausal hormone therapy on incident atrial fibrillation: the Women’s Health Initiative randomized controlled trials.
        Circ Arrhythm Electrophysiol. 2012; 5: 1108-1116
        • Xiong Q.
        • Proietti M.
        • Senoo K.
        • Lip G.Y.
        Asymptomatic versus symptomatic atrial fibrillation: a systematic review of age/gender differences and cardiovascular outcomes.
        Int J Cardiol. 2015; 191: 172-177
        • Ball J.
        • Carrington M.J.
        • Wood K.A.
        • Stewart S.
        • SAFETY Investigators
        Women versus men with chronic atrial fibrillation: insights from the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY).
        PLoS One. 2013; 8: e65795
        • Scheuermeyer F.X.
        • Mackay M.
        • Christenson J.
        • et al.
        There are sex differences in the demographics and risk profiles of emergency department (ED) patients with atrial fibrillation and flutter, but no apparent differences in ED management or outcomes.
        Acad Emerg Med. 2015; 22: 1067-1075
        • Blum S.
        • Muff C.
        • Aeschbacher S.
        • et al.
        Prospective assessment of sex-related differences in symptom status and health perception among patients with atrial fibrillation.
        J Am Heart Assoc. 2017; 6: e005401
        • Reynolds M.R.
        • Lavelle T.
        • Essebag V.
        • Cohen D.J.
        • Zimetbaum P.
        Influence of age, sex, and atrial fibrillation recurrence on quality of life outcomes in a population of patients with new-onset atrial fibrillation: the Fibrillation Registry Assessing Costs, Therapies, Adverse events and Lifestyle (FRACTAL) study.
        Am Heart J. 2006; 152: 1097-1103
        • Hnatkova K.
        • Waktare J.E.
        • Murgatroyd F.D.
        • et al.
        Age and gender influences on rate and duration of paroxysmal atrial fibrillation.
        Pacing Clin Electrophysiol. 1998; 21: 2455-2458
        • Piccini J.P.
        • Sinner M.F.
        • Greiner M.A.
        • et al.
        Outcomes of Medicare beneficiaries undergoing catheter ablation for atrial fibrillation.
        Circulation. 2012; 126: 2200-2207
        • Emdin C.A.
        • Wong C.X.
        • Hsiao A.J.
        • et al.
        Atrial fibrillation as risk factor for cardiovascular disease and death in women compared with men: systematic review and meta-analysis of cohort studies.
        BMJ. 2016; 532: h7013
        • Wang T.J.
        • Massaro J.M.
        • Levy D.
        • et al.
        A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study.
        JAMA. 2003; 290: 1049-1056
        • Friberg J.
        • Scharling H.
        • Gadsboll N.
        • et al.
        Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study).
        Am J Cardiol. 2004; 94: 889-894
        • Friberg L.
        • Rosenqvist M.
        • Lip G.Y.
        Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study.
        Eur Heart J. 2012; 33: 1500-1510
        • Olesen J.B.
        • Torp-Pedersen C.
        • Hansen M.L.
        • Lip G.Y.
        The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study.
        Thromb Haemost. 2012; 107: 1172-1179
        • Mikkelsen A.P.
        • Lindhardsen J.
        • Lip G.Y.
        • et al.
        Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study.
        J Thromb Haemost. 2012; 10: 1745-1751
        • Macle L.
        • Cairns J.
        • Leblanc K.
        • et al.
        2016 focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation.
        Can J Cardiol. 2016; 32: 1170-1185
        • Kirchhof P.
        • Benussi S.
        • Kotecha D.
        • et al.
        2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
        Europace. 2016; 18: 1609-1678
        • Andrade J.G.
        • Macle L.
        • Nattel S.
        • Verma A.
        • Cairns J.
        Contemporary atrial fibrillation management: a comparison of the current AHA/ACC/HRS, CCS, and ESC guidelines.
        Can J Cardiol. 2017; 33: 965-976
        • Appelros P.
        • Stegmayr B.
        • Terent A.
        A review on sex differences in stroke treatment and outcome.
        Acta Neurol Scand. 2010; 121: 359-369
        • Miyasaka Y.
        • Barnes M.E.
        • Petersen R.C.
        • et al.
        Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a community-based cohort.
        Eur Heart J. 2007; 28: 1962-1967
        • Schnabel R.B.
        • Rienstra M.
        • Sullivan L.M.
        • et al.
        Risk assessment for incident heart failure in individuals with atrial fibrillation.
        Eur J Heart Fail. 2013; 15: 843-849
        • Meyer S.
        • Brouwers F.P.
        • Voors A.A.
        • et al.
        Sex differences in new-onset heart failure.
        Clin Res Cardiol. 2015; 104: 342-350
        • Hsu J.C.
        • Maddox T.M.
        • Kennedy K.
        • et al.
        Aspirin instead of oral anticoagulant prescription in atrial fibrillation patients at risk for stroke.
        J Am Coll Cardiol. 2016; 67: 2913-2923
        • Avgil Tsadok M.
        • Jackevicius C.A.
        • Rahme E.
        • Humphries K.H.
        • Pilote L.
        Sex differences in dabigatran use, safety, and effectiveness in a population-based cohort of patients with atrial fibrillation.
        Circ Cardiovasc Qual Outcomes. 2015; 8: 593-599
        • Olesen J.B.
        • Sorensen R.
        • Hansen M.L.
        • et al.
        Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naive atrial fibrillation patients: Danish nationwide descriptive data 2011-2013.
        Europace. 2015; 17: 187-193
        • Garcia D.
        • Regan S.
        • Crowther M.
        • Hughes R.A.
        • Hylek E.M.
        Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population.
        Chest. 2005; 127: 2049-2056
        • Pancholy S.B.
        • Sharma P.S.
        • Pancholy D.S.
        • 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
        • Granger C.B.
        • Alexander J.H.
        • McMurray J.J.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2011; 365: 981-992
        • Giugliano R.P.
        • Ruff C.T.
        • Braunwald E.
        • et al.
        Edoxaban versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2013; 369: 2093-2104
        • Patel M.R.
        • Mahaffey K.W.
        • Garg J.
        • et al.
        Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
        N Engl J Med. 2011; 365: 883-891
        • Connolly S.J.
        • Ezekowitz M.D.
        • Yusuf S.
        • et al.
        Dabigatran versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2009; 361: 1139-1151
        • Ruff C.T.
        • Giugliano R.P.
        • Braunwald E.
        • et al.
        Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.
        Lancet. 2014; 383: 955-962
        • Dagres N.
        • Nieuwlaat R.
        • Vardas P.E.
        • et al.
        Gender-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Heart Survey on Atrial Fibrillation.
        J Am Coll Cardiol. 2007; 49: 572-577
        • Lip G.Y.
        • Laroche C.
        • Boriani G.
        • et al.
        Sex-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe: a report from the Euro Observational Research Programme Pilot survey on Atrial Fibrillation.
        Europace. 2015; 17: 24-31
        • Van Gelder I.C.
        • Hagens V.E.
        • Bosker H.A.
        • et al.
        A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.
        N Engl J Med. 2002; 347: 1834-1840
        • Wyse D.G.
        • Waldo A.L.
        • DiMarco J.P.
        • et al.
        A comparison of rate control and rhythm control in patients with atrial fibrillation.
        N Engl J Med. 2002; 347: 1825-1833
        • Mitoff P.R.
        • Gam D.
        • Ivanov J.
        • et al.
        Cardiac-specific sympathetic activation in men and women with and without heart failure.
        Heart. 2011; 97: 382-387
        • Luzier A.B.
        • Killian A.
        • Wilton J.H.
        • et al.
        Gender-related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers.
        Clin Pharmacol Ther. 1999; 66: 594-601
        • Pratt C.M.
        • Camm A.J.
        • Cooper W.
        • et al.
        Mortality in the Survival With ORal D-sotalol (SWORD) trial: why did patients die?.
        Am J Cardiol. 1998; 81: 869-876
        • Torp-Pedersen C.
        • Moller M.
        • Bloch-Thomsen P.E.
        • et al.
        Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.
        N Engl J Med. 1999; 341: 857-865
        • Ganesan A.N.
        • Shipp N.J.
        • Brooks A.G.
        • et al.
        Long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis.
        J Am Heart Assoc. 2013; 2: e004549
        • Schnabel R.B.
        • Pecen L.
        • Ojeda F.M.
        • et al.
        Gender differences in clinical presentation and 1-year outcomes in atrial fibrillation.
        Heart. 2017; 103: 1024-1030
        • Patel N.
        • Deshmukh A.
        • Thakkar B.
        • et al.
        Gender, race, and health insurance status in patients undergoing catheter ablation for atrial fibrillation.
        Am J Cardiol. 2016; 117: 1117-1126
        • Forleo G.B.
        • Tondo C.
        • De Luca L.
        • et al.
        Gender-related differences in catheter ablation of atrial fibrillation.
        Europace. 2007; 9: 613-620
        • Patel D.
        • Mohanty P.
        • Di Biase L.
        • et al.
        Outcomes and complications of catheter ablation for atrial fibrillation in females.
        Heart Rhythm. 2010; 7: 167-172