Atrial fibrillation (AF) is the most common heart rhythm disorder in the world, and its incidence appears to be increasing.1 Some projections suggest that in the next 30 years, there will be almost 16 million active cases of AF in the United States alone. Currently, it is estimated that nearly 2 million women and 2.7 million men worldwide are diagnosed with atrial fibrillation on an annual basis.2 While the prevalence of AF is higher in men than in women at all ages, the overall absolute number of women worldwide living with AF is higher than that of men.3 As women age, the number who develop atrial fibrillation significantly increases above age 75, and much of this is due to the fact that women tend to have a longer lifespan than men.
In addition, AF incidence is more prevalent in developed countries throughout the world — a finding that is most likely due to better healthcare systems (patients live longer) as well as more sophisticated public health surveillance methods.
Gender Disparities in Disease Presentation and Progression
More than 43 million women are currently living with some form of cardiovascular disease. In 2007, heart disease claimed one female life per minute — which is more deaths than cancer, accidents, and Alzheimer’s disease combined. One in three women in the U.S. today will die from heart disease, and more women than men die from heart disease every single year.4 Women with ischemic heart disease are known to present differently than men, and their clinical course can also be quite atypical; atrial fibrillation is no exception — women are also affected differently by AF. Their clinical course and prognosis appear to have a higher morbidity and mortality as compared to men.5 Most significantly, women with AF appear to have a higher incidence of stroke, particularly when over age 75.6-8 In general, women tend to be more symptomatic, less tolerant of antiarrhythmic drugs, and have higher heart rates at presentation.9 Moreover, women tend to report more symptoms of palpitations and anxiety, and have more frequent (and longer) episodes of symptomatic paroxysmal AF.10 Overall, women with atrial fibrillation report a much lower quality of life, and fatigue and depression are more prevalent.11
Stroke and Atrial Fibrillation in Women
Multiple studies have shown that atrial fibrillation confers a five-fold increased risk for stroke in all patients. Moreover, stroke in AF also has a higher rate of recurrence and has an overall higher rate of morbidity and mortality as compared to stroke that results from other causes.1 Women with AF tend to be at a higher absolute risk for stroke — even when anticoagulated. In fact, the Framingham study demonstrated a higher rate of death in women with AF — most of these deaths were due to either stroke or heart failure.12 Stroke in women tends to present with more severe neurological symptoms, and in general, women with stroke are older than males — which may account for the more severe neurologic impairment seen in women 3 months from the event. More concerning is the fact that women are less likely to be anticoagulated at discharge after a stroke.
Women do seem to derive more benefit from anticoagulation in AF, and this finding is consistent between both warfarin as well as with novel oral anticoagulants (NOACs).13 Moreover, there are no differences in bleeding risk between men and women who are appropriately anticoagulated and monitored. In fact, there are some emerging data that suggest that women may in fact receive an even greater benefit from NOACs as compared to men. Surprisingly, women are less likely to be anticoagulated as compared to men.10 While it is clear that women have higher stroke risk and gain an even greater benefit from anticoagulation, data suggests that women on warfarin spend more time out of the therapeutic range and are less likely to be referred for home self-monitoring of INR.14
Gender Disparities in AF Treatment
In general, women with cardiovascular disease are not treated as aggressively as men — women with ischemic heart disease are less likely to be treated with an early interventional approach. Women discharged from the hospital after myocardial infarction are also less likely to be prescribed appropriate secondary prevention drugs and are not referred for cardiac rehabilitation at the same rate as men. Disparities in treatment are also very much apparent when it comes to the use of advanced treatments for atrial fibrillation.15 Men with AF are far more likely to be treated aggressively with ablation therapy as compared to women with similar characteristics and risk profiles. In addition, women tend to be treated with a rate control strategy more frequently than men.16 While men are more likely to be treated with a Class 1 or Class 3 antiarrhythmic drug, women are more likely to be prescribed a beta blocker or digoxin. Women tend to spend more time in AF prior to treatment, have more refractory AF, and ultimately have a more difficult to control arrhythmia in the end. When women are given antiarrhythmic therapy, they are more likely to experience bradycardia.10 Moreover, due to hormonal fluctuations that affect QT interval, women who are given Class 3 antiarrhythmic drugs have a higher incidence of torsades de pointes.17
Ablative therapy is now an accepted first-line approach in many patients with paroxysmal AF. However, women are much less likely to undergo ablation procedures early in the course of their disease. In fact, when referred for ablation, women have a higher AF burden, more symptoms, and larger atrial size.18 It is clear that women do have higher rates of bleeding and other peri-procedural complications — women have a complication rate of 5% as compared to 2.4% for men. While there is some conflicting evidence, most studies do not show gender as an independent predictor of AF ablation success or failure.
What Can We Do to Improve AF Care for Women?
It is essential that we redouble our efforts when it comes to the treatment of women with atrial fibrillation. Women with cardiovascular disease are clearly undertreated and underserved. In order to better treat women with AF, we must strive to intervene much earlier in the course of their disease process. We must encourage our colleagues to refer female AF patients to an electrophysiologist much sooner. Healthcare providers must better understand the way in which women with AF present, how their disease progresses, and how gender may affect response to therapy. Most importantly, we must all be cognizant of the fact that women are more likely to have an AF-related embolic stroke and that women gain an even bigger benefit from appropriate anticoagulation.
We must also consider ablation earlier for women with AF and understand that peri-procedural complications occur at a higher rate. We must take extra care to avoid bleeding and vascular complications in women and employ very close intra- and post-procedural monitoring to ensure that both male and female patients have excellent ablation outcomes.
Ultimately, we must all serve as advocates for women’s cardiac health. As leaders in the treatment of heart rhythm disorders, we must all work to raise awareness of women and cardiovascular disease through advocacy, education, and research.
Kevin R. Campbell, MD, FACC is with North Carolina Heart and Vascular and UNC Healthcare. He is also Assistant Professor at UNC Department of Medicine, Division of Cardiology, and Director of Electrophysiology at Johnston Health. In addition, Dr. Campbell is President of K-Roc Consulting, LLC.
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- European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369-2429.
- Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129(8):837-847.
- 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(5):469-473.
- Adapted from American Heart Association, the Nurse’s Health Study. WISE and Acute Coronary Syndromes Without Chest Pain: Insights from GRACE.
- Wagstaff AJ, Overard TF, Lip GY, Lane DA. Is female sex a risk factor for stroke and thromboembolism in patients with atrial fibrillation? A systematic review and meta-analysis. QJM. 2014;107(12):955-967.
- Madias C, Trohman RG. The link between atrial fibrillation and stroke in women. Womens Health (Lond Engl). 2011;7(3):375-382.
- Fang MC, Singer DE, Chang Y, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation. 2005;112(12):1687-1691.
- Andersson T, Magnuson A, Bryngelsson IL, et al. Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: a nationwide cohort study of 9519 patients. Int J Cardiol. 2014;177(1):91-99.
- Rienstra M, van Veldhuisen DJ, Hagens VE, et al. Gender-related differences in rhythm control treatment in persistent atrial fibrillation: data of the Rate Control Versus Electrical Cardioversion (RACE) study. J Am Coll Cardiol. 2005;46:1298-1130.
- Humphries KH, Kerr CR, Connolly SJ, et al. New-onset atrial fibrillation: sex differences in presentation, treatment, and outcome. Circulation. 2001;103(19):2365-2370.
- Paquette M, Roy D, Talajic M, et al. Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation. Am J Cardiol. 2000;86(7):764-768.
- Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-952.
- Michelena HI, Powell BD, Brady PA, Friedman PA, Ezekowitz MD. Gender in atrial fibrillation: ten years later. Gend Med. 2010;7:206-217.
- Sullivan RM, Zhang J, Zamba G, Lip GY, 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(12):1799-1802.
- Santageli PS, Di Biase L, Pelargonio G, Natale A. Outcome of invasive electrophysiological procedures and gender: are males and females the same? J Cardiovasc Electrophysiol. 2011;22:605-612.
- Friberg L, Benson L, Rosenqvist M, Lip GY. Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study. BMJ. 2012;344:e3522
- Nakagawa M, Ooie T, Takahashi N, et al. Influence of menstrual cycle on QT interval dynamics. Pacing Clin Electrophysiol. 2006;29:607-613.
- Patel D, Mohanty P, Di Biase L, et al. Outcome and complications of catheter ablation for atrial fibrillation in females. Heart Rhythm. 2010;7:167-172.