How do sex differences affect atrial fibrillation?

Atrial fibrillation (AFib) is the most common sustained heart arrhythmia.¹ It affects over 46 million individuals worldwide, and up to 6 million in the United States (U.S.)² Significant differences in AFib incidence, symptomatology, complications, and treatment outcomes exist between men and women.^1,3,4 Clinicians must be aware of these differences to offer optimal patient-centered gender-specific care.

Gender Differences in AFib Prevalence

The huge 2018 ARIC study (Atherosclerosis Risk in Communities) followed over 15,000 participants in the U.S. longitudinally for a mean follow-up of 21 years to identify the lifetime risk of developing AFib.⁵ The study found that the lifetime risk of AFib was 36% (95% confidence interval, 32%–38%) among white men, 30% (95% confidence interval, 26%–32%) in white women, 21% (95% confidence interval, 13%–24%) in African American men, and 22% (95% confidence interval, 16%–25%) in African American women.

However, the 2022 VITAL Rhythm study found that when differences in height are accounted for, women are 50% more likely than males to develop AFib.³

Further, a recent review of the literature highlighted that in populations over 75 years of age, women show a greater prevalence of AFib than men, with about 55% of new cases being in women.¹ This age-related change in incidence appears to be largely due to gender differences in lifespan.

Prevalence rates may also reflect the fact that AFib is frequently unrecognized and underdiagnosed.⁶ AFib may be more underdiagnosed in women than it is in men because men typically present with more suggestive symptoms, such as palpitations and chest pain, whereas women frequently report more nonspecific symptoms, such as fatigue and dizziness.¹

These prevalence data suggest the importance of a high degree of clinical suspicion and a low threshold for investigation, especially among women. This underpins the value of   easy-to-use home devices, such as OMRON’s home blood pressure (BP) monitors with AFib screening technology.

Gender Differences in AFib Symptoms

Men tend to experience AFib with more classic symptoms, including rapid heartbeat and shortness of breath. In contrast, women often report more generalized symptoms such as fatigue, dizziness, and anxiety​.^1,7

Additionally, women are more likely to experience frequent and more severe symptoms than men. Women, on average, have higher resting heart rates than men, which may underpin men's tendency to experience more rapid and uncontrolled AFib, corresponding with more severe symptoms.⁸

A large (n = 2493) study found that women experienced a greater symptom burden than men and were more negatively affected in all health-related quality of life (HRQoL) measures except for negative impact on sex life.⁹

Despite their more severe symptoms, women tend to present much later after symptoms develop than do men.^1,7 This paradox suggests that women may tolerate or endure a longer period of untreated AFib before seeking medical attention or receiving a diagnosis. As well, it has been suggested that gender differences in symptom perception and interpretation may influence the types of symptoms women choose to report, to whom they report their symptoms, and even the response they receive from healthcare providers.^8,10

Gender Differences in AFib Stroke Risk

Women with AFib face a greater risk of ischemic stroke compared to men, even after adjusting for age and other factors​. Indeed, in 2010, female gender was added as a risk factor to the CHA2DS2-VASc risk scoring system.¹ This reflected data from the 2005 ATRIA study and data from the Framingham heart study that identified female gender as an independent risk factor for thromboembolic stroke in AFib.⁴

This finding has been generally upheld by a number of studies since then, although the effect appears to be diminished in women younger than 65.^4,13 Nevertheless, there has been some debate centered on the role of additional risk factors and delayed anticoagulation therapy in women. A huge (n = 239 671 patients with AFib) 2018 retrospective study by Nielsen and colleagues found that women with AFib and one or more non-gender risk factors had a 23% higher risk of stroke than men. The authors concluded that AFib is a stroke risk modifier rather than a risk factor.¹³

Equality in Treatment: Are Women Receiving Equal Care?

Our understanding of how to treat women for AFib and stroke prevention may be lagging due to the underrepresentation of women in AFib clinical trials and studies.¹ Women have biological differences that make treatment with complex medications challenging; for example, they are generally more susceptible to overdose, more sensitive to adverse drug events, and take more medications than men, imparting a higher risk of drug–drug interactions.^4,10 Similarly, women may have physiological differences underlying their AFib, such as differences in atrial remodeling.¹

Women are less likely to receive rhythm control treatment, including catheter ablation.¹ Similarly, the huge 2017 PINNACLE study found that in the U.S., women with AFib were significantly less likely to receive guideline-concordant oral anticoagulants overall and at all levels of the CHA₂DS₂‐VASc score.^11,12

Mechanisms Underpinning Sex Differences

As we have discussed, women have a higher incidence of AFib, present differently, have a different risk profile for complications, and are treated differently than men.

Several factors contribute to these sex disparities, including hormonal influences. Estrogen, for example, has been linked to increased clot formation, which may partly explain why women with AFib have a higher stroke risk than men​.³

Additionally, structural differences in the heart may play a role. Women with AFib have been shown to develop more atrial fibrosis compared to men, which can make certain treatments like catheter ablation less effective​.¹

Pregnancy is another factor that may influence AFib risk. Research indicates that women who have had multiple pregnancies are at a higher risk of developing AFib later in life, likely due to the cardiovascular stress of pregnancy​.¹

Addressing Gender Differences in AFib

To ensure equitable care, more research is needed to understand the underlying mechanisms that drive gender differences and how treatment can be optimized for women. For example, the following research areas have been suggested:¹

• Gender differences in atrial electrophysiology and atrial fibrosis and atrial remodeling;

• Reasons for increased stroke risk in women; and

• Reasons for gender differences in complication rates and outcomes after catheter ablation.

The data suggest that sex-specific approaches to both the prevention and treatment of AFib are required. Research needs to be compiled, for example, for optimal rate control strategies for women and for treatment guidelines for antiarrhythmics and oral anticoagulants.¹

In the meantime, clinicians should familiarize themselves with the differences in clinical presentation in women so that a higher level of clinical suspicion may help narrow the diagnosis gap between men and women with AFib.

Moreover, one way to better manage care, regardless of sex, is through home monitoring. This can be achieved with OMRON 7 Series and 10 Series AFib blood pressure monitors with the latest AFib detection functionality.

By Andrew Proulx, MD