Gender Matters: Why Afib Is More Fatal for Women
In recent years, there have been many revelations about heart disease and how it specifically affects women. Research has shown that women frequently have different symptoms of a heart attack than men, and women are often worse off after a heart attack.1
Not surprisingly, the diagnosis, symptoms, and treatments of atrial fibrillation (afib) can differ for women, too. One stark, potentially deadly difference: in women 20 to 79 years old, the risk of stroke is 4.6-fold greater in women than men.2 In addition, mortality for women with afib is up to 2.5 times greater than that for men.3
Afib affected approximately 2.66 million people in the United States in 2010, according to the U.S. Centers for Disease Control. And the numbers will only climb. With the aging Baby Boomer population, estimates from the Centers for Disease Control indicate that afib will affect 12 million people by 2050.4 Afib sufferers have a five-fold increase in stroke risk compared to the general population. The numbers for women tell a dire story:
- Each year, in the United States, about 55,000 more women than men have strokes.5
- Stroke is the fourth leading cause of death for women.5
- Women account for more than 60 percent of stroke-related deaths.5
- After age 75, which is the median age for afib onset, 60 percent of those with afib are women.5
- Afib risk in women increases over men when patients have other conditions, such as diabetes mellitus, congestive heart failure, hypertension, valvular disease, and myocardial ischemia.6
- There have been greater declines in stroke death rates among men than in women.6
We celebrate the differences between men and women, but as far as afib and stroke are concerned, the differences can be deadly. Women are also more likely to experience longer symptomatic episodes, more frequent recurrences, and significantly higher ventricular rates during afib.7 Interestingly, women with type B blood have a 17 percent increase in stroke risk compared to men.8
Like the revelations about women and heart disease, these differences may surprise many healthcare providers. The differences also extend to how women afib patients are viewed by some healthcare providers. Too many times, women with afib symptoms are dismissed as having panic attacks or being stressed and not taken seriously. However, afib in women can be much more serious. When healthcare providers know about the differences in risk, diagnosis, and treatment, they can provide the best possible treatment to female afib sufferers.
Assessing Stroke and Bleeding Risk
To assess the stroke risk of those with afib and the need for anticoagulants, many healthcare providers use the CHADS2 and CHA2DS2-VASc scoring tools (Figure 2) to help gauge the risk of stroke and determine whether to prescribe anticoagulants. However, the CHADS2 tool fails to consider women’s apparent greater stroke risk.
For those who have a CHADS2 score of 0 or 1, meaning that anticoagulants may not be deemed necessary, considering their CHA2DS2-VASc score may provide a more accurate assessment of their true stroke risk. It incorporates vascular disease, another age range (65 to 74 years), an additional weighting for being 75 years or older, and the female gender.9 Therefore, using only the CHADS2 tool for women (and some men) who are a CHADS2 score of 0 or 1 could be a disservice to them.
When deciding whether to use anticoagulants, some healthcare providers also weigh bleeding risk. One commonly used tool that helps gauge this risk is the HAS-BLED scoring tool that takes into account major bleeding risk factors, such as Hypertension, Abnormal kidney or liver function, Stroke, Bleeding, Labile INR (unstable or high INRs, or poor time in the therapeutic range), Elderly, and Drugs or alcohol. For more information about the HAS-BLED scoring tool, see Figure 3.10 Using these tools can help optimize afib patient care.
Potential Misperceptions About Women and Afib
Healthcare providers have to be careful about afib-related misperceptions and clarify them for patients. Some media reported that a recent Danish study concluded that females with atrial fibrillation weren’t at greater risk of a stroke. These news outlets didn’t read the full study, because the authors clearly stated that for there to be no additional stroke risk, women must be younger than 65 and have no other stroke risk factors aside from afib. In other words, they must truly have lone afib.
The study authors noted that the European Society of Cardiology (ESC) guidelines (Figure 4) advise that female patients with afib take oral anticoagulants, except those who meet the “age <65 and lone AF criterion.” Female patients under 65 with just one minor risk factor, and those between 65 and 74 years of age with no additional risk factors, should be on oral anticoagulants. While these Danish study results contradict the recommendations in the guidelines because they did not find females aged less than 75 to have excess risk when compared to males, the study authors still recommended sticking to the ESC guidelines because so many other studies have reported otherwise.11
This bears emphasis: the study authors recommended that anticoagulation is not needed only for women 65 and younger with lone afib. If women have other stroke risk factors, such as diabetes, high blood pressure, or heart disease, making them a CHA2DS2-VASc score of 2 or more, they clearly need anticoagulants. To say otherwise irresponsibly jeopardizes women’s lives.
Afib affects immediate risks and the long-term prognosis of women differently than men. An analysis from the Euro Heart Survey for Afib found that women with afib have more than double the thromboembolism risk of men with afib.12 In addition, a Swedish study found that the rate of ischemic stroke in afib patients younger than 65 years of age was 47 percent higher in women than men.13 What’s worse: women overall have a significantly higher risk of afib-related stroke than men and are more likely to live with stroke-related disability. As you might imagine, women who have these stroke-related disabilities have a significantly lower quality of life.6
Sources of Afib-Related Gender Differences
While not all of the sources of afib differences between men and women are known, researchers have found some very specific afib-related differences. For example, blood pressure (BP) is strongly associated with afib in women, and systolic BP is a better predictor in women than diastolic BP.14
These differences between men and women with afib may be based in physiology, vascular biology, genetics, hormones, or thromboembolic factors. Certainly, menstrual cycles and hormones play a role in women.6 Biomarkers for inflammation, such as high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and fibrinogen, have been associated with afib in women with a history of heart disease.15 Women also live longer than men, placing them in the susceptible age range for afib for a longer amount of time.16
Social and psychological differences between men and women also relate to afib. For example, we know that cardiovascular events are more common among women who have high-stress jobs.17 Although heavy alcohol consumption is associated with higher risk of afib among men, there is no such association in women.18
Another critical difference is communication. Women communicate differently than men, and understanding those differences can go a long way to helping your afib patients. For ideas of ways to better talk with afib patients, especially women, see the sidebar “Improving Communication with Afib Patients.”
Rate and Rhythm Treatment Differences for Women with Afib
To control arrhythmia, medications are typically prescribed. Other treatments include catheter ablation and surgical ablation procedures. But there are differences in treatment, too.
Research shows that women are prescribed beta blockers and digoxin (rate control drugs) more often, whereas men are more often prescribed class I or class III anti-arrhythmic drugs (rhythm control drugs).13
What are the implications of these treatment differences? Women may be left in afib longer without treatment because the condition may not be viewed as worthy of treatment in women. Or women may just be left on rate control, which doesn’t treat the condition or the symptoms, some of which may be inaccurately attributed to aging instead of afib. For many, rate control leads to a lower quality of life as these medications may leave them fatigued and even “in a fog.”
What’s absolutely tragic: being left on rate control long term, and in afib, may allow fibrosis to continue to build in their hearts, increasing their stroke risk. While we don’t know what causes women’s greater stroke risk, perhaps delayed treatment or less aggressive treatment in women plays a role.
Anticoagulation and Bleeding Differences
There are differences related to anticoagulants, too. Women, especially those 75 years or older, have a higher risk of stroke than men, regardless of their use of warfarin.19 Women’s adherence to anticoagulants isn’t an issue, either. While some research shows that women are less adherent to medications for some chronic conditions, that doesn’t appear to be the case for warfarin adherence. When it comes to warfarin, men have been found to have lower warfarin adherence rates than women.20 Women are also at a higher risk than men for afib-related thromboembolism when off of warfarin.21
Another significant difference: women on warfarin spend more time outside of the therapeutic range than men. In a recently published study, on average, women were outside of the therapeutic range 40 percent of the time compared to men’s 37 percent. Women also spent more time below the therapeutic range, putting them at more risk for ischemic stroke, at 29 percent compared to 26 percent in men.22
Patient self-monitoring of warfarin should help women stay in therapeutic range. However, one study found more men than women (56 percent vs. 44 percent) were referred for self-monitoring, leading to the question of whether women are referred for self-monitoring less often.23
One of the most frustrating aspects of this issue has been discovering that women are sometimes told to “just take aspirin because you’re a CHADS2 score of 1, with just one risk factor, so you are at low risk,” when in fact the latest guidelines (Figure 4) indicate that having a single risk factor beyond afib increases a woman’s stroke risk and that she should consider an anticoagulant.
Even more frustrating is when women 75 or over are automatically considered to be a “fall risk,” regardless of their physical condition, and thus are not considered for an anticoagulant and then often go on to have a stroke. Warfarin is superior to aspirin in reducing the risk of stroke, especially in women, as it reduces the risk by 84 percent in them compared to 60 percent in men.6 However, women over 75 years old were 54 percent less likely to receive warfarin and twice as likely to receive aspirin. Aspirin is associated with a significantly decreased stroke risk in men (44 percent), but the risk reduction in women is about half of that (23 percent).12
But what may be even better news for women is that stroke reduction results of the newer novel oral anticoagulants are even stronger than warfarin.
When looking to prescribe anticoagulant medication to women, additional risk of bleeding shouldn’t be a concern. Studies have shown bleeding risk for men and women to be about the same.20 This is another one of those perceptions that needs to change.
Other Treatment Differences
Some other differences in afib treatment for women include:
- Electrical cardioversion is used significantly less frequently in women.24
- Procedures are usually recommended only after more antiarrhythmic drugs in women than in men.6
- Despite similar outcomes, women with afib are referred for catheter ablation less often or later than men.6
- Women are over-represented in AV node ablation and under-represented in catheter ablation, according to data from a small, private practice study.25
We need more studies to determine if the greater stroke risk for women is due to physiological differences or treatment differences, or both. In the meantime, by being aware of these differences in afib between men and women, medical professionals can design a safer, more effective, and personalized approach to managing afib.
Electrophysiology professionals, cardiologists, and GPs can have a huge positive impact by recognizing these differences in diagnosing and treating atrial fibrillation in women. Wouldn’t you want that kind of care for your mom, grandmother, sister, daughter, or spouse?
- McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circulation. 2003;108:2619-2623.
- Schnohr P, Lange P, Scharling H, Jensen JS. Long-term physical activity in leisure time and mortality from coronary heart disease, stroke, respiratory diseases, and cancer. The Copenhagen City Heart Study. Eur J Cardiovasc Prev Rehabil. 2006;13(2):173-179.
- Michelena HI, Powell BD, Brady PA, Friedman PA, Ezekowitz MD. Gender in atrial fibrillation: ten years later. Gend Med. 2010;3(7):206-217.
- “Atrial Fibrillation Fact Sheet.” Centers for Disease Control and Prevention, 20 Dec. 2010. Web. 13 Feb. 2013. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillat...
- Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics — 2012 update: a report from the American Heart Association. Circulation. 2012;125:e2-e220.
- Volgman AS, Manankil MF, Mookherjee D, Trohman RG. Women with atrial fibrillation: greater risk, less attention. Gend Med. 2009;6(3):419-32.
- Roy D, Talajic M, Dorian P, et al. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med. 2000;342(13):913-920.
- Qi L, et al. ABO Blood Group and Risk of Stroke in US Men and Women. Abstract 16887. American Heart Association, 16 Nov. 2011. Web. 13 Feb. 2013. http://newsroom.heart.org/news/wednesday-news-tips-nov-16-2011-218042
- Odum LE, Cochran KA, Aistrope DS, Snella KA. The CHADS₂ versus the new CHA2DS2-VASc scoring systems for guiding antithrombotic treatment of patients with atrial fibrillation: review of the literature and recommendations for use. Pharmacotherapy. 2012;32(3):285-296.
- Lip GY, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57(2):173-180.
- Mikkelsen AP, Lindhardsen J, Lip GY, Gislason GH, Torp-Pedersen C, Olesen JB. Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study. J Thromb Haemost. 2012;10(9):1745-1751.
- Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263–72.
- 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.
- Conen D, Tedrow UB, Koplan BA, Glynn RJ, Buring JE, Albert CM. Influence of systolic and diastolic blood pressure on the risk of incident atrial fibrillation in women. Circulation. 2009;119(16):2146-2152.
- Conen D, Ridker PM, Everett BM, et al. A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women. Eur Heart J. 2010;31:1730-1736.
- Mason PK, Moorman L, Lake D, et al. Gender and racial characteristics of patients referred to a tertiary atrial fibrillation center. JAFIB. 2010;2(3):827.
- Slopen N, Glynn RJ, Buring JE, Lewis TT, Williams DR, Albert MA. Job strain, job insecurity, and incident cardiovascular disease in the women’s health study: results from a 10-year prospective study. PLoS One. 2012;7(7):e40512.
- Mukamal KJ, Tolstrup JS, Friberg J, Jensen G, Grønbaek M. Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study. Circulation. 2005;112(12):1736-1742.
- Avgil Tsadok M, Jackevicius CA, Rahme E, Humphries KH, Behlouli H, Pilote L. Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation. JAMA. 2012;307(18):1952-1195.
- Kneeland PP, Fang MC. Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism. Patient Prefer Adherence. 2010;4:51-60.
- 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;112:1687-1691.
- 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.
- Alere STABLE Study Showed Improved Warfarin Safety. PTINR. Accessed February 2013. http://www.ptinr.com/weeklytestingworks
- Dagres N, Nieuwlaat R, Vardas PE, 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.
- Mandrola J, et al. Gender-Specific Results of Atrial Fibrillation Ablation in a Private Practice Setting. Accessed January 2013. www.drjohnm.dreamhosters.com/wp-content/uploads/2011/11/Screen-shot-2011...
- Alberts MJ, Amantangelo M, Bauer KA, et al. 2012. Assessing Stroke and Bleeding Risk in Atrial Fibrillation: Consensus statement on appropriate anticoagulant use. Washington, D.C.: Alliance for Aging Research. http://bit.ly/afib-consensus
- Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719-2747. doi:10.1093/eurheartj/ehs25