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Cited by 353Atrial Fibrillation Management and OutcomesCardiac electrophysiology and arrhythmiasAcute Ischemic Stroke Management

Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis

Open access
Ko, Darae, Rahman, Faisal, Schnabel, Renate B., Yin, Xiaoyan, Benjamin, Emelia J., Christophersen, Ingrid E.·2016·Nature Reviews Cardiology
DOI 10.1038/nrcardio.2016.45PMC PMC5579870
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Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia in women and men worldwide. During the past century, a range of risk factors has been associated with AF, severe complications from the arrhythmia have been identified, and its prevalence has been increasing steadily. Whereas evidence has accumulated regarding sex-specific differences in coronary heart disease and stroke, the differences between women and men with AF has received less attention. We review the current literature on sex-specific differences in the epidemiology of AF, including incidence, prevalence, risk factors, and genetics, and in the pathophysiology and the clinical presentation and prognosis of patients with this arrhythmia. We highlight current knowledge gaps and areas that warrant future research, which might advance understanding of variation in the risk factors and complications of AF, and ultimately aid more-tailored management of the arrhythmia.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review summarizes sex differences in atrial fibrillation (AF) epidemiology, pathophysiology, presentation, and prognosis, noting lower incidence and prevalence in women but higher symptom burden, stroke risk, and some mortality risk. It highlights major knowledge gaps, especially limited pathophysiologic and non-North American/European data and lack of formal sex-interaction testing.

Key findings

  • AF prevalence is lower in women (373 per 100,000) than men (596 per 100,000); age-adjusted incidence in North America/Europe is 1.5–2 times higher in men, with Framingham and Olmsted County incidence rates of 1.6 and 2.7 per 1000 person-years in women versus 3.8 and 4.7 in men.
  • Lifetime risk is similar in North American/European populations (Framingham at age 60: 23.4% in women vs 25.8% in men; Rotterdam at age 55: 22.2% vs 23.8%), but a Chinese population study reported higher lifetime risk in women than men (22.2% vs 16.7%).
  • Women with AF are more likely to be symptomatic and less likely to have asymptomatic AF (RR 0.57; 95% CI 0.52–0.64), more often seek care, and have worse quality of life; female sex is an independent risk factor for AF-related stroke (e.g., Framingham HR 1.92, 95% CI 1.2–3.07; ATRIA RR 1.6, 95% CI 1.3–1.9).
  • Mortality findings are inconsistent across studies, but a meta-analysis of 19 studies found higher all-cause mortality in women than men with AF (women-to-men RR 1.12, 95% CI 1.07–1.17); sex differences in AF-related heart failure, myocardial infarction, and dementia remain less clear.

Methods

  • Design: narrative review of the literature on sex-specific differences in AF epidemiology, pathophysiology, clinical presentation, and prognosis.
  • Data/sample: published studies, including cohort, registry, randomized trial, and meta-analysis data, with supplementary tables; no primary patient sample was analyzed.
  • Main analysis: narrative synthesis of incidence, prevalence, risk factors, genetics, pathophysiology, presentation, and prognosis, with identification of knowledge gaps and future research directions.

Limitations

  • The authors state that studies investigating sex-related differences in AF pathophysiology are limited and mechanisms remain inadequately understood.
  • The authors state that many studies had limited sample size and did not formally test for effect modification by sex; data from outside North America and Europe are sparse, and findings may not generalize to other ethnic groups.
  • Evident from the text: as a narrative review, it does not report a systematic search strategy, inclusion criteria, or formal quality/risk-of-bias assessment; mortality comparisons are also challenged by substantial differences in follow-up time across studies.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/nrcardio.2016.45

Cites

178 of 178 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 143 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Age-adjusted prevalence of AF is lower in women than in men in North America and Europe.

    “Similarly to incidence, age-adjusted prevalence of AF has been reported to be lower in women than in men in North America and Europe (Figure 2) (Supplementary Tables S3 and S4).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [5] Schnabel, R. B. et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386, 154–162 (2015). source

      Not checked in the free run.

    • cites [18] Wilke, T. et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace 15, 486–493 (2013). source

      Not checked in the free run.

    • cites [19] Piccini, J. P. et al. Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries, 1993–2007. Circ. Cardiovasc. Qual. Outcomes 5, 85–93 (2012). source

      Not checked in the free run.

  • Findingcitation

    In North American and European populations, the age-adjusted incidence of AF is 1.5 to 2 times higher in men than in women.

    “In North American and European populations, the age-adjusted incidence of AF has been estimated to be 1.5 to 2 times higher in men than in women (Supplementary Tables S1 and S2).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [5] Schnabel, R. B. et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386, 154–162 (2015). source

      Not checked in the free run.

    • cites [15] Benjamin, E. J. et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 98, 946–952 (1998). source

      Not checked in the free run.

    • cites [1] Chugh, S. S. et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129, 837–847 (2014). source

      Not checked in the free run.

  • Findingcitation

    AF incidence increases disproportionately with increasing age in both women and men, reaching as high as 30.4 per 1000 person-years in women and 32.9 per 1000 person-years in men by age 85-89 years.

    “AF incidence has been shown to increase disproportionately with increasing age in both women and men, reaching as high as 30.4 per 1000 person-years in women and 32.9 per 1000 person-years in men by age 85–89 years.17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Chien, K. L. et al. Atrial fibrillation prevalence, incidence and risk of stroke and all-cause death among Chinese. Int. J. Cardiol. 139, 173–180 (2010). source

      Not checked in the free run.

  • Findingcitation

    Because women typically live longer than men, the absolute number of women exceeds the number of men with AF in Medicare data.

    “Because women typically live longer than men, the absolute number of women exceeds the number of men with AF in Medicare data.18”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Wilke, T. et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace 15, 486–493 (2013). source

      Not checked in the free run.

  • Findingcitation

    The estimated prevalence of AF is lower in women (373 per 100,000) than in men (596 per 100,000).

    “The estimated prevalence is lower in women (373 per 100,000) than in men (596 per 100,000).1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Chugh, S. S. et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129, 837–847 (2014). source

      Not checked in the free run.

  • May combine two claims. 22
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Findingcitation

    In women, AF is associated with worse symptoms and quality of life, and increased risk of complications such as stroke and mortality, compared with men.

    “in women, AF is associated with worse symptoms and quality of life,10–12 and increased risk of complications such as stroke13 and mortality,14 compared with men.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] Humphries, K. H. et al. New-onset atrial fibrillation: sex differences in presentation, treatment, and outcome. Circulation 103, 2365–2370 (2001). source

      Not checked in the free run.

    • cites [14] Bushnell, C. et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45, 1545–1588 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The lower AF incidence among women seems to be consistently observed outside North America and Europe, although fewer studies are available.

    “The lower AF incidence among women seems to be consistently observed outside North America and Europe, although fewer studies are available.1,16”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Chugh, S. S. et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 129, 837–847 (2014). source

      Not checked in the free run.

    • cites [16] Miyasaka, Y. 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 114, 119–125 (2006). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Among individuals with AF, women are more likely than men to experience symptoms and to seek care for these symptoms.

    “Studies indicate that among individuals with AF, women are more likely than men to experience symptoms,60,11,12 and to seek care for these symptoms.10,11”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [10] Ball, J., Carrington, M. J., Wood, K. A., Stewart, S. & Investigators, S. Women versus men with chronic atrial fibrillation: insights from the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY). PLoS ONE 8, e65795 (2013). source

      Not checked in the free run.

    • cites [11] Scheuermeyer, F. X. 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. 22, 1067–1075 (2015). source

      Not checked in the free run.

    • cites [12] 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. 191, 172–177 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In men, a U-shaped association has been reported between physical activity and AF, in which sedentary lifestyle and vigorous exercise both are associated with increased AF risk, whereas moderate activity is protective.

    “In men, a U-shaped association has been reported, in which sedentary lifestyle and vigorous exercise both are associated with increased AF risk,41,44,45 whereas moderate activity is protective.46”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [41] Larsson, S. C., Drca, N. & Wolk, A. Alcohol consumption and risk of atrial fibrillation: a prospective study and dose-response meta-analysis. J. Am. Coll. Cardiol. 64, 281–289 (2014). source

      Not checked in the free run.

    • cites [44] Aviles, R. J. et al. Inflammation as a risk factor for atrial fibrillation. Circulation 108, 3006–3010 (2003). source

      Not checked in the free run.

    • cites [45] Aizer, A. et al. Relation of vigorous exercise to risk of atrial fibrillation. Am. J. Cardiol. 103, 1572–1577 (2009). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In women, vigorous exercise has not been shown to increase AF risk, although moderate exercise is associated with a lower risk of AF than sedentary lifestyle.

    “In women, vigorous exercise has not been shown to increase AF risk, although moderate exercise is associated with a lower risk of AF than sedentary lifestyle.47,48”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [47] Mozaffarian, D., Furberg, C. D., Psaty, B. M. & Siscovick, D. Physical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study. Circulation 118, 800–807 (2008). source

      Not checked in the free run.

    • cites [48] Everett, B. M. et al. Physical activity and the risk of incident atrial fibrillation in women. Circ. Cardiovasc. Qual. Outcomes 4, 321–327 (2011). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Women with AF have higher prevalence of hypertension and valvular heart disease and lower prevalence of coronary heart disease than men with AF.

    “Women with AF have higher prevalence of hypertension and valvular heart disease and lower prevalence of coronary heart disease than men with AF.5,11,34”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [5] Schnabel, R. B. et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386, 154–162 (2015). source

      Not checked in the free run.

    • cites [11] Scheuermeyer, F. X. 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. 22, 1067–1075 (2015). source

      Not checked in the free run.

    • cites [34] Wang, T. J. et al. Obesity and the risk of new-onset atrial fibrillation. JAMA 292, 2471–2477 (2004). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Globally, the prevalence of valvular heart disease among individuals with AF is still greater than 25%, largely caused by the higher incidence of rheumatic heart disease in low-income and middle-income countries.

    “However, globally, the prevalence of valvular heart disease among individuals with AF is still greater than 25%,38,39 largely caused by the higher incidence of rheumatic heart disease in low-income and middle-income countries.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [38] Huxley, R. R. et al. Absolute and attributable risks of atrial fibrillation in relation to optimal and borderline risk factors: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 123, 1501–1508 (2011). source

      Not checked in the free run.

    • cites [39] Chiang, C. E. et al. Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice: insight from the real-life global survey evaluating patients with atrial fibrillation international registry. Circ. Arrhythm. Electrophysiol. 5, 632–639 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a population-based study from China, the lifetime risk for women at age 55 years was 22.2%, higher than that for men (16.7%).

    “A population-based study from China showed similar lifetime risk for women at age 55 years (22.2%); however, in contrast to North American populations, the lifetime risk for women in China was higher than that for men (22.2% versus 16.7%).31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Heeringa, J. et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur. Heart J. 27, 949–953 (2006). source

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingcitation

    Body mass index has increased significantly in both women and men with AF.

    “In particular, body mass index has increased significantly (Figure 3).5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] Schnabel, R. B. et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386, 154–162 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A genetic variant in the X-linked gene KCNE5 was more frequent in controls than in patients with AF and was found to be protective of AF.

    “In 2005, Ravn et al. discovered a genetic variant in the X-linked gene KCNE5 that was more frequent in 96 controls than in 158 patients with AF, and that was found to be protective of AF.57”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Lubitz, S. A. et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 304, 2263–2269 (2010). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Plasma concentrations of C-reactive protein and fibroblast growth factor-23 are higher in women than in men in epidemiological studies.

    “The plasma concentrations of the inflammatory marker C-reactive protein143 and of fibroblast growth factor-23144 have been found to be higher in women than in men in epidemiological studies.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [143] Wang, T. J. et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 107, 2920–2925 (2003). source

      Not checked in the free run.

    • cites [144] Miyasaka, Y. et al. Incidence and mortality risk of congestive heart failure in atrial fibrillation patients: a community-based study over two decades. Eur. Heart J. 27, 936–941 (2006). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Women generally have reduced ventricular wall thickness and smaller left atria and ventricles compared with men.

    “Women generally have reduced ventricular wall thickness and smaller left atria and ventricles compared with men.138–141”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [138] Horstmann, S. et al. Atrial fibrillation and prestroke cognitive impairment in stroke. J. Neurol. 261, 546–553 (2014). source

      Not checked in the free run.

    • cites [139] Bunch, T. J. et al. Atrial fibrillation is independently associated with senile, vascular, and Alzheimer's dementia. Heart Rhythm 7, 433–437 (2010). source

      Not checked in the free run.

    • cites [140] Dublin, S. et al. Atrial fibrillation and risk of dementia: a prospective cohort study. J. Am. Geriatr. Soc. 59, 1369–1375 (2011). source

      Not checked in the free run.

    • cites [141] Forti, P. et al. Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment (MCI). Arch. Gerontol. Geriatr. 44 (Suppl. 1), 155–165 (2007). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Both long and short PR intervals are associated with increased risk of AF in women, whereas only longer PR intervals are associated with AF in men.

    “the Copenhagen ECG Study showed that both long and short PR intervals were associated with increased risk of AF in women, whereas only longer PR intervals were associated with AF in men.159”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [159] Marijon, E. et al. Causes of death and influencing factors in patients with atrial fibrillation: a competing-risk analysis from the randomized evaluation of long-term anticoagulant therapy study. Circulation 128, 2192–2201 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    None of the genetic risk scores developed thus far have reported sex differences in AF prediction.

    “None of the genetic risk scores developed thus far have reported sex differences in AF prediction.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In a study of patients visiting the emergency department, women were more likely to have longer duration of symptoms and to present with atypical symptoms, such as weakness and fatigue.

    “In a study of patients visiting the emergency department, women were more likely to have longer duration of symptoms and to present with atypical symptoms, such as weakness and fatigue.11,12”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Scheuermeyer, F. X. 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. 22, 1067–1075 (2015). source

      Not checked in the free run.

    • cites [12] 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. 191, 172–177 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Women are more likely to seek care for symptoms, which might partly be attributable to higher mean heart rates at presentation.

    “Women seem to be more likely to seek care for symptoms, which might partly be attributable to higher mean heart rates at presentation.10,11”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Ball, J., Carrington, M. J., Wood, K. A., Stewart, S. & Investigators, S. Women versus men with chronic atrial fibrillation: insights from the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY). PLoS ONE 8, e65795 (2013). source

      Not checked in the free run.

    • cites [11] Scheuermeyer, F. X. 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. 22, 1067–1075 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In a rabbit model, left atrial and pulmonary vein tissue from females displayed longer action potential duration, and female pulmonary vein tissue had a more negative resting membrane potential compared with males.

    “In a rabbit model, left atrial and pulmonary vein tissue from females displayed longer action potential duration, and female pulmonary vein tissue had a more negative resting membrane potential compared with males.147”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [147] Stewart, S., Hart, C. L., Hole, D. J. & McMurray, J. J. V. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study. Am. J. Med. 113, 359–364 (2002). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Multiple longitudinal studies have evaluated whether an interaction exists between sex and AF-related risk of mortality, but the results have not been consistent.

    “Multiple longitudinal studies have evaluated whether an interaction exists between sex and AF-related risk of mortality, but the results have not been consistent (Supplementary Table S10).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [14] Bushnell, C. et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45, 1545–1588 (2014). source

      Not checked in the free run.

    • cites [72] Nattel, S., Burstein, B. & Dobrev, D. Atrial remodeling and atrial fibrillation: mechanisms and implications. Circ. Arrhythm. Electrophysiol. 1, 62–73 (2008). source

      Not checked in the free run.

    • cites [108] Clayton, J. A. & Collins, F. S. Policy: NIH to balance sex in cell and animal studies. Nature 509, 282–283 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A study from Groningen, Netherlands found that AF is an independent risk factor for new-onset heart failure with preserved ejection fraction in women, but not in men.

    “A study from Groningen, Netherlands found that AF is an independent risk factor for new-onset HF with preserved ejection fraction in women, but not in men.98”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Stramba-Badiale, M., Locati, E. H., Martinelli, A., Courville, J. & Schwartz, P. J. Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. Eur. Heart J. 18, 1000–1006 (1997). source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The bulk of studies evaluating sex differences in the AF-related risk of heart failure have showed no significant difference; however, a few studies have suggested higher risk in women.

    “The bulk of studies evaluating sex differences in the AF-related risk of HF have showed no significant difference; however, a few studies have suggested higher risk in women (Supplementary Table S8).”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [97] Liu, X. K. et al. Gender difference in the cycle length-dependent QT and potassium currents in rabbits. J. Pharmacol. Exp. Ther. 285, 672–679 (1998). source

      Not checked in the free run.

    • cites [98] Stramba-Badiale, M., Locati, E. H., Martinelli, A., Courville, J. & Schwartz, P. J. Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. Eur. Heart J. 18, 1000–1006 (1997). source

      Not checked in the free run.

    • cites [99] Nielsen, J. B. et al. Risk of atrial fibrillation as a function of the electrocardiographic PR interval: results from the Copenhagen ECG Study. Heart Rhythm 10, 1249–1256 (2013). source

      Not checked in the free run.

    • cites [100] Cheng, S. et al. Long-term outcomes in individuals with prolonged PR interval or first-degree atrioventricular block. JAMA 301, 2571–2577 (2009). source

      Not checked in the free run.

    • cites [101] Buitrago, C., Massheimer, V. & de Boland, A. R. Acute modulation of Ca2+ influx on rat heart by 17β-estradiol. Cell. Signal. 12, 47–52 (2000). source

      Not checked in the free run.

    • cites [102] Jovanovic, S., Jovanovic, A., Shen, W. K. & Terzic, A. Low concentrations of 17β-estradiol protect single cardiac cells against metabolic stress-induced Ca2+ loading. J. Am. Coll. Cardiol. 36, 948–952 (2000). source

      Not checked in the free run.

    • cites [103] Magnani, J. W. et al. Association of sex hormones, aging, and atrial fibrillation in men: the Framingham Heart Study. Circ. Arrhythm. Electrophysiol. 7, 307–312 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Elevated body mass index, hypertension, diabetes mellitus, coronary heart disease, valvular heart disease, and heart failure are major risk factors for AF, but their prevalence varies between women and men.

    “Elevated body mass index, hypertension, diabetes mellitus, coronary heart disease, valvular heart disease, and heart failure (HF) constitute major risk factors for AF, but the prevalence of these risk factors vary between women and men.3–5”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Tedrow, U. B. et al. The long- and short-term impact of elevated body mass index on the risk of new atrial fibrillation the WHS (women's health study). J. Am. Coll. Cardiol. 55, 2319–2327 (2010). source

      Not checked in the free run.

    • cites [4] Benjamin, E. J. et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 271, 840–844 (1994). source

      Not checked in the free run.

    • cites [5] Schnabel, R. B. et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386, 154–162 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In North American populations, despite higher incidence of AF in men, lifetime risk of AF in women and men is similar owing to longer life expectancy for women.

    “In North American populations, despite higher incidence of AF in men, lifetime risk of AF in women and men were similar owing to longer life expectancy for women.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Majeed, A., Moser, K. & Carroll, K. Trends in the prevalence and management of atrial fibrillation in general practice in England and Wales, 1994–1998: analysis of data from the general practice research database. Heart 86, 284–288 (2001). source

      Not checked in the free run.

    • cites [30] Lloyd-Jones, D. M. et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110, 1042–1046 (2004). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Advancing age is the most important risk factor for AF, leading to about a doubling in AF incidence with every 10-year increase in age.

    “Advancing age is the most important risk factor, leading to about a doubling in AF incidence with every 10-year increase in age.4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Benjamin, E. J. et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 271, 840–844 (1994). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The KCNE5 variant might contribute to the lower prevalence of AF in women because women have two copies of the X chromosome whereas men have one.

    “Since women have two copies of the X chromosome whereas men have one, the investigators suggested that the variant might contribute to the lower prevalence of AF in women.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Lubitz, S. A. et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 304, 2263–2269 (2010). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Sex differences in hormones and in electrical and structural characteristics might help explain variation in incidence, prevalence, burden, and complications associated with AF in women and men.

    “The reported literature suggest that sex differences in hormones and in electrical and structural characteristics might help explain variation in incidence, prevalence, burden, and complications associated with AF in women and men.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The AF-related sex differences in epidemiology, risk factors, and outcomes identified in populations of European ancestry might not be generalizable to other ethnic groups.

    “The AF-related sex differences in epidemiology, risk factors, and outcomes identified in populations of European ancestry might not be generalizable to other ethnic groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The meta-analysis included disease-based samples and the results might thus not be generalizable to the general population.

    “Notably, the meta-analysis included disease-based samples and the results might thus not be generalizable to the general population.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [120] Friberg, J., Scharling, H., Gadsboll, N., Truelsen, T. & Jensen, G. B. 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. 94, 889–894 (2004). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Although the pathophysiology of AF has been investigated extensively, our understanding of the differences between male and female cardiac anatomy and electrical mechanisms is insufficient.

    “Although the pathophysiology of AF has been investigated extensively through the years,170 our understanding of the differences between male and female cardiac anatomy and electrical mechanisms, which might contribute to difference in risks and prognosis of AF by sex, is insufficient.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [170] Nattel, S. New ideas about atrial fibrillation 50 years on. Nature 415, 219–226 (2002). source

      Not checked in the free run.

28 of 28

  • The paper relies on this without support.

    AF is the most common sustained arrhythmia in women and men worldwide.

    “Atrial fibrillation (AF) is the most common sustained arrhythmia in women and men worldwide.”

  • The paper relies on this without support.

    Little is known about the underlying mechanisms of the increased risk of stroke in women with atrial fibrillation.

    “Nonetheless, little is known of the underlying mechanisms.”

  • The paper relies on this without support.

    Little attention has been paid to potential sex differences in the atrial fibrillation-related risks of heart failure, myocardial infarction, and dementia.

    “To date, little attention has been paid to potential sex differences in the AF-related risks of HF, MI, and dementia.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Sex-specific CHA2DS2-VASc scores are reversed

    Minor

    The paper first assigns a score of 0 to men and 1 to women in the MI analysis, then assigns scores of 0 and 1 to women and men, respectively. The latter also conflicts with the paper's statement that female sex itself earns one point.

  • Reported hazard ratio lies outside its confidence interval

    Minor

    The reported Swedish hazard ratio of 1.18 is above the upper bound of its reported 95% confidence interval, 1.15.

2 of 2

Cites

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Cited by

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Related

Authors
Ko, D., Rahman, F., Schnabel, R. B., Yin, X., Benjamin, E. J., & Christophersen, I. E.
Affiliations
  • Boston University (US)
  • Universität Hamburg (DE)
  • Vestre Viken Hospital Trust (NO)
Corresponding author
Christophersen, Ingrid E.
ORCID
Venue
Nature Reviews Cardiology
Publisher
Springer Science and Business Media LLC
Published
2016-04-07
Volume
13
Issue
6
Pages
321-332
ISSN
  • 1759-5002 (ISSN-L)
  • 1759-5010
DOI
10.1038/nrcardio.2016.45
PMC
PMC5579870
OpenAlex
W2322257236
Semantic Scholar
1d4b97cb3df2f8a8056dfdb009b6158ca5720889
Cited by
353
References
178
Citations by year
2026: 29 · 2025: 43 · 2024: 41 · 2023: 37 · 2022: 43 · 2021: 40 · 2020: 37 · 2019: 27 · 2018: 26 · 2017: 20 · 2016: 9
FWCI
4.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR000157, n01hc25195-41-0-1)
  • National Heart, Lung, and Blood Institute (HHSN268201500001I, HHSN268201500001C, R01HL128914, R01HL102214, T32HL007224, N01-HC-025195, RC1HL101056, R01HL092577)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
atrial fibrillation, sex differences, women, epidemiology, pathophysiology, risk factors, clinical features, prognosis, arrhythmia complications
MeSH terms
Atrial Fibrillation, Female, Humans, Prognosis, Risk Factors, Sex Factors, Incidence, Prevalence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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