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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“The lower AF incidence among women seems to be consistently observed outside North America and Europe, although fewer studies are available.1,16”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [44] Aviles, R. J. et al. Inflammation as a risk factor for atrial fibrillation. Circulation 108, 3006–3010 (2003). source
• Not checked yetcites [45] Aizer, A. et al. Relation of vigorous exercise to risk of atrial fibrillation. Am. J. Cardiol. 103, 1572–1577 (2009). source

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [34] Wang, T. J. et al. Obesity and the risk of new-onset atrial fibrillation. JAMA 292, 2471–2477 (2004). source

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [31] Heeringa, J. et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur. Heart J. 27, 949–953 (2006). source

In the paper

“In particular, body mass index has increased significantly (Figure 3).5”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [57] Lubitz, S. A. et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 304, 2263–2269 (2010). source

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“Women generally have reduced ventricular wall thickness and smaller left atria and ventricles compared with men.138–141”

What the sources say

• Not checked yetcites [138] Horstmann, S. et al. Atrial fibrillation and prestroke cognitive impairment in stroke. J. Neurol. 261, 546–553 (2014). source
• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [108] Clayton, J. A. & Collins, F. S. Policy: NIH to balance sex in cell and animal studies. Nature 509, 282–283 (2014). source

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [30] Lloyd-Jones, D. M. et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110, 1042–1046 (2004). source

In the paper

“Advancing age is the most important risk factor, leading to about a doubling in AF incidence with every 10-year increase in age.4”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [57] Lubitz, S. A. et al. Association between familial atrial fibrillation and risk of new-onset atrial fibrillation. JAMA 304, 2263–2269 (2010). source

In the paper

“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.”

In the paper

“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.”

In the paper

“Notably, the meta-analysis included disease-based samples and the results might thus not be generalizable to the general population.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [170] Nattel, S. New ideas about atrial fibrillation 50 years on. Nature 415, 219–226 (2002). source