The Global Impact of Atrial Fibrillation

Abstract

AF is a common yet multifaceted cardiac arrhythmia with a far-reaching impact. The global burden of AF has been growing rapidly over the last few decades, partly related to the increasing overall burden of chronic illnesses in the setting of an ageing world population. Not only is AF common, but it also has significant implications for patients’ health. There exist regional variations in the incidence, prevalence, morbidity and mortality of AF. Moreover, treatment strategies differ appreciably by global regions in a pattern influenced by regional differences in access to medications, the development of large-volume centres and the presence of clinical research. This review explores how AF epidemiology has evolved over time with distinct geographic heterogeneity, and it aims to provide an updated context for the global impact of AF.

AF is the most common sustained cardiac arrhythmia. The hallmark of AF is irregular atrial activity arising from ectopic re-entrant circuits near the pulmonary vein antra.1,2 Electrical and structural remodelling, fibrosis or scar formation and varying adrenergic or parasympathetic tone can all contribute to mechanisms that initiate and sustain AF.3 It has a multifactorial and complex pathophysiology that is heavily influenced by medical comorbidities, including obesity, the presence of heart failure, age, male sex, ethnicity, hypertension, diabetes, tobacco/alcohol use and a sedentary lifestyle.4

An estimated 52.55 million individuals are affected by AF and atrial flutter (AFL) worldwide as of 2021, representing a 137% increase from 1990.5 Based on data from the Framingham Heart Study, there is a 25% lifetime risk for developing AF in both men and women aged over 40 years.6 The burden of AF and AFL is anticipated to rise and affect over 8 million individuals in the US by 2050 and anywhere between 8.8 million and 18 million in Europe by 2060.7,8 Some projections estimate that the number of individuals living with AF in Africa will exceed that in either China, the US or India by 2050.9,10 The growing prevalence of AF can be attributed to multiple factors, including the rising degree of patient comorbidities, ageing populations and increased detection. AF harbours significant morbidity and mortality, conferring a 1.5–2-fold increased risk of death.1,11,12 Adverse outcomes associated with AF include its increased risk of stroke, dementia, MI, sudden cardiac death, heart failure, chronic kidney disease and peripheral arterial disease.1

The epidemiology of AF has evolved over time, reflecting changes in global populations. In this review, we will characterise what is known about the global burden of AF. We will discuss both the prevalence and incidence of AF by region and explore the demographics of affected patient populations. We will investigate how treatments vary by region and distinguish the varying influence of AF on morbidity and mortality. Our hope is to provide an updated context for the state of AF globally to better inform our treatment efforts for this important arrhythmia.

Incidence and Prevalence of AF

The most recent studies analysing global trends in AF were conducted by Cheng et al., who characterised the epidemiology of AF through 2021 using data from the 2021 Global Burden of Disease (GBD) Study, Li et al., who analysed AF data from GBD 2019 and Roth et al., who analysed data regarding all cardiovascular diseases and risk factors from the GBD 2019 study.5,13,14 Another large study characterising the worldwide epidemiology of AF was conducted by Chugh et al., based on data from 2010.15

Global Incidence and Prevalence

The global age-standardised incidence rate (ASIR) and age-standardised prevalence rate (ASPR) organised by sex and age from 1990 to 2021 are summarised in Figures 1 and 2, derived from data published by Cheng et al.5 Globally, there were ~4.5 million incident cases of AF/AFL in 2021 compared with 2 million in 1990. The absolute prevalence ofAF has nearly doubled in the last 30 years, from 22.2 million in 1990 to 52.5 million in 2021.5 AF burden is consistently higher for men compared with women. Chugh et al. reported higher age-adjusted incidence rates of 60.7 per 100,000 individuals in men compared with 43.8 in women in 1990;15 data reported by Cheng et al. demonstrate that this trend has persisted over time (Figure 1). However, while the absolute burden of AF is increasing worldwide, there has been relative stability in global age-adjusted incidence and prevalence rates (Figure 1). The global ASIR in 1990 was 52.51 per 100,000 individuals compared with 52.12 in 2021, with ASPR at 616.58 per 100,000 individuals in 1990 compared with 620.51 in 2021.5 The GBD 2019 study similarly found that prevalence rates have remained largely the same over time.13,14 The relative stability in age-standardised metrics suggests that the growing absolute burden ofAF worldwide might reflect an ageing population exposed to an increasing degree of comorbidities and chronic illnesses.16 Both incidence and prevalence rise significantly with increasing age (Figure 2). The absolute incidence of AF/AFL was highest in the global age category 70–74 years in 2021 at 744,978 cases; the age category 55–59 years saw the greatest annual percentage change in ASIR of ~22%.5 The absolute prevalence of AF was found to be highest among individuals aged 90–94 years, with an ASPR of 11,828 per 100,000.

Figure 1: Global Epidemiology of AF in 1990 Compared With 2021.

Data are organised by females, males and globally. Age-standardised incidence rate and age-standardised prevalence rate are reported per 100,000 individuals. Data source: Cheng et al. 2024. 5

Figure 2: Global Trends in Incidence and Prevalence Rates by Age Group from 1990 to 2021.

Incidence is reported as age-standardised incidence rate and prevalence is reported as age-standardised prevalence rate. Data source: Cheng et al. 2024. 5

Disparities by Continents and Countries

The epidemiology of AF can vary by 12-fold between regions.17 Excellent data published by Cheng et al. are shown in the world maps in Figure 3.5 Their data, organised by GBD-defined regions of the world, are shown in Figures 4 and 5. North America, Australasia and western Europe consistently had the highest incidence rates of AF/AFL, with ASIRs in 2021 of 88.23, 73.34 and 68.19 per 100,000, respectively (Figure 4).5 In 2021, the overall ASIR in Africa was 39.67 per 100,000 persons and 46.69 in Asia. Similarly, the highest ASPR was found in North America (1,031.09 per 100,000), Australasia (913.63) and western Europe (745.07), compared with Africa (432.2), Asia (529.04) and Middle East and North Africa (430.42) (Figure 5). Interestingly, the highest increase in incidence and prevalence of AF since 1990 has been seen in the United Arab Emirates, Qatar and Jordan.5

Figure 3: World Map of Age-standardised Incidence and Prevalence Rates in 2021.

ASIR per 100,000 in blue; ASPR per 100,000 in orange. ASIR = age-standardised incidence rate; ASPR = age-standardised prevalence rate. Source: Cheng et al. 2024. 5

Figure 4: Age-standardised Incidence Rate Per 100,000 by Global Region.

Source: Cheng et al. 2024. 5

Figure 5: Age-standardised Prevalence Rate Per 100,000 by Global Region.

Source: Cheng et al. 2024. 5

The epidemiology of AF is particularly influenced by socio-demographic index (SDI). Chugh et al. divided the world into ‘developed’ and ‘developing’ countries, which were determined by categorisations in the World Bank Atlas in 2010. In their analysis, incidence rates have always been higher in developed countries. For example, in 1990 the incidence rate for AF among men was 78.4 per 100,000 person-years in developed countries compared with 50.0 in developing countries, which rose to 123.4 and 53.8, respectively, by 2010.15 In the more recent analysis by Cheng et al., regions were defined by the more updated five categorisations of SDI (high, high-middle, middle, low-middle and low).5 Similarly, incidence rates demonstrated a stepwise increase with higher SDI. In 2021, incidence of AF/AFL was estimated at 65.1 per 100,000 in high SDI countries, 51.11 in middle SDI countries and 43.25 in low SDI countries.5 Prevalence statistics display the same trend. Age-adjusted prevalence rates in 2010 for men were 660.9 per 100,000 versus 565.7 in developed and developing countries, respectively, and for women were 387.7 versus 366.1.15 Data from 2021 estimated that prevalence was lowest in low SDI countries at 463.23 compared with 788.35 per 100,000 individuals in high SDI countries.5

These geographically disparate findings can be attributed to several factors. Limited data might be available in countries with lower SDI that lack robust medical systems, which may skew our understanding of the true distribution of AF in these communities. Differences in comorbidity burden may also impact regional variations in AF. A recent study specifically found a higher cumulative risk for developing AF in white Europeans compared with Korean populations, and that this increased risk was closely associated with higher BMI and smoking.18 High systolic blood pressure has been a leading risk factor attributed to burden of AF; in higher SDI countries, this is closely followed by high BMI, while in lower SDI countries this is closely followed by environmental risks.5 However, in a study investigating CHARGE-AF risk factors in the context of global epidemiology, traditional risk factors only accounted for <20% of the global variation in AF prevalence.17 In the same study, China and Southeast Asia appeared to have some of the highest prevalence rates of AF without having the same comorbidities and risk factors as North America and Europe, suggesting additional contributing factors including dietary habits or environmental risk.19,20 Geographic heterogeneity may additionally be related to genetic variation. A recent study of the AF-susceptibility allele KCNQ1 has traced ancestral inheritance to western Europe, northeastern US and midwestern US, suggesting genetics could represent an important risk factor with geographic implications.21

The Global Impact of AF

Most epidemiological studies have additionally characterised morbidity, mortality and disability-adjusted life years (DALY) estimates. One DALY represents the loss of 1 year of full health; it is calculated by adding number of years lost from premature mortality with years lived with disability due to the medical illness.

Overall, total mortality related to AF has been increasing over time; however, age-adjusted mortality and age-adjusted DALYs have remained somewhat comparable and vary based on the study. In the analysis by Chugh et al., age-adjusted mortality has been increasing since 1990, from 0.8 for men and 0.9 for women to 1.7 and 1.9, respectively, for men and women in 2010.15 Similarly, age-adjusted DALYs per 100,000 individuals were 54.3 and 38.6 in 1990 for men and women, compared to 64.5 and 45.9 in 2010 for men and women, respectively.15 In 2019 GBD data analyses, while there was an estimated increase in AF/AFL deaths by 169% from 1990 to 2019 despite a 45% growth in the global population, age-adjusted mortality has remained comparable.13 The total number of DALYs was quantified by Roth et al. and estimated at 8.39 million in 2019 compared with 3.79 million in 1990.14 Interestingly, Roth et al. also found that the age-adjusted DALYs and death rates did not display significant changes between 1990 and 2019.14

Higher SDI did not protect against deaths and DALYs; in fact, several high SDI countries, including China, US, Germany and Japan, were carrying a significant portion of global AF/AFL deaths. Data from the 2021 GBD data analysis have shown that age-adjusted DALYs were higher in upper SDI countries. Specifically, China, India, and the US had the highest DALYs, and China, India, and Germany had the most deaths.5 However, the change in DALYs over time has started to decline in high and high-middle SDI countries, while age-adjusted DALYs continue to rise in low, low-middle and middle SDI countries.5 Percent-change in DALYs and all-age mortality has an inverted U-shape across SDIs, with the greatest percentchange and increase in mortality in middle-SDI and low-middle SDI regions.13 GBD 2019 data also suggest a moderately decreasing net drift of AF/AFL mortality that is thought to be related to improved medical care in high-middle SDI and high SDI regions.13

Global Heterogeneity in the Treatment and Management of AF

There is significant variation in how AF is managed worldwide, partly related to disparities in health systems, resources, research and comorbidities.

Prior to the introduction of direct oral anticoagulants, practices regarding anticoagulation for AF varied significantly. In a 2014 global study characterising the use of oral anticoagulation in patients with AF presenting to the emergency department in 46 countries, 65.7% of patients with CHADS₂ ≥2 in North America were on oral anticoagulation, 63.2% of patients in western Europe and 11.2% of patients in China.22 Rates in other regions fluctuated widely, ranging from 11.0% to 56%. In a study comparing low-, middle- and high-income countries, the proportion of patients with CHADS₂ score >1 was similar at around 70% of patients; however, 85% of patients in high-income countries were receiving antiplatelet or warfarin therapy compared with 24% of patients in either middle-income or low-income countries.17 Reasons that were cited for the large gap between countries included concerns regarding warfarin-related intracranial haemorrhage and disagreement regarding appropriate therapeutic international normalised ratio ranges. Additionally, AF related stroke risk may vary by region and by country, with some studies reporting decreased risk of ischaemic stroke and haemorrhage in healthy Asian patients without AF when compared with similar white patients.23,24 However, in a Korean analysis of AF and stroke burden, it was reported that Asian patients with AF were found to have a numerically higher incidence of ischaemic stroke in subgroup analyses of major clinical trials, although statistical significance was not reported.25 One study applied a modified CHA₂DS₂-VASc score to Asian patients and found that adjusting the score to include 1 point for age 50–74 performed better.26

Nevertheless, the implementation of anticoagulation has evolved worldwide with the introduction of newer anticoagulants. In a study conducted after the wider spread implementation of non-vitamin K antagonist oral anticoagulants, the global proportion of patients prescribed oral anticoagulation almost doubled from 42% of patients in 2010 to 78% of patients in 2018.27 There remains wide variation in the implementation of stroke prevention in many countries due to lack of access. In epidemiological studies in Africa, many anticoagulants are not available and, if prescribed, follow-up is variable.28 In one study in subSaharan Africa, the implementation of anticoagulation varied widely from 8.8% in Nigeria to 79.7% of patients in Burkina Faso.29

There are fewer data on current trends for catheter ablation globally. In the US, pulmonary vein isolation makes up ~20% of all ablation procedures.30 AF ablation volume increased to 111.6 per 100,000 patientyears in 2021 in the US.31 In Europe, it was estimated that approximately 100,000 out of 600,000 patients with AF undergo ablation.32 Centre volume of ablation procedures impacts the procedural success and efficacy of ablation, which can additionally influence treatment practices by region. In an analysis of the AF ablation registry in Europe, it was suggested that a centre should perform >74 ablations per year in order to have overall favourable outcomes.33 In a study of 76,219 patients across 162 hospitals in the US between 2016 and 2020, the median hospital volume was 130 procedures annually, with a reported average acute procedural success rate of 92.4% and complication rate of 2.5%.34

In a more recent study across 186 hospitals in the US through 2022, the median hospital procedural volume was 230, with an acute success rate of 98.5%; rates of major adverse events and adverse events were even lower, at 1% and 2.2%, respectively.35 In this study, hospital volume similarly correlated with improved acute procedural success and outcomes. An adjusted procedural major adverse event rate of <1% was predicted by annual hospital volume of 190 and annual physician volume of 60.35 Catheter ablation may also be a more cost-effective strategy when compared with medical management for rhythm control. In a recent study of real-world data derived from primarily the UK and US, catheter ablation was found to be highly cost-effective and with greater clinical benefit.36

In a report from the Asia Summit, AF ablation practices vary widely throughout Asia, with Japan and New Zealand performing the most ablation procedures per million (~600 per million in Japan and ~100 per million in New Zealand), followed by South Korea (~100 per million), Brunei Darussalam (~100 per million), China (~50 per million), Taiwan (<50 per million) and Singapore (<50 per million).37 In Africa, access to ablation is more limited. Only 22% of countries in Africa offer services for simple ablation procedures.10,28,29 Cryoablation was reported to be available in only a handful of countries, including Algeria, Egypt, Morocco, Namibia, South Africa and Tunisia.10 In data from 33 of 55 countries in Africa, five countries (15%) lacked a single cardiologist and 18 (54%) lacked a single electrophysiology laboratory.10,38 Interestingly, the most commonly used agents for rate and rhythm control in these regions were digoxin and amiodarone.10 Limitations for adequate access to treatments for cardiac arrhythmias generally have included lack of government support, lack of national health insurance, a paucity of adequate facilities and trained practitioners, high cost of treatments and low levels of clinical research.10

Conclusion

The global burden of AF continues to grow. The highest incidence and prevalence rates are found in North America, western Europe, East Asia, and Australia/New Zealand; however, data are more limited in Africa and South America. Total morbidity and mortality are climbing but overall age-adjusted annual rates have remained stable, reflecting the consequences of an ageing world population. Treatment practices can vary widely by region, partly because of differences in research, centre experience with ablation procedures and access to medications and trained practitioners. AF remains a widespread and complex arrhythmia whose global impact is far-reaching.

Clinical Perspective

• The global burden of AF has significantly increased with time.

• Age-adjusted incidence and prevalence rates have remained stable, suggesting that the growing burden of AF may be attributable to ageing populations exposed to increasing comorbidities.

• Countries and regions with the highest recorded incidence and prevalence of AF include the US, western Europe, Australia and east Asia.

• Treatment for AF has significant geographic heterogeneity, influenced by regional resources, research and varying comorbidity burden.