Arrhythmia/Electrophysiology
`
`Worldwide Epidemiology of Atrial Fibrillation
`A Global Burden of Disease 2010 Study
`
`Sumeet S. Chugh, MD; Rasmus Havmoeller, MD, PhD; Kumar Narayanan, MD;
`David Singh, MD; Michiel Rienstra, MD, PhD; Emelia J. Benjamin, MD, ScM;
`Richard F. Gillum, MD; Young-Hoon Kim, MD; John H. McAnulty, Jr, MD;
`Zhi-Jie Zheng, MD, PhD; Mohammad H. Forouzanfar, MD; Mohsen Naghavi, MD;
`George A. Mensah, MD; Majid Ezzati, PhD; Christopher J.L. Murray, MD
`
`Background—The global burden of atrial fibrillation (AF) is unknown.
`Methods and Results—We systematically reviewed population-based studies of AF published from 1980 to 2010 from
`the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality
`related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The
`estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval
`(UI), 19.5–22.2 million] and 12.6 million women [95% UI, 12.0–13.7 million]). Burden associated with AF, measured
`as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8–19.3) in men and 18.9% (95% UI, 15.8–23.5) in
`women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were
`569.5 in men (95% UI, 532.8–612.7) and 359.9 in women (95% UI, 334.7–392.6); the estimated age-adjusted incidence
`rates were 60.7 per 100 000 person-years in men (95% UI, 49.2–78.5) and 43.8 in women (95% UI, 35.9–55.0). In 2010,
`the prevalence rates increased to 596.2 (95% UI, 558.4–636.7) in men and 373.1 (95% UI, 347.9–402.2) in women;
`the incidence rates increased to 77.5 (95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9) in women. Mortality
`associated with AF was higher in women and increased by 2-fold (95% UI, 2.0–2.2) and 1.9-fold (95% UI, 1.8–2.0)
`in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF
`estimations and availability of population-based data.
`Conclusions—These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and
`AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional
`surveillance of AF is required to better direct prevention and treatment strategies. (Circulation. 2014;129:837-847.)
`Key Words: atrial fibrillation ◼ epidemiology ◼ incidence ◼ prevalence ◼ risk factors, prevention
`
`Atrial fibrillation (AF) is the most common arrhythmia of
`
`clinical significance.1 In adjusted models, AF is associated
`with increased morbidity, especially stroke and heart failure, and
`increased mortality.2–5 AF constitutes a significant public health
`problem, and estimates suggest that this condition accounts
`for 1% of the National Health Service budget in the United
`Kingdom6 and $16 to 26 billion of annual US expenses.7,8
`Editorial see p 829
`Clinical Perspective on p 847
`
`Several regional studies suggest a rising prevalence and
`incidence of AF.9–13 These secular trends may be explained
`in part by the demographic transition to an inverted age pyra-
`mid because frequency of AF increases with advancing age.
`Others have demonstrated an increase in AF incidence after
`age adjustment, which is probably a reflection of comorbidities
`and cardiovascular risk factors, in addition to other factors such
`as lifestyle changes.14,15 In the United States, it is estimated that
`the number of adults with AF will more than double by the year
`2050;16 even higher increases have been predicted.14
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`
`Received July 22, 2013; accepted November 12, 2013.
`From the Cedars-Sinai Heart Institute, Los Angeles, CA (S.S.C., R.H., K.N., D.S.); Karolinska Institute, Stockholm, Sweden (R.H.); University of
`Groningen, University Medical Center Groningen, Groningen, the Netherlands (M.R.); Framingham Heart Study and Boston University School of Medicine
`and Public Health, Boston, MA (E.J.B.); Department of Medicine, Howard University College of Medicine, Washington, DC (R.F.G.); Korea University
`College of Medicine, Seoul, Republic of Korea (Y.-H.K.); Legacy Good Samaritan Medical Center, Portland, OR (J.H.M.); National Heart, Lung, and
`Blood Institute, Bethesda, MD (Z.-J.Z., G.A.M.); Institute for Health Metrics and Evaluation, University of Washington, Seattle (M.H.F., M.N., C.J.L.M.);
`and Harvard School of Public Health, Boston, MA (M.E.).
`Guest Editor for this article was Mercedes Carnethon, PhD.
`The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIRCULATIONAHA.
`113.005119/-/DC1.
`Correspondence to Sumeet S. Chugh, MD, The Heart Institute, AHSP Ste A3300, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles,
`CA 90048. E-mail sumeet.chugh@cshs.org
`© 2013 American Heart Association, Inc.
`Circulation is available at http://circ.ahajournals.org
`
`837
`
`DOI: 10.1161/CIRCULATIONAHA.113.005119
`BMS 2003
`MYLAN v. BMS
`IPR2018-00892
`
`

`

`a final list of publications selected for abstraction. Each publication
`was assigned to 1 of 21 epidemiological regions as designated in
`GBD 2005. To minimize potential bias resulting from inconsistent
`case definitions of AF, all published studies of paroxysmal, persistent,
`or permanent/chronic AF and atrial flutter were included.
`
`Statistical Methods
`Incidence rate was defined as the annual number of new cases with
`AF divided by the population at midyear. Prevalence rate was defined
`as the overall number of cases with the total population as denomi-
`nator. Prevalence and incidence rates were age adjusted. Rates were
`presented per 100 000 persons or person-years with 95% uncertainty
`intervals (UIs). The denominators were derived from the United
`Nations population database (http://www.un.org/esa/population/),
`and classifications of countries, regions, and groups (eg, developed
`and developing countries) followed the definitions of the World Bank
`(http://data.worldbank.org/about/country-classifications) and GBD
`core team decisions.22
`
`Modeling of AF as a Cause of Death
`Mortality associated with AF was estimated by use of an integrated
`method, with information on several country-level covariates used
`to inform the analysis.19 All combinations of the covariates with a
`significant coefficient (P<0.05) and expected direction of the effect
`were used to estimate the number of deaths. The performance of each
`model in terms of external validity was evaluated and constituted the
`final ensemble model estimate. External validity criteria were used
`to rank all models and to produce ensemble results.23 The covariates
`and external validity of the ensemble model are reported in Appendix
`IV (Tables I and II in the online-only Data Supplement). In the next
`step, each individual cause of death was adjusted to obtain overall
`cardiovascular mortality (CoDCorrect process).19 The GBD method
`provides the mortality rate attributable to AF as opposed to total case
`fatality rate in AF patients.
`
`Modeling of Morbidity Associated With AF
`We used incidence, prevalence, excess mortality, and AF mortality
`rate (estimated by the CODEm process) in a bayesian meta-regression
`tool (DisMod-MR: Figure 1).21,24 DisMod-MR estimates a general-
`ized negative binomial model for all the epidemiological data with
`fixed and random effects. Data modeled with fixed effects include
`age, covariates that predict country variation in the quantity of inter-
`est, variation across studies resulting from attributes of the study
`protocol, and random effects of super-region, region, and country.
`DisMod-MR can be used to estimate age-, sex-, and country-specific
`prevalence from heterogeneous and often sparse data sets. We used
`
`838
`
` Circulation
`
` February 25, 2014
`
`In view of the emergence of AF as a growing epidemic,15,17
`an assessment of the global burden of AF is warranted. We
`therefore conducted a comparative assessment of the burden
`of AF across defined time periods based on available epide-
`miological data from the 21 Global Burden of Disease (GBD)
`regions.
`
`Methods
`
`The GBD Study
`Our analysis was performed within the framework of the latest Global
`Burden of Disease, Injuries, and Risk Factors Study (GBD 2010
`Study).18 The GBD 2010 Study is a collaborative effort led by a consor-
`tium that includes Harvard University, the Institute for Health Metrics
`and Evaluation at the University of Washington, Johns Hopkins
`University, the University of Queensland, the University of Tokyo,
`Imperial College London, and the World Health Organization. It follows
`on the original GBD 1990 Study commissioned by the World Bank in
`1991 and aims to systematically assess global data on all diseases and
`injuries. GBD 2010 provides a common instrument for assessing mor-
`tality and morbidity. The goal was to provide comparable estimates at
`different time periods with analysis of secular trends. Detailed informa-
`tion about the data, techniques, and methods for estimation of different
`disease parameters has been published elsewhere.19–21
`
`Search Strategy and Data Sources
`As a subcommittee of the GBD 2010 Committee on Cardiovascular
`Disease and following the GBD 2010 protocol, the GBD Arrhythmias
`Panel performed a systematic review of the available literature
`(Appendix I in the online-only Data Supplement) to identify epidemi-
`ological studies of AF (1980–2010) that were population based. For
`the initial identification of published studies, we used the following
`search terms: atrial fibrillation, atrial flutter, epidemiology, incidence,
`prevalence, mortality, and case fatality rate. MEDLINE, EMBASE,
`and LILACS were queried for studies published between 1980 and
`2010 (for LILACS, the time period was 1982–2010). There were no
`restrictions based on language of publication. Details of the search
`are outlined in Appendix II in the online-only Data Supplement.
`The initial search (phase 1) generated abstracts that were reviewed
`(phase 2) on the basis of prespecified inclusion and exclusion crite-
`ria (Appendix III in the online-only Data Supplement). Whereas all
`studies on AF epidemiology in the general population were included,
`studies conducted on selected clinical subgroups such as inpatients
`or those with heart failure were excluded to arrive at accurate esti-
`mates of AF burden at a population-wide level. The selected abstracts
`underwent full text reviews (phase 3) to confirm eligibility, generating
`
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`Figure 1. Conceptual disease model. Flow chart illustrating the conceptual disease model used (DisMod-MR software). The model
`includes the number of people without the disease (atrial fibrillation in this case), the number of people with the disease, the number
`of deaths associated with the disease, and the number of deaths resulting from all other causes. The transitions between these states
`are represented by incidence (i), remission (m), case fatality (f), and all other mortality (m). In the case of atrial fibrillation, remission was
`assumed to be zero. (Modified from Barendregt et al.24 Copyright © 2003 Barendregt et al; licensee BioMed Central Ltd.)
`
`

`

`Chugh et al
`
`Global Burden of Atrial Fibrillation
`
`839
`
`DisMod to estimate the total number of patients living with AF. The
`history of at least 1 confirmed AF episode is the common definition
`of AF used in prevalence studies. We used this definition in the mod-
`eling and estimation of different epidemiological parameters such as
`prevalence, incidence, and case fatality (excess mortality rate).21
`As for all conditions assessed in the GBD project, burden associ-
`ated with AF was measured as disability-adjusted life-years (DALYs).
`The DALY metric was introduced in the original GBD 1990 study as a
`means of assessing the disability of chronic disorders.22 DALYs com-
`bine information on premature death (years of life lost) and disability
`caused by the condition (years lived with disability). One DALY cor-
`responds to 1 lost year of health and is calculated as years of life lost
`plus years lived with disability. As previously described in detail,25,26
`years lived with disability are calculated by multiplying the estimated
`number of incident cases by the average duration of the disease and a
`disability weight factor (range, 0–1, where 0 is total health and 1 is total
`disability). Disability weights for sequelae of multiple disease condi-
`tions were estimated by 4 population-based surveys in Bangladesh,
`Indonesia, Peru, and Tanzania; a telephone survey in the United States;
`and an open-access Web-based survey.27 AF sequelae were defined as
`“daily medication and at least minimal interference with daily activi-
`ties” and accordingly assigned a disability weight of 0.031.
`
`Role of the Funding Source
`The funding sources had no influence over the study, the interpreta-
`tion of the results, writing of the manuscript, or decision to submit for
`publication. The corresponding author had full access to all the data
`in the study and had final responsibility for the decision to submit for
`publication.
`
`Results
`
`Data Availability
`The initial search generated 4574 abstracts (Appendix I in the
`online-only Data Supplement). Of these, 377 published stud-
`ies (8.2%) were identified as meeting initial criteria. After a
`full text review, 193 studies were excluded (ie, did not meet
`the prespecified quality measures), and the remaining184
`studies moved to the abstraction stage. The majority of studies
`were from Western Europe and North America (35.9% and
`35.6% of included data sources, respectively).
`
`Prevalence of AF
`Table 1 shows the estimated age-adjusted AF prevalence
`rates stratified by sex (Figure 2; complete data for all GBD
`regions are given in Table Ia and Ib in the online-only Data
`Supplement). In 1990, the estimated global prevalence rates
`
`(per 100 000 population) were 569.5 (95% UI, 532.8–612.7)
`in men and 359.9 (95% UI, 334.7–392.6) in women. In 2010,
`prevalence rates were 596.2 (95% UI, 558.4–636.7) in men
`and 373.1 (95% UI, 347.9–402.2) in women. The preva-
`lence rates showed a modest increase between 1990 and
`2010 (Figure 3) across both sexes. Developed countries had
`higher prevalence rates compared with developing countries;
`however, this difference was more pronounced in men than
`in women. For all time points, the prevalence was higher in
`men compared with women. There was significant varia-
`tion in prevalence between GBD regions. The lowest preva-
`lence rates (2010) were estimated in the Asia-Pacific region
`for both men and women (340.2 and 196.0, respectively).
`The highest rates were estimated in North America (925.7
`for men and 520.8 for women). The prevalence and inci-
`dence for Sub- Saharan Africa were lower compared with
`a developed region such as North America. Overall, for the
`Sub-Saharan Africa super-region, in 2010, the prevalence of
`AF (age-adjusted, per 100 000 population) was 659.8 (95%
`UI, 511.0–850.4) for men and 438.1 (95% UI, 340.2–561.0)
`for women. The median change in prevalence was higher in
`developed countries, with the largest increase noted in North
`America (40.1%) and the least change in Sub-Saharan Africa,
`East (3.4%; Table II in the online-only Data Supplement).
`Prevalence rates increased significantly with increasing age
`(Figures IA and IB in the online-only Data Supplement),
`with rates in the ≥35-year-old population observed to be
`more than double the overall prevalence. With the DisMod
`MR-estimated prevalence rates applied to the world popula-
`tion of 2010, the estimated number of individuals with AF
`globally is 20.9 million men (95% UI, 19.5–22.2 million)
`and 12.6 million women (95% UI, 12.0–13.7 million).
`
`Incidence of AF
`Table 2 shows the estimated age-adjusted incidence rates
`of AF stratified by sex (complete data for all GBD regions
`are given in Table IIIa and IIIb in the online-only Data
`Supplement). In 1990, the overall incidence rates of the world
`population were 60.7 (95% UI, 49.2–78.5) per 100 000 per-
`son-years in men and 43.8 (95% UI, 35.9–55.0) in women.
`In 2010, the estimated incidence rates were higher, 77.5
`(95% UI, 65.2–95.4) in men and 59.5 (95% UI, 49.9–74.9)
`
`Table 1. Estimated Age-Adjusted Prevalence Rates With 95% Uncertainty Intervals of Atrial Fibrillation (per 100 000 Population)
`for Men and Women
`
`1990
`
`1995
`
`2000
`
`2005
`
`2010
`
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`
`
`Men
` Global, all ages
` Age ≥35 y
` Developed countries
` Developing countries
`Women
` Global, all ages
` Age ≥35 y
` Developed countries
` Developing countries
`
`
`
`569.5 (532.8–612.7)
`1307.4 (1222.5–1407.3)
`608.2 (547·0–693.5)
`546.6 (503.0–599.6)
`
`578.1 (541.2–620.9)
`1327.3 (1243.2–1425.7)
`625.6 (564.0–712.5)
`551.1 (506.6–604.8)
`
`586.8 (549.8–629.5)
`1347.6 (1263.4–1445.8)
`643.1 (580.3–730.2)
`555.8 (511.0–610.1)
`
`595.1 (557.3–639.0)
`1366.6 (1281.0–1467.1)
`660.0 (594.5–740.8)
`561.3 (517.5–618.4)
`
`596.2 (558.4–636.7)
`1368.5 (1280.8–1462.7)
`660.9 (597.1–738.2)
`565.7 (522.9–617.6)
`
`359.9 (334.7–392.6)
`826.5 (768.4–902.3)
`362.5 (319.3–422.3)
`358.2 (329.8–393.0)
`
`363.4 (338.5–395.3)
`834.7 (776.6–909.2)
`370.1 (326.7–429.5)
`359.0 (330.8–394.0)
`
`366.7 (342.0–397.8)
`842.3 (784.7–915.5)
`377.5 (334.0–436.8)
`359·8 (331.5–395.0)
`
`369.6 (345.5–399.9)
`849.0 (792.4–919.6)
`385.1 (340.1–446.8)
`360.9 (331.6–396.0)
`
`373.1 (347.9–402.2)
`856.8 (797.7–923.5)
`387.7 (343.8–450.0)
`366.1 (337.4–400.8)
`
`

`

`840
`
` Circulation
`
` February 25, 2014
`
`Figure 2. World map showing the age-adjusted prevalence rates (per 100 000 population) of atrial fibrillation in the 21 Global Burden of
`Disease regions, 2010.
`
`in women, as shown in Figure 4. There were significantly
`higher (≈2-fold) incidence rates in developed regions com-
`pared with developing countries. For both time periods, sim-
`ilar to the observations for prevalence, AF incidence rates
`were higher in men compared with women. Again, there
`was great variation between GBD regions. The lowest inci-
`dence rates (2010) were estimated in the Asia-Pacific region
`for both men and women (33.8 and 19.8, respectively). The
`highest rates were estimated in North America (264.5 for
`men and 196.3 for women). As for prevalence, the incidence
`
`rates were also lower in the Sub-Saharan region, reported
`as 58.4 (95% UI, 43.7–78.5) and 42.7 (95% UI, 31.1–60.5)
`in men and women, respectively. Incidence rates were also
`higher in the older age groups (Figure IIA and IIB in the
`online-only Data Supplement).
`When the estimated incidence rates are applied to the
`world population of 2010, the estimated number of new
`AF cases per year is 2.7 million (95% UI, 2.3–3.3 mil-
`lion) for men and 2.0 million (95% UI, 1.7–2.6 million)
`for women.
`
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`Figure 3. Prevalence of atrial fibrillation: 1990 to 2010. Estimated age-adjusted global prevalence of atrial fibrillation (per 100 000
`population) for men and women from 1990 to 2010.
`
`

`

`Chugh et al
`
`Global Burden of Atrial Fibrillation
`
`841
`
`increases of 18.8% (95% UI, 15.8–19.3) and 18.9% (95% UI,
`15.8–23.5) for men and women, respectively (Table 4; com-
`plete data for all GBD regions are given in Table Va and Vb
`in the online-only Data Supplement; see Figure 8). In keeping
`with the higher incidence and prevalence of AF, DALYs were
`higher in developed compared with developing countries.
`The rate of change in DALYs was also higher in developed
`compared with developing countries (Table II in the online-
`only Data Supplement).
`
`Discussion
`Our systematic review of the current worldwide epidemio-
`logical data on AF confirms the emergence of this condition
`as a global epidemic with significant and progressive effects
`on estimated disability and mortality. Furthermore, there
`were specific differences identified on the basis of age and
`GBD region that are likely to have significant implications for
`global public health.
`As expected, higher rates of AF were observed in older age
`groups. For example, men 75 to 79 years of age have double
`the prevalence rate compared with men 65 to 69 years of age
`and >5-fold higher prevalence compared with men 55 to 59
`years of age. The 2010 rates are higher than the 1990 rates,
`with increases in both prevalence and incidence rates in both
`sexes. Other regional studies have reported an increasing prev-
`alence of AF, especially in the developed world. Piccini et al13
`reported a greater increase in the prevalence of AF (from 41.1
`to 85.8 per 1000 between 1993 and 2007, with an annual rate
`of increase of ≈5%) compared with the present study, which
`is likely to be related to differences in the population stud-
`ied, with the former study being restricted to elderly Medicare
`beneficiaries in the United States. The annual new cases of AF
`globally in 2010 were estimated at close to 5 million, which,
`together with the increasing trends observed, highlights the
`observation that the burden of AF is growing rapidly.
`The exact reasons for these trends are unknown but may be
`partly explained by aging trends in the global population. One
`hypothesis for the increasing incidence is that AF in the major-
`ity of people is a vascular disease caused by hypertension,
`atherosclerosis, and other cardiovascular risk factors, which
`increase arterial stiffness and cause diastolic dysfunction and
`atrial volume overload, resulting in AF. Analysis of global risk
`factors in the GBD 2010 study showed that high blood pressure
`is the number 1 risk factor globally (increasing from the fourth
`position in 1990), accounting for 7% of all global DALYs.
`High body mass index ranks sixth in the global list, ascending
`from the 10th position in 1990. Deaths attributable to hyperten-
`sion increased by 28.8% from 1990 to 2010, whereas deaths
`attributable to obesity increased by 71.7%.18 Thus, it appears
`that the increase in AF burden potentially could be linked to
`risk factors such as hypertension and obesity at a global level.
`Although these alterations can be observed as part of the aging
`process, they are also likely to be involved independently of
`aging. Although a renewed focus on risk factors may help,
`other contributors to increasing AF incidence such as aging of
`the population, better survival from other disease conditions,
`and improved diagnosis also need to be acknowledged.
`Temporal trends in AF prevalence may also result from lead
`time bias (such that AF cases may be diagnosed earlier in their
`
`Table 2. Estimated Age-Adjusted Incidence Rates with 95%
`Uncertainty Intervals of Atrial Fibrillation (per 100 000 Person-
`years) for Men and Women
`
`1990
`
`2010
`
`
`
`Men
` Global, all ages
` Age ≥35 y
` Developed countries
` Developing countries
`Women
` Global, all ages
` Age ≥35 y
` Developed countries
` Developing countries
`
`
`
`60.7 (49.2–78.5)
`141.0 (114.6–182.6)
`78.4 (67.5–91.9)
`50.0 (33.8–76.8)
`
`77.5 (65.2–95.4)
`181.2 (152.6–222.8)
`123.4 (107.6–141.5)
`53.8 (38.7–79.8)
`
`43.8 (35.9–55.0)
`102.0 (83.9–127.9)
`52.8 (45.0–62.9)
`36.0 (24.5–54.7)
`
`59.5 (49.9–74.9)
`139.7 (117.1–175.3)
`90.4 (77.8–104.5)
`40.0 (27.2–62.6)
`
`Mortality and Disease Burden Associated With AF
`The age-adjusted mortality rate (per 100 000 population)
`for AF in 1990 was 0.8 (95% UI, 0.5–1.1) for men and 0.9
`(95% UI, 0.7–1.2) for women. The age-adjusted mortality rate
`increased to 1.6 (95% UI, 1.0–2.4) and 1.7 (95% UI, 1.4–2.2)
`in 2010, representing 2-fold (95% UI, 2.0–2.2) and 1.9-fold
`(95% UI, 1.8–2.0) increases, for men and women, respectively
`(Table 3; full data for all GBD regions are provided in Table
`IVa and IVb in the online-only Data Supplement). Mortality
`increased steadily through 1995, 2000, and 2005 (Figure 5),
`especially in the developed world. Mortality associated with
`AF was higher in women overall; this was driven mainly by
`comparatively higher mortality in women (compared with
`men) in developing countries (Figure 6). In 2010, the esti-
`mated numbers of total deaths (men and women) represented
`<1% of the global mortality in the vast majority of the 21
`GBD regions (Figure 7).
`The estimated age-adjusted DALYs (per 100 000 popu-
`lation) resulting from AF were 54.3 (95% UI, 39.2–72.7)
`and 38.6 (95% UI, 28.9–50.5) in 1990 for men and women,
`respectively. This number increased to 64.5 (95% UI, 46.8–
`84.2) and 45.9 (95% UI, 35.7–58.5) in 2010, representing
`
`Downloaded from
`
`http://circ.ahajournals.org/
`
` by guest on July 10, 2018
`
`Figure 4. Incidence of atrial fibrillation: 1990 and 2010. Estimated
`age-adjusted global incidence (per 100 000 person-years) for
`men and women for 1990 and 2010.
`
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`

`842
`
` Circulation
`
` February 25, 2014
`
`Table 3. Estimated Age-Adjusted Mortality Rates With 95% Uncertainty Intervals (per 100 000 Population) Associated With Atrial
`Fibrillation for Men and Women
`
`1990
`
`1995
`
`2000
`
`2005
`
`2010
`
`
`
`Men
` Global, all ages
` Age ≥35 y
` Developed countries
` Developing countries
`Women
` Global, all ages
` Age ≥35 y
` Developed countries
` Developing countries
`
`
`
`0.8 (0.5–1.1)
`1.9 (1.3–2.8)
`1.3 (0.9–1.9)
`0.4 (0.2–0.8)
`
`0.9 (0.7–1.2)
`2.2 (1.8–3.0)
`1.1 (1.0–1.3)
`0.7 (0.4–1.4)
`
`0.9 (0.6–1.3)
`2.2 (1.4–3.1)
`1.6 (1.1–2.2)
`0.4 (0.2–0.8)
`
`1.1 (0.9–1.4)
`2.7 (2.2–3.4)
`1.4 (1.2–1.6)
`0.8 (0.4–1.4)
`
`1.1 (0.7–1.5)
`2.7 (1.7–3.6)
`2.0 (1.3–2.7)
`0.5 (0.3–0.9)
`
`1.4 (1.2–1.8)
`3.5 (2.8–4.4)
`1.9 (1.7–2.2)
`0.9 (0.5–1.5)
`
`1.3 (0.8–1.8)
`3.2 (2.0–4.4)
`2.3 (1.6–3.2)
`0.6 (0.3–1.1)
`
`1.7 (1.4–2.1)
`4.0 (3.4–5.0)
`2.3 (2.0–2.7)
`0.9 (0.6–1.6)
`
`1.6 (1.0–2.4)
`3.8 (2.4–5.8)
`2.7 (1.9–4.3)
`0.7 (0.4–1.3)
`
`1.7 (1.4–2.2)
`4.2 (3.4–5.4)
`2.4 (2.0–3.0)
`1.0 (0.6–1.7)
`
`course) and increased survival from coexistent cardiovascular
`conditions such as ischemic heart disease and heart failure.
`Improved management of these cardiovascular conditions
`may have resulted in a larger high-risk group. In addition,
`increased awareness of AF symptoms and clinical diagnosis
`likely play a role. Of interest, the change in AF prevalence
`from 2005 to 2010 was seen to be minimal, especially among
`men in the developed countries as opposed to developing
`countries. Although the exact reason for the leveling of preva-
`lence rates is difficult to ascertain, one possibility may be an
`improved awareness and focus on management of risk factors
`in the developed world.
`AF is known to have a significant impact on healthcare
`costs, with the major cost drivers being hospitalizations,
`stroke, and loss of productivity.6,28,29 In the present study, AF
`was associated with <1% of all deaths in most World Health
`Organization regions. However, AF is known to coexist and
`interact with other conditions, contributing to a worse prog-
`nosis than for individuals without AF. For example, recent
`meta-analyses have shown that patients with heart failure and
`myocardial infarction have worse outcomes if they also have
`AF.30,31 Moreover, new-onset AF in heart failure patients might
`be associated with a particularly poor prognosis.32,33
`
`There were significant variations in the AF burden by
`GBD region, with developed countries having a greater bur-
`den overall. Recent reports indicate that a higher degree of
`European ancestry is associated with an increased predispo-
`sition to AF.34 However, part of the global variation in AF
`epidemiology may also be attributable to better surveillance
`in developed countries. In the 1990 GBD study, no specific
`data for AF were reported, but cardiovascular diseases as a
`group accounted for 9.7% of the global DALYs, with isch-
`emic heart disease being the fifth ranking disorder in total
`number of DALYS (≈47×106), behind lower respiratory
`infections, diarrheal diseases, perinatal disorders, and uni-
`polar major depression.35 In 2010, ischemic heart disease
`moved up to the number 1 position, with cardiovascular
`disease accounting for 11.8% of global DALYs. With the
`exception of Sub-Saharan Africa and Oceania, cardiovas-
`cular disease ranked among the top 3 causes of DALYs in
`most regions.20 In keeping with these trends, DALYs related
`to AF increased by ≈18% from 1990 to 2010. Although the
`absolute DALYs related to AF (≈52 per 100 000 overall)
`are much lower compared with conditions such as chronic
`obstructive lung disease (1114 per 100 000), diabetes mel-
`litus (680 per 100 000), and chronic kidney disease (307
`
`Downloaded from
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`http://circ.ahajournals.org/
`
` by guest on July 10, 2018
`
`Figure 5. Mortality associated with atrial fibrillation:
`1990 to 2010. Estimated age-adjusted mortality
`(per 100 000 population) associated with atrial
`fibrillation from 1990 to 2010. UI indicates
`uncertainty interval.
`
`

`

`Chugh et al
`
`Global Burden of Atrial Fibrillation
`
`843
`
`Figure 6. Mortality associated with atrial fibrillation (AF) stratified by sex and type of region (developed vs