Articles

50 year trends in atrial brillation prevalence, incidence, risk

factors, and mortality in the Framingham Heart Study:
a cohort study
Renate B Schnabel, Xiaoyan Yin, Philimon Gona, Martin G Larson, Alexa S Beiser, David D McManus, Christopher Newton-Cheh, Steven A Lubitz,
Jared W Magnani, Patrick T Ellinor, Sudha Seshadri, Philip A Wolf, Ramachandran S Vasan, Emelia J Benjamin*, Daniel Levy*

Summary
Background Comprehensive long-term data on atrial brillation trends in men and women are scant. We aimed to
provide such data through analysis of the Framingham cohort over 50 years.
Methods We investigated trends in incidence, prevalence, and risk factors for atrial brillation and its association with
stroke and mortality after onset in 9511 participants enrolled in the Framingham Heart Study between 1958 and 2007.
We analysed trends within 10 year groups (195867, 196877, 197887, 198897, and 19982007), stratied by sex.

Published Online
May 8, 2015
http://dx.doi.org/10.1016/
S0140-6736(14)61774-8
See Online/Comment
http://dx.doi.org/10.1016/
S0140-6736(14)61991-7
*Contributed equally

Findings During 50 years of observation (202 417 person-years), 1544 cases of new-onset atrial brillation occurred
(of whom 723 [47%] were women). Between 195867 and 19982007, age-adjusted prevalence of atrial brillation
quadrupled from 204 to 962 cases per 1000 person-years in men and from 137 to 494 cases per 1000 person-years
in women; age-adjusted incidence increased from 37 to 134 new cases per 1000 person-years in men and from
25 to 86 new cases per 1000 person-years in women (ptrend<00001 for all comparisons). For atrial brillation
diagnosed by electrocardiograph (ECG) during routine Framingham examinations, age-adjusted prevalence per
1000 person-years increased (126 in 195867 to 257 in 19982007 in men, ptrend=00007; 81 to 118 in women,
ptrend=0009). However, age-adjusted incidence of atrial brillation by Framingham Heart Study ECGs did not change
signicantly with time. Although the prevalence of most risk factors changed over time, their associated hazards for
atrial brillation changed little. Multivariable-adjusted proportional hazards models revealed a 74% (95% CI 5086%)
decrease in stroke (hazards ratio [HR] 377, 95% CI 198720 in 19581967 compared with 19982007; ptrend=00001)
and a 25% (95% CI 346%) decrease in mortality (HR 134, 95% CI 097186 in 19581967 compared with
19982007; ptrend=0003) in 20 years following atrial brillation onset.
Interpretation Trends of increased incidence and prevalence of atrial brillation in the community were probably
partly due to enhanced surveillance. Measures are needed to enhance early detection of atrial brillation, through
increased awareness coupled with targeted screening programmes and risk factor-specic prevention.
Funding NIH, NHLBI, NINDS, Deutsche Forschungsgemeinschaft.

Introduction
With ageing populations, atrial brillation was
predicted to aect 612 million people in the USA by
2050 and 179 million in Europe by 2060.13 Atrial
brillation is a major public health problem with high
comorbidity,4 increased mortality risk,5 and soaring
health-care costs.6 The reasons for the increase in the
prevalence of atrial brillation is incompletely
understood7,8 but might be related to enhanced
detection, rising incidence, improved survival in
patients with cardiovascular conditions that predispose
to atrial brillation, and greater survival after onset of
atrial brillation.9 Many previous studies of trends
in atrial brillation were based on administrative or
hospital databases, which might be subject to
ascertainment biases. Evidence1,2,79 for an increase in
prevalence and reduced mortality after onset of atrial
brillation exists. Results of some administrative data1,8
suggest that the incidence of atrial brillation is
increasing, whereas results of other investigations10,11

show that the incidence and prevalence of atrial

brillation vary widely. Although trends in the
epidemiology of atrial brillation have been reported to
be similar in direction for both sexes, the exact
estimates have diered by sex, with higher prevalence
in men and variable incidence estimates in women.1,8
Increased awareness of atrial brillation and use of
routine electrocardiographs (ECG) and extended electrocardiographic monitoring devices enhance the detection
of atrial brillation, and thereby might identify more
cases in the community, thus increasing incidence and
prevalence because of enhanced surveillance.
Long-term trends for atrial brillation prevalence,
incidence, risk factors, and for stroke and mortality after
the onset of atrial brillation in community-based
cohorts have not been investigated systematically. With
routine assessment of atrial brillation and its risk
factors, as well as cardiovascular outcomes over the
course of 50 years, the Framingham Heart Study is
a unique resource to monitor long-term trends in

www.thelancet.com Published online May 8, 2015 http://dx.doi.org/10.1016/S0140-6736(14)61774-8

National Heart, Lung, and

Blood Institutes Framingham
Study, Framingham, MA, USA
(R B Schnabel MD, X Yin PhD,
P Gona Phd, M G Larson ScD,
A S Beiser PhD,
C Newton-Cheh MD,
S Seshadri MD, P A Wolf MD,
Prof R S Vasan MD,
Prof E J Benjamin MD,
Prof D Levy MD); Department of
Epidemiology
(Prof E J Benjamin) and
Department of Biostatistics
(X Yin, M G Larson, A S Beiser),
Boston University School of
Public Health, Boston, MA,
USA; Department of
Mathematics and Statistics,
Boston University, Boston, MA,
USA (M G Larson); Whitaker
Cardiovascular Institute,
(Prof R S Vasan,
Prof E J Benjamin), Evans
Memorial Medicine
Department (Prof R S Vasan,
Prof E J Benjamin), Cardiology
Section (J W Magnani MD,
Prof R S Vasan,
Prof E J Benjamin), Neurology
Department (A S Beiser,
S Seshardri, P A Wolf), and
Preventive Medicine Section
(P A Wolf, Prof R S Vasan,
Prof E J Benjamin, Prof D Levy),
School of Medicine, Boston
University, Boston, MA, USA;
Cardiology Division,
Department of Medicine
(D D McManus MD) and Division
of Biostatistics and Health
Services Research, Department
of Quantitative Health Sciences
(P Gona), University of
Massachusetts Medical School,
Boston, MA, USA; Population
Sciences Branch, Division of
Intramural Research, National
Heart, Lung, and Blood

Articles

Institute, National Institutes of

Health, Bethesda, MD, USA
(Prof D Levy); Cardiovascular
Research Center
(C Newton-Cheh, P T Ellinor MD),
Center for Human Genetic
Research (C Newton-Cheh) and
Cardiology Division
(C Newton-Cheh, S A Lubitz MD,
P T Ellinor MD), Massachusetts
General Hospital, Harvard
Medical School, Boston, MA,
USA; Program in Medical
Population Genetics, Broad
Institute of Harvard and
Massachusetts Institute of
Technology, Cambridge, MA,
USA (C Newton-Cheh,
P T Ellinor); and Deutsches
Zentrum fuer
Herz-Kreislauf-Forschung,
University Heart Center,
Department of General and
Interventional Cardiology,
Hamburg, Germany
(R B Schnabel)
Correspondence to:
Dr Renate B Schnabel,
Department of General and
Interventional Cardiology,
University Heart Center
Hamburg-Eppendorf,
20246 Hamburg, Germany
r.schnabel@uke.de

prevalence and incidence, risk factors, and outcomes of

atrial brillation in the community and might provide
insights to guide future prevention strategies.

Methods
Study design and participants
The Framingham Heart Study began in 1948 with
enrolment of the original cohort (5209 participants).12
The ospring cohort (5124 participants) was enrolled in
the early 1970s and comprised adult children of original
cohort participants and their spouses.13 Individuals who
were aged 5089 years at the beginning of follow-up were
eligible for analyses (4420 individuals from the original
cohort and 5091 from the ospring cohort). Due to small
numbers, we did not include atrial brillation cases that
occurred during the rst decade (194857) of study.
Baseline risk factors, follow-up times, and incidence data
were assigned to the decade of the index examination.
We dened the index examination as the last examination
prior to atrial brillation or censoring date but no more
than 10 years prior to onset or censoring. Individuals
contributed to time periods if they were free of atrial
brillation at the beginning of a time period and
contributed follow-up during that period. The date of last
follow-up was Dec 31, 2011.
All clinical characteristics were assessed from the index
examination, which was identied for each individual for
each time period. Study protocols were approved by the
Boston University Medical Center Institutional Review
Board. Participants provided written informed consent.

Procedures

See Online for appendix

During routine Framingham clinic visits (about every

2 years in the original cohort and every 48 years in the
ospring cohort), participants completed standardised
questionnaires, had physical examinations and 12-lead
ECGs. Regular health-status updates for cardiovascular
disease included requests for hospital admission or
outpatient records and ECGs. The diagnosis of atrial
brillation (or atrial utter) was made if at least
two Framingham Heart Study cardiologists veried the
rhythm abnormality on a collected ECG, including Holter
ECGs, telemetry, or other monitoring information;
whenever provided, the actual tracings were assessed. We
aimed to collect ECGs of atrial brillation done outside
the Framingham clinic visits for all participants for whom
there was a suspicion of heart rhythm disorder. Stroke
was diagnosed as a focal neurologic decit characterised
by a sudden onset and a duration of minimum of 24 h or
until death, if death occurred within 24 h of symptom
onset. Methods used to document, diagnose, ascertain,
and classify cardiovascular diseases in the Framingham
Heart Study have been published.14 We focused on risk
factors for atrial brillation that were consistently
reported, easily obtainable, and have been available over
the total period of the study. Detailed information on
ascertainment of other covariates is provided (appendix).

Statistical analysis
We examined time periods 195867, 196877, 197887,
198897, and 19982007. Atrial brillation prevalence
rates are person-years lived by individuals with atrial
brillation per 1000 total person-years lived during
each period. Age-adjusted period prevalence of atrial
brillation was calculated using the number of prevalent
atrial brillation cases divided by the person-time of
follow-up during each respective time period. We tested
for statistical signicance of trends over time periods by
Poisson regression.15 We used the SAS procedure PROC
GENMOD for trend testing.
Individuals who did not have atrial brillation at
the index examination were included in the analyses
for incidence. We calculated crude and age-adjusted
incidence rates for men and women separately. For each
sex, the incidence rate was calculated as the number of
new atrial brillation cases per 1000 person-years of
follow-up in each time period. The age distribution of
the overall sample was used to calculate standardised
incidence rates. For each combination of sex and time
period, the incidence rate was calculated by dividing the
number of atrial brillation events by the corresponding
exposure time. We directly standardised incidence
rates using the overall (pooled by sex and time) age
distribution, grouped into 10 year intervals, as the
constant reference age distribution. To account for
potential ascertainment bias over time, we repeated
calculations restricting atrial brillation cases to individuals diagnosed by ECGs during routine Framingham
clinic visits.
The risk factors for atrial brillation were retrieved
from the last routine clinic visit attended prior to atrial
brillation onset, if this visit took place no more than
10 years earlier. For individuals without atrial brillation,
risk factors were assessed from the last clinic visit
attended prior to the censoring date, also within 10 years
of the respective time period. The censoring date was
either end of a decade, or last contact date or death date,
whichever came rst. The following risk factors were
considered: age, smoking status, alcohol consumption,
body-mass index (BMI), systolic blood pressure,
hypertension treatment, diabetes, electrocardiographic
left ventricular hypertrophy, clinically signicant heart
murmur with at least 3/6 systolic or any diastolic
murmur, diagnosed heart failure, and myocardial
infarction. For each risk factor we did a trend test to
determine whether its prevalence increased or decreased
over time, adjusting for age and sex using logistic
regression models.
Proportional hazards models were applied (separately
for each time period and pooled by sex) to assess the
association of each clinical risk factor with the
development of atrial brillation after the proportionality
assumption was tested and conrmed. We tested for
linear trend over time periods in the log-hazards of risk
factors for incident atrial brillation by including an

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Articles

interaction term between risk factor and period in the

proportional hazard model. If the interaction term was
signicant (p<005), we concluded there was a trend in
the log-hazard across decades.
We calculated population-attributable risk for each
risk factor with the Rockhill approach modied for
adjusted hazards ratios (appendix). Inputs were
age-adjusted and sex-adjusted risk factor prevalence in
cases and age-adjusted and sex-adjusted risk factor
hazards ratios for atrial brillation incidence by time
period. Each input was either constant or allowed to
change over time according to its statistical signicance
from trend tests mentioned previously.
Age-adjusted and sex-adjusted and multivariableadjusted proportional hazards analyses were used to
calculate hazards ratios for mortality after atrial brillation
195867

onset according to time period for the total sample. We

stratied models by sex and adjusted survival curves for
age at atrial brillation diagnosis.16 In secondary analyses,
we calculated adjusted hazards ratios for stroke in
20 years after atrial brillation onset. We used SAS
version 9.2 for analyses. A two-tailed p value of less than
005 was regarded as signicant.

Role of the funding source

The funder had no role in the design and conduct of
the study, the collection, management, analysis, and
interpretation of the data, the preparation, review, or
approval of the manuscript, or the decision to submit the
manuscript for publication. EJB, RBS, and DL had full
access to all the data in the study and had nal
responsibility for the decision to submit for publication.

196877

197887

198897

19982007

ptrend*

Men
Number at risk
Person-years at risk
Age, years

1925

2399

2569

2595

2128

14 044

17 448

19 223

19 196

17 270

550 (58)

586 (81)

604 (99)

608 (106)

631 (105)

Atrial brillation based on all sources

Number of atrial brillation cases
Crude incidence rate
Age-adjusted incidence rate
Age-adjusted period prevalence

40
285
370

101
579
731

166
864
907

266
1386

248
1436

<00001

1432

1337

<00001

204

377

523

818

962

<00001

23

38

56

70

81

Atrial brillation based on Framingham Heart Study

Clinic ECGs
Number of atrial brillation cases
Crude incidence rate
Age-adjusted incidence rate
Age-adjusted period prevalence

161
183
126

212
255
191

281
286
240

343
335
257

430
375
257

<00001
006
00007

Women
Number at risk
Person-years at risk
Age, years

2401

2924

3174

3315

2857

18 356

23 360

25 254

25 046

23 220

550 (58)

596 (84)

35

90

627 (107)

629 (118)

647 (119)

Atrial brillation based on all sources

Number of atrial brillation cases
Crude incidence rate
Age-adjusted incidence rate
Age-adjusted period prevalence

191
252

385
469

161
638
547

194
775
614

243
1047
855

137

251

295

343

494

21

46

51

50

52

<00001
<00001
<00001

Atrial brillation based on Framingham Heart Study

clinic ECGs
Number of atrial brillation cases
Crude incidence rate

110

Age-adjusted incidence rate

131

Age-adjusted period prevalence

81

188
211
148

193
164
139

191
140
126

213
158
118

003
013
0009

Data are n or mean (SD). All participants were 5089 years of age and free of atrial brillation at enrolment. Atrial brillation incidence rates are per 1000 person-years of
follow up. Adjusted incidence rates were calculated using direct standardisation of sex-pooled and time-pooled 10-year age groups. Atrial brillation prevalence rates are
person-years lived by atrial brillation individuals per 1000 total person-years lived during each period, ie, by all person-years contributed by survivors (including those
developed atrial brillation before the period) at the beginning of the period. Atrial brillation cases include all those participants who developed atrial brillation in or before
the corresponding period. For the rst period, during which there was no participant in the 8089 year age group, the incidence rates were standardised to the overall
distribution among the remaining age groups only. *ptrend was obtained with Poisson regression. Mean age is for the population at risk for development of atrial brillation;
age is the earliest eligible age within a decade.

Table 1: Atrial brillation incidence rates and age-adjusted period prevalence, by sex and decade

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Articles

Results
The 50 year observation period extended from 1958 to
2007 and comprised 202 417 person-years of follow-up,
during which 1544 individuals (821 men, 723 women)
had new-onset atrial brillation, ascertained from
routine Framingham clinic visits and outside medical
records. Examination of atrial brillation ascertained
from all sources indicated about a quadruple increase
in age-adjusted period prevalence from 195867 to
19982007 (table 1). Similarly, the age-adjusted incidence
of atrial brillation from all sources increased progressively over time. A visual summary of trends in
incidence and prevalence of atrial brillation and the
sources of rst diagnosis are provided in the appendix.
When analysed by the mode of rst detection of atrial
brillation, a rst diagnosis on Framingham clinic
ECGs decreased, whereas rst detection on outside
medical records strikingly increased over the decades
(appendix).
Increases in period prevalence over time were less
pronounced but remained signicant when analyses
were restricted to atrial brillation detected by ECG at a
Framingham Study clinic visit (table 1). By contrast,
age-adjusted incidence of atrial brillation by time period

also increased numerically but did not reach signicance

in cases detected by ECG at a routine Framingham clinic
visit (table 1).
Table 2 shows age-adjusted prevalence of risk factors
at time of atrial brillation onset. 179 individuals who
had no eligible index clinic visits were excluded from
this analysis. The admixture of underlying risk factors
changed substantially with time. The prevalence of
smoking and heavy alcohol consumption decreased
over time, whereas prevalence of obesity and diabetes
increased. The distribution of hypertension categories
preceding atrial brillation cases shifted downward
(less hypertensive), whereas rates of hypertension
treatment increased. Prevalence of electrocardiographic
left ventricular hypertrophy, clinically signicant heart
murmur, and heart failure declined over time, whereas
the proportion of atrial brillation cases with previous
myocardial infarction remained fairly constant.
Sex-specic results for risk factor prevalence at the start
of each time period for participants with atrial
brillation are provided in the appendix. Women with
atrial brillation were older and tended to have a more
benecial risk factor prole than did men, except for
higher blood pressure, despite a higher proportion of

195867

196877

197887

198897

19982007

Number of new-onset atrial brillation cases

70

178

284

399

434

Smoking

27 (409%)

35 (223%)

60 (217%)

62 (156%)

55 (127%)

ptrend*

Trend direction

00002

Decrease

Alcohol consumption
None

25 (424%)

53 (317%)

127 (467%)

168 (427%)

186 (440%)

064

No trend

Mild

28 (475%)

92 (551%)

122 (449%)

200 (509%)

214 (506%)

028

No trend

6 (102%)

22 (132%)

23 (85%)

25 (64%)

23 (54%)

0005

Decrease
Decrease

Moderate or heavy
Body-mass index
Normal (<25 kg/m)

20 (303%)

56 (357%)

107 (399%)

115 (304%)

105 (277%)

00009

Overweight (2530 kg/m)

28 (424%)

68 (433%)

101 (377%)

173 (458%)

140 (369%)

042

Obese (31 kg/m)

18 (273%)

33 (210%)

60 (224%)

90 (238%)

134 (354%)

<00001

Optimal (<120 mm Hg)

5 (71%)

19 (107%)

36 (127%)

53 (133%)

88 (203%)

<00001

Increase

Normal (120129 mm Hg)

9 (129%)

13 (73%)

32 (113%)

57 (143%)

73 (169%)

0001

Increase
Increase

No trend
Increase

Systolic blood pressure

High-normal (130139 mm Hg)

8 (114%)

23 (129%)

51 (180%)

75 (188%)

91 (210%)

0009

Stage I hypertension (140159 mm Hg)

21 (300%)

64 (360%)

99 (350%)

134 (336%)

108 (249%)

0001

Decrease

Stage IIIV hypertension (160 mm Hg)

27 (386%)

59 (331%)

65 (230%)

80 (201%)

73 (169%)

<00001

Decrease

Hypertension treatment

15 (221%)

55 (329%)

135 (477%)

219 (554%)

257 (598%)

<00001

Increase

Diabetes

4 (57%)

25 (140%)

44 (157%)

66 (167%)

80 (196%)

0004

Increase

Electrocardiographic left ventricular hypertrophy

9 (129%)

21 (118%)

19 (69%)

23 (62%)

12 (29%)

<00001

Decrease

14 (200%)

32 (189%)

52 (192%)

42 (107%)

31 (81%)

<00001

Decrease

Prevalent heart failure

4 (57%)

15 (84%)

17 (60%)

23 (58%)

15 (35%)

0009

Decrease

Prevalent myocardial infarction

6 (86%)

16 (90%)

27 (95%)

45 (113%)

47 (108%)

027

No trend

Signicant heart murmur

Data are n (%). In total 1365 (884%) atrial brillation cases were identied with index examinations. The remaining 179 patients were excluded from this analysis for
missing eligible index examinations. This table presents the age-adjusted and sex-adjusted prevalence of baseline characteristics for atrial brillation cases with index
examination. For each characteristic, prevalence in dierent decades are predicted values from a logistic model where the characteristic is the outcome variable, decade as
main predictor if the trend test is signicant, with age and sex as covariates. The observed prevalence by sex is presented in the appendix. The prevalence might not add up
to exactly 1 for multiple categorical variables because of rounding. *p values are obtained from logistic models adjusting for age and sex tted on observed data. trend was
not statistically significant.

Table 2: Baseline characteristics in individuals with new-onset atrial brillation, by decade

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Articles

Number of individuals
Male sex

195867

196877

197887

198897

19982007

4292

5119

5151

5235

4295

160 (100257)

184 (136247)

167 (132211)

210 (171257)

149 (123180)

ptrend*

076

Age (years)
5059

100

100

100

100

100

6069

348 (196619)

938 (549160)

389 (257589)

242 (167350)

498 (349710)

056

7079

300 (142636)

1230 (720210)

453 (300685)

605 (434843)

735 (528102)

027

8089

739 (480114)

783 (549112)

933 (668130)

059

096 (057162)

074 (050110)

100 (074134)

101 (077134)

099 (074132)

018

Smoking
Alcohol consumption
None

100

100

100

100

100

Mild

082 (047144)

104 (073148)

085 (066111)

121 (098150)

107 (088131)

007

Moderate or heavy

082 (033204)

220 (131372)

086 (055135)

131 (085203)

110 (071169)

091

Normal (<25 kg/m)

100

100

100

100

100

Overweight (2530 kg/m)

143 (081256)

117 (082167)

102 (077134)

127 (100162)

113 (087146)

092

Obese (31 kg/m)

263 (139499)

204 (132315)

147 (107203)

133 (101176)

137 (105178)

019

Body-mass index

Systolic blood pressure

Optimal (<120 mm Hg)

100

100

100

100

100

Normal (120129 mm Hg)

176 (059525)

053 (026107)

075 (046121)

111 (076161)

094 (069129)

071

High-normal (130139 mm Hg)

129 (042395)

079 (043145)

097 (063149)

127 (089181)

119 (089160)

053

Stage I hypertension (140159 mm Hg)

195 (073521)

139 (083234)

116 (079172)

147 (106203)

089 (067119)

001*

Stage IIIV hypertension (160 mm Hg)

263 (100693)

136 (079232)

121 (079185)

128 (089183)

115 (084158)

002*

Hypertension treatment

171 (096306)

163 (118227)

135 (106171)

168 (137206)

132 (108160)

031

Diabetes

106 (038290)

142 (093217)

159 (115220)

149 (115195)

125 (098160)

058

Electrocardiographic left ventricular hypertrophy

312 (154633)

241 (152381)

195 (122313)

249 (163382)

25 (121383)

040

Signicant heart murmur

619 (343112)

284 (192-420)

331 (241454)

192 (139267)

158 (109229)

00003

Heart failure

262 (095725)

315 (184541)

233 (142382)

236 (154362)

143 (085240)

001

Myocardial infarction

245 (104579)

170 (101286)

166 (111249)

158 (116216)

146 (107198)

019

Data are hazard ratio (95% CI). indicates insucient data to estimate prevalence. Characteristics were assessed at index examinations. For atrial brillation cases, the index examination was the last examination
attended prior to atrial brillation diagnosis but no more than 10 years earlier; for individuals without atrial brillation, it was the last examination prior to censoring date also within 10 years, where censoring
date was either end of a decade, or last contact date or death date whichever came rst. Hazard ratios are expressed for the condition present in dichotomous variables. *p value for trend was obtained by testing
whether the regression coecient of interaction term of risk factor and period in Cox model equals 0. For trend, time periods were coded 1 (195867), 2 (196877), 3 (197887), 4 (198997) and 5 (19982007).
Categories for alcohol consumption were mild alcohol consumption: 17 units per week in women, 114 units per week in men; moderate or heavy alcohol consumption: more than 7 units per week in women,
more than 14 units per week in men. Decreasing hazard ratios over decades. For details of the statistics see appendix.

Table 3: Trends in age-adjusted and sex-adjusted hazards ratios for risk factors of incident atrial brillation, by decade of onset of atrial brillation

hypertension treatment. Trends in prevalence of risk

factors were very similar in both sexes, except for
smoking, which declined in men, but not in women.
Table 3 shows age-adjusted and sex-adjusted hazards
ratios for clinical risk factors in relation to atrial
brillation incidence, by time period. Hazards ratios of
most risk factors in relation to their association with
atrial brillation remained similar across the time
periods; age was the greatest risk factor for development
of atrial brillation. The unstable estimates in the rst
decades of the study are due to the low number of atrial
brillation cases in the earliest time periods. We
observed a decrease in hazards for hypertension,
clinically signicant heart murmur, and heart failure
with time.
Because of fairly stable hazards ratios over time,
trends in population-attributable risk largely indicated
changes in prevalence of risk factors (table 4). We

observed increases over time in population-attributable

risks for higher BMI and diabetes. We noted a decrease
in attributable risk for higher blood pressure, whereas
a substantial increase in population-attributable risk
for hypertension treatment was seen in addition to
decreases in electrocardiographic left ventricular
hypertrophy, valvular heart disease, and heart failure.
Among modiable risk factors for atrial brillation,
BMI, blood pressure, and anti-hypertensive treatment
carried the greatest population-attributable risks in the
most recent data, 19982007.
Improvements over time in age-adjusted survival
following the onset of atrial brillation were observed in
men and women (p<00001 for both sexes; gure). Risk
factor-adjusted hazards ratios for mortality are shown in
the appendix. We observed a 254% (95% 31461)
decrease in multivariable-adjusted mortality following
onset of atrial brillation between 195867 (hazard ratio

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Articles

195867

196877

197887

198897

19982007

Current smoking

Not contributing

Not contributing

Not contributing

Not contributing

Not contributing

Trend

Alcohol consumption

Not contributing

Not contributing

Not contributing

Not contributing

Not contributing

Body-mass index

120

129

141

154

169

Increase

Systolic blood pressure

473

330

199

83

21

Decrease

Hypertension treatment

98

120

145

170

195

Increase

Diabetes

32

37

44

51

59

Increase

Electrocardiographic left
ventricular hypertrophy

104

69

45

29

18

Decrease

Signicant heart murmur

219

154

101

61

31

Decrease

Heart failure

78

56

39

25

14

Decrease

Myocardial infarction

36

36

36

36

36

No change

For risk factors without trend in prevalence, the average predicted prevalence from logistic models with age and sex as predictors (table 2) were used in population-attributable
risk calculation; for factors with trend in prevalence, the average predicted prevalence from logistic models with age, sex and period as predictors were used in population
attributable risk. Risk factors with non-signicant hazards ratios (p value >005) were deemed not contributing (appendix). For risk factors without trend in hazards ratio, the
constant hazards ratio estimated from Cox models with age, sex, period and risk factors as predictors (appendix) were used in population attributable risk calculation; for
factors with trend in hazards ratio, the hazards ratios from Cox models with age, sex, period, risk factors, and period and risk factor interaction as predictors (appendix) were
used in population attributable risk calculation.

Table 4: Population-attributable risks of incident atrial brillation risk factors, by decade of onset of atrial brillation

Men

Women
19982007
198897
197887
196877
195867

10

Age-adjusted survival

08

06

04

02

0
0
Number at risk
195867 38
196877 99
197887 146
198897 235
19982007 223

10

15

Time from atrial fibrillation diagnosis (years)

17
56
75
141
112

11
33
44
81
23

10

15

Time from atrial fibrillation diagnosis (years)

8
23
27
40
..

32
79
138
164
211

22
42
59
89
115

16
22
31
45
29

11
9
19
18
..

Figure: Age-adjusted survival after new onset of atrial brillation, by sex and decade, in men and women

[HR] 134, 95% CI 097186) and 19982007 (referent

HR 10; ptrend=0003). Trends were similar in sexstratied analyses. Age-adjusted survival rates for 5 year
intervals by decade of atrial brillation onset increased
in both sexes over the observational time periods
(appendix).
Multivariable-adjusted hazard ratios for stroke in
20 years after onset of atrial brillation showed a 74%
reduction in risk of stroke between 195867 (HR 377,
95% CI 198720) and 19982007 (referent HR 10;
ptrend=00001; appendix p 19). Trends were similar in sexstratied analyses, but did not reach statistical
signicance in men.
6

Discussion
Over the course of 50 years of observation of a
community-based sample, we observed an increasing
prevalence and incidence of atrial brillation
accompanied by improved survival and reduced risk of
stroke after onset of atrial brillation (panel). When we
restricted our analyses to atrial brillation cases detected
by ECG at routine Framingham Heart Study clinic visits
(ie, uniform ascertainment), the increase in prevalence
of atrial brillation persisted, but the trend in
age-adjusted incidence was far less pronounced and did
not reach signicance. Whereas the prevalence of risk
factors for atrial brillation has changed over time, their

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Articles

hazards ratios for atrial brillation changed only slightly.

We analysed population-attributable risk over time and
noted increases in the attributable risk for atrial
brillation owing to higher BMI and diabetes. We noted
signicant declines in the attributable risks due to
electrocardiographic left ventricular hypertrophy,
clinically signicant heart murmurs, and heart failure.
Trends were similar in both sexes. In addition, we noted
a decrease of about 254% (95% CI 31461%) in
fatality after onset of atrial brillation between 195867
and 19982007. In secondary analyses, we also saw a
decrease in the risk of stroke.
Previous investigations have shown an increase in the
prevalence of atrial brillation in industrialised countries
from the 1970s to the turn of the 21st century,3,7,8 and our
data suggest that this trend is continuing. In parallel,
hospital admissions and health-care services for atrial
brillation have risen,9 potentially as a result of better
awareness of atrial brillation as a life-threatening
disorder. In addition, prevalence might have increased
with a decreasing number of fatalities due to atrial
brillation,9 improved therapies for cardiovascular
disease (eg, myocardial infarction and heart failure),17 and
better use of anticoagulation18 in patients with atrial
brillation. Despite the low number of individuals with
atrial brillation and secondary stroke in our sample, we
showed a decline over time in strokes occurring in
individuals diagnosed with atrial brillation. Our ndings
are in line with data19 that show a decline in stroke rates,
including thromboembolic strokes, during the past few
decades. These results might indicate that specic
treatment of atrial brillation patients have reduced
adverse outcomes, including stroke and mortality.
The dual ndings of rising prevalence and longer
survival after onset of atrial brillation might be
attributable, in part, to early detection of the disease due
to improvements in surveillance methods (ie, lead-time
bias due to more frequent electrocardiographic
monitoring). To account for this potential ascertainment
bias, we repeated analyses using only the ECGs from
routine periodic Framingham Heart Study clinic visits.
Routinely registered ECGs conrmed the increase
in prevalence of atrial brillation; however, the trend in
incidence rates was no longer signicant. Trends
in atrial brillation frequency in men were paralleled in
women with lower absolute numbers. Similar sex
dierences have been reported1,2 in projections of atrial
brillation disease distribution. By contrast with
Icelandic data,8 our cohort data of atrial brillation
incidence shows an increase in trend in both men and
women. Of note, mortality rates in women with
manifest atrial brillation were almost as high as in
men, consistent with previous publications.20
We conrmed a sharp incidence of atrial brillation
with each decade of advancing age older than 60 years.
We found notable trends in prevalence of several atrial
brillation risk factors over time in both sexes. By

Panel: Research in context

Systematic review
In the past decade, atrial brillation has been recognised as a disease of increasing
importance in ageing populations worldwide.13 Related morbidity and health-care costs
are substantial.46 However, the causes of the increase in atrial brillation prevalence is
unclear. High prevalence might relate to increased incidence and reduced case fatality.
Recognition of atrial brillation as a relevant cardiac disease might have contributed to
increased awareness of the problem. Detection of an often intermittent disease is central
for the diagnosis, and the number of identied cases in the community might have risen
because of improvements in screening. Furthermore, survival after atrial brillation
manifestation might have improved.9 Most previous reports on trends in atrial brillation
were based on administrative or hospital databases, which are subject to ascertainment
biases,1,79 leading to a wide variation in incidence and prevalence estimates.10,11 Whereas
the growing burden of atrial brillation has been identied in many studies, true
long-term trends in atrial brillation incidence and mortality in a community-based cohort
have not been investigated systematically. To identify preventive measures, a critical rst
step is to understand risk-factor associations and their population-attributable risk. The
population-attributable risk of known risk indicators for atrial brillation and the change
in that risk over decades have not been investigated in depth. The community-based
Framingham Heart Study provides a unique setting with continuous risk factor and atrial
brillation ascertainment from more than ve decades of data collection.
Interpretation
Our data reveal several important ndings. The probable contribution of improved
awareness of atrial brillation to changing trends in incidence and prevalence is
suggested by a comparison of results from all newly diagnosed atrial brillation cases
versus those detected using routine ascertainment based on the Framingham clinic visit
electrocardiogram only. The prevalence of most modiable risk factors has changed over
time, but the associated hazards for atrial brillation have remained fairly constant. Atrial
brillation incidence rates are not declining, and survival of patients with atrial brillation
is longer. Improved outcomes after atrial brillation onset might arise from successful,
yet often complex and costly treatment of atrial brillation and from earlier detection
(lead time) due to heightened awareness and improved surveillance. Many cases of atrial
brillation still have complications, such as stroke and heart failure. On the basis of the
results of this study, we speculate that earlier detection and successful prevention of atrial
brillation sequelae might reduce mortality. The growing burden of atrial brillation
merits consideration of public health approaches to enhance early detection through
increased awareness, targeted screening programmes, and risk-factor-specic prevention.

contrast, the strength of association of risk factors with

incidence of atrial brillation changed only slightly over
time. Sex dierences in classical atrial brillation risk
factors known from prior reports persisted throughout
the study period.21 Early diagnosis and eective treatments
for valvular heart disease and heart failure22,23 might have
contributed to a decrease in the risk of developing atrial
brillation and a decline in attributable risk.
Hypertension and its treatment were the two greatest
attributable risks of all modiable risk factors. In the
decades of follow-up, mean systolic blood pressure levels
and prevalence of electrocardiographic left ventricular
hypertrophy, an indicator of hypertensive target-organ
damage, probably declined because of a concurrent
doubling in treatment of hypertension.24 Such trends
might be a result of improved awareness, treatment, and
control of hypertension.25,26 Results of clinical trials27

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Articles

suggest a decline in atrial brillation incidence with blood

pressure control and regression of electrocardiographic
left ventricular hypertrophy. But atrial brillation was not
systematically collected as a primary endpoint in previous
hypertension treatment trials, and more randomised trial
data are necessary to identify the consequences and
optimal levels of blood pressure lowering on atrial
brillation prevention. The continuing trend of rising
BMI and diabetes, which contributed to the increases in
population-attributable risks for atrial brillation, might
be a harbinger of future trends. The extent to which
changes in population-attributable risk might explain
reported trends in atrial brillation prevalence needs to
be investigated in large datasets.
The number of atrial brillation cases in the rst
decades of reporting was small and might provide
unstable estimates. For low-frequency conditions, the
standard errors of the hazards ratios were large, and we
had restricted power to detect trends across decades of
the study period. Dierent inter-examination intervals
for original cohort and ospring cohort participants
might relate to the number of atrial brillation cases
seen in Framingham clinic ECGs and thus might have
biased estimates of disease distribution. We did not
distinguish between atrial brillation and atrial utter or
between atrial brillation patterns (eg, paroxysmal vs
persistent), so we cannot comment on temporal trends
in these atrial brillation subsets. We acknowledge that
our ascertainment of atrial brillation might be biased
towards long-lasting atrial brillation and the most
severely aected individuals; indeed, awareness of
clinically unrecognised atrial brillation is increasing.28
Since the Framingham sample used for this analysis
is of European descent, our results might not be
representative for other races or ethnicities. Whereas
previous investigations assessing trends in prevalence
and incidence of atrial brillation were mainly referralbased or used administrative databases, the Framingham
Heart Study provides a unique setting with continuous
data collection and outcome ascertainment in a
community-based sample.
Assessment of variation in the risk factors associated
with atrial brillation is an important step in
understanding the changes in prevalence of atrial
brillation over time. Increased BMI, for example, is the
largest of all modiable risk factors for atrial brillation,
which suggests a potential preventive treatment strategy
through weight loss. Public eorts have been successful
in reducing the risk factor burden for cardiovascular
disease.29 Reduced incidence of coronary heart disease,
improved control of risk factors, and evidence-based
therapies seem to have eectively lowered the rate of
hospital admissions for heart failure.30 Although increased
survival after onset of atrial brillation onset might
indicate therapeutic successes for atrial brillation and its
underlying risk factors, the increase in prevalence of atrial
brillation is indicative of a mounting future burden.
8

In view of the increasing prevalence of atrial brillation,

our study suggests three major goals in clinical and
public health: awareness of atrial brillation as a serious
disease needs to be further enhanced, ecient screening
needs to be implemented, and modiable risk factors,
primarily hypertension and BMI, should be explored as
potential preventive targets.
Our data show that increases in prevalence of atrial
brillation in both sexes from a large community-based
cohort might be explained by increased survival following
atrial brillation onset. By contrast, increasing incidence
rates seem to be due, in part, to changes in awareness,
ascertainment, and coding practices in the past 50 years.
The signicant trend in increasing prevalence underscores the need for additional research of better screening
and interventions to prevent atrial brillation and its
adverse consequences.
Contributors
EJB and DL had full access to all of the data in the study and take
responsibility for the integrity of the data and the accuracy of the data
analysis. RBS, XY, PG, MGL, EJB, and DL designed the study. RBS,
CN-C, PAW, SAL, SS, EJB, and DL acquired the data. RBS, XY, PG,
MGL, ASB, DDM, SAL, JWM, RSV, EJB, and DL analysed and
interpreted the data. XY, MGL, DDM, CN-C, SAL, JWM, PTE, SS, PAW,
and EJB critically revised the manuscript for important intellectual
content. XY, PG, MGL, and ASB performed the statistical analyses of the
data. EJB and DL obtained the funding. RBS wrote the rst draft and
submitted the nal version of the report. All authors have seen the nal
submitted article and agree with its contents.
Declaration of interests
We declare no competing interests.
Acknowledgments
EJB was supported by NIH/NHLBI contract N01-HC-25195 and NIH
grants 1RC1HL101056, HL102214, and AG028321. EJB and PTE were
supported by NIH grant 2R01HL092577. PTE was supported by
Fondation Leducq (14CVD01) and NIH grants 1R01HL092577,
1RC1HL101056, 1R01HL102214, 1R01AG028321, R01HL104156, and
1K24HL105780 and received the American Heart Association
Established Investigator Award 13EIA14220013. RSV was supported by
NIH grants HL080124, HL077477, HL71039, and HL093328. PAW, SS,
and ASB were supported by NIH grant 6RO1-NS-17950. RBS was
supported by the Deutsche Forschungsgemeinschaft (German
Research Foundation) Emmy Noether Program SCHN 1149/3-2. CNC
was supported by the NIH grant HL080025 and received the Doris
Duke Charitable Foundation Clinical Scientist Development Award
and the Burroughs Wellcome Fund Career Award for Medical
Scientists. SAL was supported by the NIH/NHLBI grant
1K23HL114724. DDM received additional partial salary support by NIH
grants 1U01HL105268-01 and KL2RR031981.
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