Cardiac Arrhythmias and Sleep

Cardiac Arrhythmias in Obstructive Sleep Apnea (from the
Akershus Sleep Apnea Project)
Silje K. Namtvedt, MDa,c, Anna Randby, MDa,c, Gunnar Einvik, MDa,c,
Harald Hrubos-Strøm, MDb,c, Virend K. Somers, MD, PhDd, Helge Røsjø, MDa,c, and
Torbjørn Omland, MD, PhD, MPHa,c,*
Increased prevalence of cardiac arrhythmias has been reported in patients with severe
obstructive sleep apnea (OSA), but this may not be generalizable to patients from the
general population with a milder form of the condition. The aim of this study was to assess
the association between cardiac arrhythmias and OSA of mainly mild and moderate
severity. In total, 486 subjects (mean age 49 years, 55% men) recruited from a populationbased study in Norway underwent polysomnography for OSA assessment and Holter
recordings for arrhythmia assessment. Of these, 271 patients were diagnosed with OSA
(apnea– hypopnea index [AHI] >5, median AHI 16.8, quartiles 1 to 3 8.9 to 32.6). Mean
nadir oxygen saturations were 82% and 89% in patients with and without OSA, respectively. Ventricular premature complexes (>5/hour) were more prevalent in subjects with
OSA compared to subjects without OSA (median AHI 1.4, quartiles 1 to 3 0.5 to 3.0) during
the night (12.2% vs 4.7%, p ⴝ 0.005) and day (14% vs 5.1%, p ⴝ 0.002). In multivariate
analysis after adjusting for relevant confounders, AHI was independently associated with
an increased prevalence of ventricular premature complexes at night (odds ratio per 1-U
increase of log-transformed AHI 1.5, 95% confidence interval 1.1 to 2.0, p ⴝ 0.008) and
during the day (odds ratio 1.37, 95% confidence interval 1.0 to 1.8, p ⴝ 0.035). In
conclusion, the prevalence of ventricular premature complexes is increased in middle-aged
patients with mainly mild or moderate OSA, suggesting an association between OSA and
ventricular arrhythmias even in mild OSA. © 2011 Elsevier Inc. All rights reserved. (Am
J Cardiol 2011;108:1141–1146)
The association between obstructive sleep apnea (OSA)
and cardiac arrhythmias is supported by observations from
several sleep clinic-based studies, in which up to 60% of
patients with severe OSA were found to develop cardiac
arrhythmias.1–3 Furthermore, the Outcomes of Sleep Disorders in Older Men Study4 and the Sleep Heart Health Study5
have recently complemented these results by showing that
elderly subjects and subjects with severe OSA from the
general population also have a high prevalence of cardiac
arrhythmias. However, there is limited information on the
prevalence of cardiac arrhythmias during the night and day
in community-dwelling middle-aged subjects with predominantly mild and moderate unrecognized OSA. Accordingly,
we aimed to assess the prevalence of arrhythmias in this
population and assess the association between arrhythmias
and indexes of OSA severity, i.e., apnea– hypopnea index
(AHI) and nadir oxygen saturation (SaO2).

a

Division of Medicine and bDepartment of Otorhinolaryngology, Akershus University Hospital, Lørenskog, Norway; cUniversity of Oslo, Oslo,
Norway; dCardiovascular Diseases, Department of Internal Medicine,
Mayo Clinic and Foundation, Rochester, Minnesota. Manuscript received
May 7, 2011; revised manuscript received and accepted June 9, 2011.
This study was supported by Grant 2004219 the South-Eastern Norway
Regional Health Authority and the University of Oslo, Oslo, Norway.
*Corresponding author: Tel: 47-4010-7050; fax: 47-6796-2190.
E-mail address: [email protected] (T. Omland).
0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjcard.2011.06.016

Methods
This is a substudy of the Akershus Sleep Apnea Project
(ASAP). The recruitment protocol and main inclusion and
exclusion criteria have been previously reported.6 In brief,
the Berlin Questionnaire was mailed to 30,000 randomly
selected patients 30 to 65 years of age (Figure 1). The Berlin
Questionnaire includes questions on daytime sleepiness,
snoring, and obesity/hypertension and is used to stratify
patients for risk of OSA. Of the 16,302 responders, 1,772
subjects were further categorized in predefined strata based
on the Berlin Questionnaire and randomly drawn for participation in the clinical phase of the ASAP. In all strata
there was a balanced age and gender distribution, whereas
subjects with previous ear surgery for recurrent otitis media,
cardiovascular disease, and diabetes mellitus were oversampled. Fifty percent to 70% of subjects in each stratum
were considered at high risk of having OSA.
All subjects participating in the clinical phase of the
ASAP were interviewed and subjected to a standardized
clinical examination. Cardiovascular disease was defined as
coronary artery disease (angina, previous myocardial infarction, previous coronary artery intervention), heart failure, or
history of stroke. Data on diabetes mellitus (fasting blood
glucose ⱖ7 mmol/L or antidiabetic medication) and hypertension (systolic blood pressure ⱖ140 mm Hg, diastolic
blood pressure ⱖ90 mm Hg, or on antihypertensive medication) were also recorded. Blood pressure (Dinamap, ProCare 400, GE Healthcare, Milwaukee, Wisconsin) was meawww.ajconline.org

1142

The American Journal of Cardiology (www.ajconline.org)

Figure. Flow chart of inclusion in the study. PSG ⫽ polysomnogram.

sured 3 times with the patient sitting down and the mean of
the last 2 recordings was used for analyses. Body mass
index was measured by dividing weight (kilograms) by
height (meters) squared. Waist– hip ratio was measured by
dividing waist circumference (centimeters) by hip circumference (centimeters). Fasting blood samples were drawn in
the morning after the sleep recordings and lipids were measured by standard laboratory methods.
Participants who agreed to participate in the clinical
phase of the ASAP completed a full in-hospital polysomnographic procedure. Number and duration of apneas and
hypopneas were recorded with Somnologica 3.2 (FlagaMedcare, Buffalo, New York). AHI was calculated by 2
United States board-certified polysomnographic technicians
blinded to Berlin Questionnaire scores and results of Holter
recordings. OSA was defined as an AHI ⱖ5. SaO2 was
recorded by finger plethysmography (Nonin, Plymouth,
Minnesota). The nadir SaO2 was recorded after all results
had been manually checked for technical artefacts.
A 5-channel ambulatory electrocardiograph (MedilogAR12,
Oxford Instruments Medical, Ltd., Surrey, United Kingdom) was fitted to all subjects on arrival during the
midday/afternoon before polysomnographic recordings.
The Holter recorder was retained throughout the examinations, permitting continuous assessment of heart rate
and arrhythmias. Electrocardiograph recordings were automatically interpreted by a software engine (Medilog
Darwin, ScanMed Medical, Gloucestershire, United
Kingdom) and subsequently manually reviewed by 2 re-

Table 1
Overview of arrhythmias
Supraventricular arrhythmias
1. Atrial premature complexes
2. Supraventricular tachycardia
3. Chronic atrial fibrillation
4. Paroxysmal atrial fibrillation
Ventricular arrhythmias
1. Ventricular premature complexes
2. Bigeminy
3. Trigeminy
4. Nonsustained ventricular tachycardia; minimum 3 consecutive
ventricular beats ⱖ110 beats/min
5. Complex ventricular ectopy: bigeminy, trigeminy, or nonsustained
ventricular tachycardia
Conduction delay arrhythmias
1. Sinus pause ⬎2 seconds
2. Atrioventricular block

searchers (S.K.N., G.E.) according to predefined criteria.
Cardiac arrhythmias were divided into supraventricular
arrhythmias, ventricular arrhythmias, and conduction delay arrhythmias (Table 1). Among ventricular arrhythmias, bigeminy, trigeminy, and nonsustained ventricular
tachycardia were also grouped together as complex ventricular ectopies. All arrhythmias were coded as dichotomous outcomes (present or absent) according to acknowledged cutoffs applied in previous communitybased studies.4,5 Ventricular premature complexes were
divided by a cutoff of 5 events/hour (pathologic)4,5 and

Arrhythmias and Conduction Disturbances/Cardiac Arrhythmias in Mild OSA

1143

Table 2
Characteristics of subjects based on obstructive sleep apnea (OSA) status
Variable

OSA

Age (years)
Women
Body mass index (kg/m2)
Waist–hip ratio
Mean heart rate (beats/min)
Current smokers
Hypertension
Diabetes mellitus
Stroke
Heart failure
Angina pectoris
Myocardial infarction
Coronary artery bypass grafting
Percutaneous coronary intervention
Cardiovascular disease*
Triglycerides
mmol/L
mg/dl
Total cholesterol
mmol/L
mg/dl
High-density lipoprotein cholesterol
mmol/L
mg/dl
Platelet aggregation inhibitors
Diuretics
␤ Blocker
Calcium channel blocker
Angiotensin II–converting enzyme inhibitor/angiotensin II receptor blocker
Statin
Apnea–hypopnea index (events/hour)
Nadir oxygen saturation

p Value

No
(n ⫽ 215)

Yes
(n ⫽ 271)

44.1 ⫾ 0.8
57%
27 ⫾ 0.3
0.9 ⫾ 0.01
70.8 ⫾ 0.6
29%
41%
7%
2%
0%
0.5%
4%
0.5%
2%
6%

51.9 ⫾ 0.6
36%
30 ⫾ 0.3
1.0 ⫾ 0.01
72.1 ⫾ 0.6
26%
67%
17%
4%
0%
3%
13%
1.5%
5%
18%

⬍0.001
⬍0.001
⬍0.001
⬍0.001
0.2
0.4
⬍0.001
0.001
0.4
—
0.05
⬍0.001
0.4
0.09
⬍0.001

1.2 (0.9–1.7)
46.4 (34.8–65.7)

1.5 (1.1–2)
58 (42.5–77.3)

⬍0.001

5.4 (4.8–6.2)
208.8 (185.6–239.8)

5.5 (4.8–6.2)
212.7 (185.6–239.8)

0.3

1.3 (1.1–1.6)
50.3 (42.4–61.9)
8.4%
5.1%
8.8%
4.7%
12.6%
11.2%
1.4 (0.5–3.0)
89 ⫾ 0.2

1.3 (1.0–1.5)
50.3 (38.7–58)
22.1%
18.5%
21.8%
13.3%
29.2%
26.6%
16.8 (8.9–32.6)
82 ⫾ 0.4

0.009
⬍0.001
⬍0.001
⬍0.001
0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001

Values are presented as mean ⫾ SEM, percentage of subjects, or median (quartiles 1 to 3).
* Defined as coronary artery disease (angina, previous myocardial infarction, previous coronary artery intervention), heart failure, or history of stroke.
Table 3
Prevalence of arrhythmias according to obstructive sleep apnea (OSA) status and day versus night
Variable

Ventricular premature complexes ⱖ5/hour
Ventricular premature complexes ⱖ30/hour
Nonsustained ventricular tachycardia
Complex ventricular ectopy*
Atrial premature complexes ⱖ5/hour
Atrial fibrillation/paroxysmal atrial fibrillation
Pause ⬎2 seconds

Daytime OSA

Night-Time OSA

No
(n ⫽ 215)

Yes
(n ⫽ 271)

p Value

No
(n ⫽ 215)

Yes
(n ⫽ 271)

p Value

5.1%
1.9%
1.9%
4.7%
48.4%
0%
4.2%

14.0%
5.9%
2.6%
10.7%
41.7%
1.5%
5.9%

0.001
0.036
0.76
0.015
0.14
0.13
0.34

4.7%
1.4%
0.5%
1.9%
49.8%
0%
4.7%

12.2%
5.2%
0.4%
5.5%
49.4%
1.5%
7.7%

0.004
0.026
1.0
0.057
0.94
0.13
0.17

* Defined as bigeminy, trigeminy, or nonsustained ventricular tachycardia.

ⱖ30 events/hour (severe).7 Interpreters were blinded to Berlin Questionnaire scores and polysomnographic results and
scoring was performed separately. The intraclass correlation
coefficient between the 2 reviewers was 0.99 to 1 (n ⫽ 25)
for arrhythmic events measured by Holter recording. For
uncertain classification of an arrhythmia, a third reviewer
(T.O.) was consulted.

Categorical data are presented as absolute numbers and
percentages and continuous data as mean ⫾ SEM (normal
distribution) or median and quartiles 1 to 3 (nonparametric
data). Continuous data were assessed by histograms and normal Q–Q plots to check for normal distribution. Differences
between groups, including prevalence of arrhythmias were
assessed by chi-square test or Fisher’s exact test and by Stu-

1144

The American Journal of Cardiology (www.ajconline.org)

Table 4
Predictors for night-time ventricular premature complexes by univariate and multivariate logistic regression analyses
Night-Time Ventricular Premature Complexes ⱖ5/Hour

Apnea–hypopnea index (per 1-U increase)
Male gender
Age (per 1-year increase)
Hypertension
Diabetes mellitus
Cholesterol/high-density lipoprotein cholesterol ratio (per 1-U increase)
Body mass index (per 1-U kg/m2 increase)
Cardiovascular disease
Smoking

Univariate

Multivariate

OR

95% CI

p Value

Adjusted OR

95% CI

p Value

1.74
1.29
1.06
1.56
0.74
0.95
1.01
3.04
1.03

1.32–2.31
0.68–2.45
1.03–1.09
0.81–3.0
0.25–2.16
0.75–1.20
0.95–1.08
1.47–6.30
0.51–2.07

⬍0.001
0.43
⬍0.001
0.19
0.58
0.68
0.70
0.003
0.93

1.51

1.11–2.04

0.008

1.04

1.0–1.08

0.038

1.83

0.85–3.94

0.12

Apnea– hypopnea index was transformed by natural logarithm before regression analysis.
Table 5
Predictors for daytime ventricular premature complexes by univariate and multivariate logistic regression analyses
Daytime Ventricular Premature Complexes ⱖ5/Hour

Apnea–hypopnea index (per 1-U increase)
Male gender
Age (per 1-year increase)
Hypertension
Diabetes mellitus
Cholesterol/high-density lipoprotein cholesterol ratio (per 1-U increase)
Body mass index (per 1-U kg/m2 increase)
Cardiovascular disease
Smoking

Univariate

Multivariate

OR

95% CI

p Value

Adjusted OR

95% CI

p Value

1.69
1.48
1.09
2.41
1.03
0.97
1.01
3.24
0.95

1.30–2.20
0.80–2.73
1.05–1.13
1.25–4.68
0.42–2.55
0.78–1.20
0.95–1.07
1.63–6.45
0.49–1.86

⬍0.001
0.21
⬍0.001
0.009
0.95
0.77
0.87
0.001
0.89

1.37

1.02–1.82

0.035

1.07
0.93

1.03–1.12
0.44–2.0

⬍0.001
0.86

1.81

0.86–3.82

0.12

Apnea– hypopnea index was transformed by natural logarithm before regression analysis.

dent’s t test or Mann–Whitney U test as appropriate. Correlations were calculated by Spearman rank correlation. For arrhythmias with divergent prevalence in the OSA versus nonOSA group, the association between AHI and arrhythmias was
assessed by univariate and multivariate logistic regression
analyses with results reported as odds ratio (OR) per 1-U
increase of logarithmically transformed AHI and 95% confidence interval (CI). Covariates such as age, gender, body mass
index, diabetes mellitus, hypertension, total cholesterol/highdensity lipoprotein cholesterol ratio, and history of cardiovascular disease were entered into multivariate models if they
were significant in univariate models. In a second set of logistic
regression analyses, AHI was substituted by nadir SaO2 as the
variable assessing OSA severity. A p value ⬍0.05 was considered statistically significant for all analyses. Analyses were
performed with SPSS 16.0 or 18.0 for Windows (SPSS, Inc.,
Chicago, Illinois).
The main protocol and all subprotocols of the ASAP
were approved by the regional ethics committee. The study
was conducted in accordance with the Declaration of Helsinki and all participants signed an informed consent before
study commencement.
Results
In total, 535 participants were included in the clinical phase
of the study (Figure 1). Of these, 49 subjects were excluded
because of unsatisfactory polysomnographic recordings or
technical problems with Holter registration. Baseline charac-

teristics of subjects with and without OSA are presented in
Table 2. In general, subjects diagnosed with OSA were older,
more obese, and more likely to be men compared to subjects
without OSA. Subjects with OSA also exhibited a higher
prevalence of co-morbidities including hypertension, diabetes
mellitus, and previous myocardial infarction, and the difference in co-morbidities was also reflected in medication use.
Of the 486 subjects included in the final analysis (Figure
1), 271 subjects (56%) were diagnosed with OSA. Only 72
subjects (14.8%) were diagnosed with severe OSA as defined by AHI ⱖ30. AHI correlated with established risk
factors for OSA such as age (r ⫽ 0.40), body mass index
(r ⫽ 0.35), and waist– hip ratio (r ⫽ 0.48, p ⬍0.001 for all
comparisons). Subjects with OSA had lower SaO2 during
sleep compared to subjects without OSA as evaluated by the
recorded nadir SaO2.
Median Holter recording time was 18.5 hours (quartiles
1 to 3 17 to 20). A larger proportion of subjects with OSA
had ventricular premature complexes at night and during the
day compared to subjects without OSA (Table 3). This was
also evident when examining the proportion of subjects
exhibiting severe ventricular premature complex activity
(ⱖ30/hour) at night and during the day. There was a higher
prevalence of complex ventricular ectopies during daytime
recordings in subjects with OSA. For conduction delay
arrhythmias and supraventricular arrhythmias including
atrial fibrillation, we found no differences between the OSA
and non-OSA groups (Table 3).

Arrhythmias and Conduction Disturbances/Cardiac Arrhythmias in Mild OSA

By logistic regression analysis a 1-U increase in logarithmically transformed AHI was associated with increased
prevalence of ventricular premature complexes at night and
during the day (Tables 4 and 5). By multivariate analysis,
after adjusting for clinical relevant confounders, this association was still significant.
In a second set of analyses that substituted AHI with
nadir SaO2 as the OSA variable, normal SaO2 during sleep
was associated with a lower prevalence of ventricular premature complexes at night (OR per 1-U increase in SaO2
0.94, 95% CI 0.90 to 0.98, p ⫽ 0.002) and during the day
(OR 0.94, 95% CI 0.91 to 0.98, p ⫽ 0.002). The inverse
association between SaO2 and prevalence of ventricular
premature complexes was, however, no longer evident in
multivariate analysis for daytime or night-time recordings
(p ⫽ 0.065 for night and p ⫽ 0.18 for day).
Multivariate analyses were not performed on severe ventricular premature complex activity (ⱖ30/hour) or complex
ventricular ectopies because of the small number of events
(n ⫽ 17 to 38).
Discussion
The principal findings of this study are that OSA of
mainly mild and moderate severity is associated with an
increased prevalence of ventricular arrhythmias in middleaged subjects and that high AHI is independently associated
with frequent ventricular premature complexes in analyses
that adjusted for relevant covariates.
Our results are in line with results previously reported for
patients with severe OSA. The first reports of an association
between OSA and cardiac arrhythmias were in patients
recruited from sleep clinics.1,2,8 These studies included a
selected group of patients with severe OSA as reflected by
mean AHIs of 38 to 42. Also, 1 sleep clinic-based study has
reported increased risk of arrhythmias even in patients with
mild OSA, suggesting a graded risk for arrhythmias depending on OSA severity.9 Recent publications from the Sleep
Heart Health Study5 and the Outcomes of Sleep Disorders
in Older Men Study4 have supplemented the early results
and have reported a high rate of cardiac arrhythmias in
patients with OSA from the general population. Nevertheless, because of inclusion of only elderly men in the Outcomes of Sleep Disorders in Older Men Study (mean age 76
years) and elderly patients with more severe OSA in the
Sleep Heart Health Study (mean age 71 years), these results
may not be applicable to all patients with OSA in the
community. Our results are therefore important because
they complement and transcend previous reports by showing that even middle-aged subjects with OSA exhibit an
increased prevalence of ventricular premature complexes
compared to subjects with normal breathing during sleep.
Because a considerable portion of subjects with OSA in the
general population are middle-aged and have unrecognized
and less severe OSA,10,11 our results are more directly
relevant to a large group of patients with OSA in the
community.
We found evidence of increased incidence of ventricular
arrhythmias in OSA, whereas frequency of conduction delay arrhythmias and supraventricular arrhythmias including
atrial fibrillation was low and not associated with OSA in

1145

our participants. In contrast to our results, the Outcomes of
Sleep Disorders in Older Men Study and the Sleep Heart
Health Study reported an increased prevalence of atrial
fibrillation in patients with OSA. The lower prevalence of
atrial fibrillation in our study is most likely a result of the
younger cohort because the prevalence of atrial fibrillation
markedly increases with age.12 In general, our participants
also exhibited a lower prevalence of cardiac arrhythmias
compared to other reports and this can be attributed to a
relatively young cohort with milder OSA.
The increased frequency of severe ventricular premature
complexes we report in subjects with OSA may have particular clinical relevance because this has been found to be
independently associated with future myocardial infarction
and cardiovascular mortality in subjects free from cardiovascular disease at baseline.7,13 Increased mortality in patients with OSA,14 –16 particularly at night,17 emphasizes the
importance of identifying possible mechanisms by which
OSA could affect myocardial electrical stability. The independent association between severity of OSA, as reflected
by AHI, and ventricular arrhythmias in our study indicates
a possible contribution by OSA to ventricular arrhythmias
and potential mechanisms for this effect are night-time
hypoxemia, increased sympathetic tone, acidosis, and alterations in intrathoracic pressure during sleep.18 –20
An important strength of this study is the inclusion of
younger subjects with less severe OSA reflecting a large
proportion of subjects with OSA in the general population.
By also obtaining information on daytime arrhythmias, our
study provides a complete picture of cardiac arrhythmias in
OSA. An important limitation of the study is the lack of
cardiac imaging data. There are baseline differences between the OSA and non-OSA groups and we cannot rule out
pre-existing differences in structural heart disease. We have,
however, tried to compensate for this statistically by including history of cardiovascular disease in multivariate models.
We acknowledge that because of day-to-day variability in
the frequency of arrhythmias 24-hour electrocardiographic
recordings may not accurately reflect the actual severity of
arrhythmias in our participants.
Acknowledgment: We thank the staff at Akershus University Hospital, Department Stensby, and the other researchers
of the ASAP who contributed to the project.
1. Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and
conduction disturbances during sleep in 400 patients with sleep apnea
syndrome. Am J Cardiol 1983;52:490 – 494.
2. Hoffstein V, Mateika S. Cardiac arrhythmias, snoring, and sleep apnea. Chest 1994;106:466 – 471.
3. Tilkian AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons
FB, Dement WC. Sleep-induced apnea syndrome. Prevalence of cardiac arrhythmias and their reversal after tracheostomy. Am J Med
1977;63:348 –358.
4. Mehra R, Stone KL, Varosy PD, Hoffman AR, Marcus GM, Blackwell
T, Ibrahim OA, Salem R, Redline S. Nocturnal arrhythmias across a
spectrum of obstructive and central sleep-disordered breathing in older
men: outcomes of sleep disorders in older men (MrOS sleep) study.
Arch Intern Med 2009;169:1147–1155.
5. Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner
HL, Sahadevan J, Redline S; Sleep Heart Health Study. Association of
nocturnal arrhythmias with sleep-disordered breathing: the Sleep Heart
Health Study. Am J Respir Crit Care Med 2006;173:910 –916.

1146

The American Journal of Cardiology (www.ajconline.org)

6. Hrubos-Strom H, Randby A, Namtvedt SK, Kristiansen HA, Einvik G,
Benth J, Somers VK, Nordhus IH, Russell MB, Dammen T, Omland
T, Kvaerner KJ. A Norwegian population-based study on the risk and
prevalence of obstructive sleep apnea. The Akershus Sleep Apnea
Project (ASAP). J Sleep Res 2011;20:162–170.
7. Sajadieh A, Nielsen OW, Rasmussen V, Hein HO, Frederiksen BS,
Davanloul M, Hansen JF. Ventricular arrhythmias and risk of death
and acute myocardial infarction in apparently healthy subjects of age
⬎ or ⫽55 years. Am J Cardiol 2006;97:1351–1357.
8. Olmetti F, La Rovere MT, Robbi E, Taurino AE, Fanfulla F. Nocturnal
cardiac arrhythmia in patients with obstructive sleep apnea. Sleep Med
2008;9:475– 480.
9. Abe H, Takahashi M, Yaegashi H, Eda S, Tsunemoto H, Kamikozawa
M, Koyama J, Yamazaki K, Ikeda U. Efficacy of continuous positive
airway pressure on arrhythmias in obstructive sleep apnea patients.
Heart Vessels 2010;25:63– 69.
10. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc
Am Thorac Soc 2008;5:136 –143.
11. Young T, Evans L, Finn L, Palta M. Estimation of the clinically
diagnosed proportion of sleep apnea syndrome in middle-aged men
and women. Sleep 1997;20:705–706.
12. Lafuente-Lafuente C, Emery C, Laurendeau C, Fagnani F, Bergmann
JF. Long term treatment of atrial fibrillation in elderly patients: a
decision analysis. Int J Cardiol 2010. [Epub ahead of print].
13. Massing MW, Simpson RJ Jr, Rautaharju PM, Schreiner PJ, Crow
R, Heiss G. Usefulness of ventricular premature complexes to
predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort). Am J Cardiol 2006;98:
1609 –1612.

14. Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein
RR. Sleep apnea as an independent risk factor for all-cause mortality:
the Busselton Health Study. Sleep 2008;31:1079 –1085.
15. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ,
Stubbs R, Hla KM. Sleep disordered breathing and mortality: eighteenyear follow-up of the Wisconsin sleep cohort. Sleep 2008;31:1071–
1078.
16. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with
or without treatment with continuous positive airway pressure: an
observational study. Lancet 2005;365:1046 –1053.
17. Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of
sudden death in obstructive sleep apnea. N Engl J Med 2005;352:
1206 –1214.
18. Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural
mechanisms in obstructive sleep apnea. J Clin Invest 1995;96:1897–
1904.
19. Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A,
Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R,
Woo M, Young T. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation
Scientific Statement from the American Heart Association Council for
High Blood Pressure Research Professional Education Committee,
Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. J Am Coll Cardiol 2008;52:686 –717.
20. Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK.
Sympathetic activity in obese subjects with and without obstructive
sleep apnea. Circulation 1998;98:772–776.