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Journal of Cardiac Failure Vol. 17 No.

5 2011

High Prevalence of Sleep Apnea in Heart Failure Outpatients:


Even in Patients With Preserved Systolic Function
TOBIAS E. HERRSCHER, MD,1 HARRIET AKRE, MD, PhD,2 BRITT VERLAND, PhD,2 LEIV SANDVIK, PhD,3
AND ARNE S. WESTHEIM, MD, PhD4
Oslo, Norway

ABSTRACT
Background: Sleep-disordered breathing (SDB) is common in patients with reduced ejection fraction
(EF). However, little is known about the prevalence of SDB in a general heart failure population including
patients with preserved EF (HFPEF).
Methods: We prospectively enrolled stable heart failure outpatients from our heart failure clinic to assess
the prevalence of SDB independent of systolic left ventricular function.
Results: Among 115 patients (62% with reduced EF, 38% with preserved EF, New York Heart Association Class II-IV) SDB was present in 81% (27% central sleep apnea, 54% obstructive sleep apnea
[OSA]). HFPEF patients had SDB in 80% of the cases, 62% had OSA. This group had significantly
more hypertension.
Conclusions: This study shows a high prevalence of SDB in a general heart failure population, also in
patients with HFPEF. These patients have predominantly OSA. Especially in patients with HFPEF
SDB should be kept in mind and referral to a sleep specialist should be considered. (J Cardiac Fail
2011;17:420e425)
Key Words: Sleep-disordered breathing, obstructive sleep apnea, preserved ejection fraction.

Chronic heart failure (HF) represents a common and serious health problem. Incidence and prevalence are on the
rise.1 Patients with clinical symptoms of HF are a heterogeneous group. Approximately 40% have HF with preserved
ejection fraction (HFPEF), increasing with age.2 The prognosis for chronic HF continues to be serious with a 1-year
mortality rate of 30%.3 Survival rates of HFPEF patients
seems to be better than in patients with reduced ejection
fraction (EF), but are still high with a mortality rate of
more than 30% within 4 years.4

Sleep-disordered breathing (SDB) is commonly seen in


patients with reduced left ventricular function. In recent
larger studies prevalence rates of 50 to 81% were documented in this group.5e8 SDB seems to be highly prevalent
in HFPEF patients as well.9,10
However, little is known about the prevalence of SDB in
a general HF population.
The purpose of this study was to prospectively evaluate
the prevalence and characteristics of SDB in outpatients
treated in a Norwegian HF clinic independent of left ventricular systolic function.
Materials and Methods

From the 1Department of Cardiology, Lovisenberg Diakonale Sykehus,


Oslo, Norway; 2Unit of Sleep Medicine, Lovisenberg Diakonale Sykehus,
Oslo, Norway; 3Department of Biostatistics, Oslo University Hospital
Ullev
al, Norway and 4Department of Cardiology, Oslo University Hospital
Ullev
al, Norway.
Manuscript received September 23, 2010; revised manuscript received
January 27, 2011; revised manuscript accepted January 28, 2011.
Reprint requests: Tobias E. Herrscher, MD, Lovisenberg Diakonale Sykehus, Department of Cardiology, Lovisenberggata 17, 0440 Oslo, Norway. Tel: 47 23226144. E-mail: tehb@lds.no
Supported by the research council at Lovisenberg Diakonale Sykehus.
See page 424 for disclosure information.
1071-9164/$ - see front matter
2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.cardfail.2011.01.013

Selection of Population
Patients were consecutively enrolled from the outpatient HF
clinic of Lovisenberg Diakonale Sykehus in a time period between
June 2006 and December 2008. The diagnosis of HF was defined
by clinical signs and symptoms, measurement of NT-proBNP, and
assessment of left ventricular function according to the American
College of Cardiology/American Heart Association and European
Society of Cardiology guidelines.11,12 Subjects were included if
they had clinically stable HF and their medication fully uptitrated
as recommended in the HF guidelines.11,12 Further inclusion criteria were: New York Heart Association (NYHA) functional Class

420

High Prevalence of Sleep Apnea in Heart Failure Outpatients


II-IV and age between 18 and 80 years. Subjects were excluded if
they had been hospitalized of any reason or needed intravenous diuretics within the previous 6 weeks. Further exclusion criteria
were chronic obstructive pulmonary disease (COPD) in stage III
and IV according to the Global Initiative for Chronic Lung Disease
and myocardial infarction or stroke within the previous 3 months.
All patients gave written informed consent. The study was reviewed and approved by the Regional Ethics committee and the
bureau of Protection of Personal Privacy.

Herrscher et al

421

Statistics
Statistical analyses were performed using SPSS (version 17.0)
software (SPSS Inc. Chicago, IL). Differences between groups
were assessed using the unpaired Students t-test for parametric results and the Mann-Whitney rank sum test for nonparametric data.
Chi-square test was used to compare proportions between groups.
A value of P ! .05 was considered statistically significant.

Results
Evaluated Parameters
Comorbidity data, NYHA functional class, current medication,
body mass index (BMI), age, sex, and etiology of HF, as registered
in our HF database, were used for statistical analysis. All patients
had 2-dimensional echocardiographic assessment of left ventricular EF. EF was determined by using the apical four chamber view,
Simpsons method. Parasternal M-mode and Doppler recordings
were done to complete the echocardiographic examination. The
latest EF measurement after uptitration of HF medication was
used for study purpose. The mean time interval from echo to sleep
study was 3 to 4 months. Patients with EF $45% were considered
to be in the HFPEF group. Parameters of diastolic function were
not available on all patients.
Subjects were assessed with 2 questionnaires the same day the
sleep study was performed: The Epworth Sleepiness Scale (ESS)
and The Minnesota Living with Heart Failure Questionnaire
(MLHFQ).
Blood samples were obtained the morning after the sleep study.
Subjects were fasting for at least 8 hours.

Patient Characteristics

A total of 115 patients (24 females, 91 males) were enrolled into the study; 120 patients met the inclusion criteria
and 5 subjects refused to participate because of reasons of
inconvenience. Sixty-two percent of our population had reduced EF, 38% were patients with HFPEF. The baseline
characteristics between these 2 groups were significantly
different in etiology of HF and NYHA class. Patients
with reduced EF had a higher N-terminal prohormone brain
natriuretic peptide (NT-proBNP) and used more bblockers, angiotensin-converting enzyme (ACE) inhibitors
or angiotensin receptor blockers (ARBs), diuretics, and
aldosterone-antagonists. Patients with HFPEF had significantly more hypertension. There were no significant differences in sex, age, BMI, quality of life, or sleepiness
(Table 1).
SDB

Cardiorespiratory Polygraphy
Subjects underwent an in-home, unattended overnight polygraphy with a standard 10-channel recording device (Embletta, ResMed, Norway). Nasal air flow (nasal pressure transducer),
thoracic and abdominal movements (respiratory inductance plethysmography), pulse oximetry, body position, and a 3-channel electrocardiogram were recorded continuously. Data were downloaded
and scored at the sleep laboratory, Lovisenberg by 1 single qualified SDB specialist, using Somnologica for Embletta software
(Medcare, Embla, the Netherlands).
A modified version of the 2007 American Academy of Sleep
Medicine criteria for scoring respiratory events was used.13 Obstructive apnea was defined as a $10 seconds cessation of airflow
as measured by nasal pressure associated with the continuation of
thoracic and abdominal effort. Central apnea was defined as $10
seconds cessation of airflow without thoracic and abdominal effort. Hypopnea was defined as a 50% reduction in airflow with either a $3% oxyhemoglobin desaturation or a presumed arousal, as
defined by 10% increase in heart rate. The apnea-hypopnea index
(AHI) was calculated based on total number of events per hour of
total recording time, movement time omitted. SDB was defined as
mild by AHI O5, moderate by AHI $15, and severe by AHI $30.
Another metric of central sleep apnea was also used to define primary Cheyne-Stokes respiration. This is defined as a symmetrical
crescendo-decrescendo respiratory pattern with a O50% difference between peak and nadir nasal pressure or respiratory effort
amplitude, occurring within a 30 to 90-second period. There had
to be at least 3 cycles of Cheyne-Stokes respiratory pattern in
a row and with duration of at least 10 consecutive minutes. Patients with both obstructive and central apneas were classified according to the dominating respiratory sleep pattern.

The overall prevalence of SDB in our HF cohort was


81%. Twenty-seven percent of patients had central sleep apnea with Cheyne-Stokes respiration (central sleep apnea;
CSA) and 54% had obstructive sleep apnea (OSA) (AHI
$5/h). Considering the severity of SDB, moderate to severe
SDB (AHI $15/h) was present in 52% of the cases (23%
CSA, 29% OSA; Fig. 1).
Table 2 shows the characteristics of patients with OSA/
CSA versus those without SDB. The patients with OSA/
CSA had significantly higher HbA1c levels and significantly less mild to moderate COPD. We could not show
any differences in EF, quality of life, or sleepiness between
the patients with and without SDB.
Patients With Preserved EF versus Reduced EF

Patients with HFPEF had nearly the same high prevalence of sleep apnea as the group with reduced EF (80%
vs. 82%), Figure 2. This group had more OSA than CSA,
62% vs. 18%. Subjects with HFPEF and OSA had a higher
BMI (32.0 6 5.8 vs. 27.9 6 4.1, P 5 .02) and more likely
hypertension (74% vs. 35%, P 5 .01) compared with patients with HFPEF without OSA.
Discussion
SDB

This study shows a high prevalence of SDB in a general outpatient HF population treated in a Norwegian

422 Journal of Cardiac Failure Vol. 17 No. 5 May 2011


Table 1. Baseline Characteristics of the Study Group

Age (y)
Sex female/male
BMI (kg/m2)
LVEF (%)
NT-proBNP (pg/mL)
Hemoglobin (mg/dL)
HbA1c (%)
Creatinine (mg/dL)
Cholesterol (mg/dL)
NYHA, n (%)
Class II
Class III IV
CRT
MLHFQ
Epworth SS
Etiology
Ischemic
Nonischemic
b-blockers
ACE inhibitor/ARBs
Diuretics
Spironolactone
Digitoxin
Comorbidity
Hypertension
Atrial fibrillation
Diabetes
Stroke
COPD

Total (n 5 115)

Reduced EF (n 5 71)

HFPEF (n 5 44)

62.0 6 9.7
24/91
29.1 6 5.5
38.1 6 13.0
1615 6 2173
14.2 6 1.4
6.2 6 1.1
1.1 6 0.4
174 6 50

61.4 6 9.5
11/60
28.4 6 5.3
29.6 6 8.2
2216 6 2478
14.3 6 1.4
6.4 6 1.4
1.1 6 0.4
170 6 50

62.8 6 10.0
13/31
30.4 6 5.5
51.7 6 5.2*
507 6 474*
14.1 6 1.5
6.0 6 0.8
1.1 6 0.4
182 6 50

89 (77%)
26 (23%)
3 (2%)
42 6 26
5.8 6 4.0

47 (66%)
24 (24%)
3 (4%)
44 6 27
5.6 6 4.0

42 (95%)*
2 (5%)*
0
39 6 24
6.1 6 4.1

63
52
104
106
90
15
15

(55%)
(45%)
(90%)
(92%)
(78%)
(13%)
(13%)

52
19
68
69
61
13
11

(73%)
(27%)
(96%)
(97%)
(86%)
(18%)
(16%)

11
33
35
37
29
2
8

(25%)*
(75%)*
(80%)*
(84%)*
(66%)*
(5%)*
(18%)

47
44
28
12
20

(41%)
(38%)
(24%)
(10%)
(17%)

21
23
17
7
12

(30%)
(32%)
(24%)
(9%)
(17%)

26
21
11
5
8

(59%)*
(48%)
(25%)
(11%)
(18%)

ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BMI, body mass index; COPD, chronic obstructive lung disease; CRT, cardiac
resynchronization therapy; EF, ejection fraction; Epworth SS, Epworth sleepiness scale; HFPEF, heart failure with preserved ejection fraction; LVEF, left
ventricular ejection fraction; MLHFQ, Minnesota living with heart failure questionnaire; NT-proBNP, N-terminal prohormone brain natriuretic peptide;
NYHA, New York heart association.
Data presented as mean 6 standard deviation or percentage.
*P ! .05, reduced EF vs. HFPEF.

heart failure clinic. Our patients were referred either directly by their primary physicians or by the medical department at the local hospital, reducing the possible
patient selection bias seen at tertiary academic centers.
Despite this, our data are consistent with the large scale
studies of Oldenburg and Bitter et al.6,9 That there
were more males than females can be explained by

a referral bias but is not different from other HF clinics


in Norway.14
The usage of b-blockers and ACE-inhibitors/ARBs was
higher than in recently published prevalence studies in patients with SDB.8,15 b-blocker usage is negatively correlated with the prevalence and severity of SDB.16,17 By the
time the sleep study was performed, patients were in

Prevalence of SDB in a stable heart failure population independent of LVEF


100 %
90 %
80 %
70 %

27 %

60 %
CSA

50 %

OSA
23 %

40 %
30 %

54 %

20 %
29 %

10 %
0%
AHI > 5

AHI >= 15

Fig. 1. Prevalence of sleep-disordered breathing in a stable heart failure population independent of left ventricular ejection fraction. AHI,
apnea-hypopnea index; OSA, obstructive sleep apnea.

High Prevalence of Sleep Apnea in Heart Failure Outpatients

Herrscher et al

423

Table 2. Clinical Characteristics of Subjects With SDB versus Those Without SDB

Age (y)
Sex (female/male)
BMI (kg/m2)
AHI (events/h)
ODI (events/h)
Mean O2 (%)
Lowest O2 (%)
LVEF (%)
CRT
NT-proBNP (pg/mL)
Hemoglobin (mg/dL)
HbA1c (%)
Creatinine (mg/dL)
Cholesterol (mg/dL)
NYHA, n
Class II
Class III IV
MLHFQ
Epworth SS
Etiology
Ischemic
Nonischemic
b-blockers
ACE inhibitor/ARBs
Diuretics
Spironolactone
Digitoxin
Comorbidity
Hypertension
Atrial fibrillation
Diabetes
Stroke
COPD

OSA (n 5 62)

CSA (n 5 31)

No SDB (n 5 22)

62.4 6 9.2
15/47
30.2 6 6.0*
25.0 6 21.7*
26.6 6 22.3*
92.5 6 2.8*
78.0 6 7.3*
40.4 6 13.2y
3 (4%)
1294 6 1945
14.1 6 1.5
6.3 6 1.1*
1.0 6 0.3y
178 6 43

62.2 6 10.6
3/28
28.4 6 4.2
26.8 6 13.1*
27.8 6 14.2*
93.5 6 1.7*
81.6 6 6.7*
34.0 6 12.5
0
2181 6 2326
14.7 6 1.4*
6.6 6 1.3*
1.2 6 0.4
170 6 62

60.2 6 10.0
6/16
27.1 6 4.8
2.3 6 1.5
4.6 6 4.4
94.5 6 1.8
87.4 6 3.0
37.3 6 12.0
0
1691 6 2453
13.8 6 1.3
5.9 6 0.3
1.2 6 0.5
170 6 54

46 (74%)
16 (26%)
40.4 6 27.4
5.9 6 4.3

23 (74%)
8 (26%)
44.3 6 24.1
6.2 6 3.9

20 (91%)
2 (9%)
44.1 6 25.8
5.0 6 3.2

32
30
56
56
47
7
13

(52%)
(48%)
(90%)
(90%)
(76%)
(11%)
(21%)

19
12
26
28
27
4
3

(61%)
(39%)
(84%)
(90%)
(87%)
(13%)
(10%)

12
10
21
22
16
4
3

(55%)
(45%)
(96%)
(100%)
(73%)
(18%)
(14%)

33
24
15
5
10

(53%)*,y
(39%)
(24%)
(8%)
(16%)*

8
13
8
3
1

(26%)
(42%)
(26%)
(10%)
(3%)*

6
7
5
3
9

(27%)
(32%)
(23%)
(14%)
(41%)

ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; AHI, apnea hypopnea index; BMI, body mass index; COPD, chronic obstructive lung disease; CRT, cardiac resynchronization therapy; CSA, central sleep apnea; Epworth SS, Epworth sleepiness scale; LVEF, left ventricular ejection
fraction; MLHFQ, Minnesota living with Heart Failure Questionnaire; NT-proBNP, N-terminal prohormone brain natriuretic peptide; NYHA, New York heart
association; ODI, oxygen desaturation index; SDB, sleep-disordered breathing.
Data presented as mean 6 standard deviation or percentage.
*P ! .05, OSA/CSA vs. no SDB.
y
P ! .05, OSA vs. CSA.

a clinically stable condition, supported by low average NTproBNP levels. Acute heart failure decompensation was
one of the exclusion criteria. Despite these facts, we still

find this high number of SDB, even equal to what has


been reported in acutely decompensated heart failure
patients.18

SDB in patients with reduced and preserved ejection fraction


100 %
90 %
80 %
18 %

70 %
32 %
60 %

CSA

50 %

OSA

40 %
62 %

30 %
20 %

49 %

10 %
0%
red EF

HFPEF

Fig. 2. Sleep-disordered breathing in patients with reduced and preserved ejection fraction. AHI, apnea-hypopnea index; EF, ejection fraction; HFPEF, heart failure with preserved EF; OSA, obstructive sleep apnea.

424 Journal of Cardiac Failure Vol. 17 No. 5 May 2011


Hypoxemia in patients with acute lung congestion together with prolonged circulation time in a condition with
low cardiac output is known to initiate Cheyne-Stokes respiration cycles. Because of these pathophysiological mechanisms, CSA is supposed to be a marker of the severity of
HF.6 However, we still find Cheyne-Stokes respiration in
32% of clinically stable patients with reduced EF and
even in 18% of patients in the HFPEF group.
Overall, this can support the contention that CSA is not
only a consequence of severe heart failure. It seems to be
more a concomitant factor that may contribute to the development of more symptomatically overt HF and can affect
the overall outcome.19,20
Patients with sleep apnea did not evaluate themselves as
sleepy according to the ESS. Additionally, no significant
difference was observed between the groups with and without SDB. An explanation for this might be that the ESS is
a weak instrument to measure sleepiness in patients with
chronic HF.21,22 Patients were reporting a moderate quality
of life according to the MLHFQ23 showing no difference
for SDB status. Reduced quality of life might be one of
the reasons why sleepiness is not perceived as predominant
as it would be in an otherwise healthy population.
SDB is associated with impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes, independent
of obesity.24 It can lead to impairments of insulin sensitivity
and pancreatic b-cell function.25 Patients with both OSA
and CSA had significantly higher HbA1c levels than patients with a normal breathing pattern. SDB may contribute
to a worsening of the glycemic control in our patients with
diabetes. In the SDB group there were more diabetics, but
without being statistically significant.
Patients with mild to moderate COPD were not excluded
from our study. Seventeen percent of our heart failure population had COPD, which is in accordance with numbers
from the Norwegian heart failure registry.26 In other heart
failure populations, the prevalence has been reported as
17 to 27%,27,28 which makes COPD a significant concomitant diagnosis in heart failure. Data support a similar prevalence of OSA in patients with COPD as in an equivalent
general population.29,30
We found just 1 patient with mild to moderate COPD to
have CSA. We did not measure individual partial pressure
of carbon dioxide (pCO2) levels in this study, but pCO2
levels in the upper range of normal in these patients might
prevent the initiation of Cheyne-Stokes respiration cycles in
this group.
HFPEF Group

In contrast to HF patients with reduced systolic function, sleep data are rare in patients with HFPEF. A prevalence of SDB of 80% in patients with HFPEF in our
study is high and equal to the patients with reduced systolic function. Our findings are in accordance with the results of Bitter al, who in the first large scale prevalence
study in 244 patients with HFPEF observed a prevalence

of 69%.9 As in our study, the majority of the patients


had OSA. Bitter et al included their patients attending
a tertiary academic referral unit, in contrast to our study
where the patients were recruited from a local hospital
with referrals mainly from primary physicians. However,
the demographic data of the patients in the 2 studies
show great similarities regarding age, gender, NYHA
class, and heart failure medications.
These patients have a significant higher BMI, which is
a well-established predictor of SDB.31 OSA is considered
an independent risk factor for hypertension.32 In our study
group, we found a significantly higher percentage of hypertension in HFPEF patients with OSA. OSA is also associated with atrial fibrillation33 and impaired diastolic
function.34 Based on these facts, OSA seems to contribute
to the development of HF in patients with HFPEF. Early diagnosis and treatment of OSA according to existing guidelines may prevent worsening or even establishing heart
failure symptoms.
Conclusion
SDB is highly prevalent in a general HF population, independent of left ventricular systolic function. Patients
with HFPEF have predominantly OSA. Especially in this
group, SDB should be kept in mind and referral to a sleep
specialist should be considered.
Disclosures
None.

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