Download Left Ventricular Systolic Dysfunction in Patients

Left Ventricular Systolic Dysfunction in
Patients With Obstructive Sleep Apnea
Syndrome*
Jean-Pierre Laaban, MD, FCCP; Sophie Pascal-Sebaoun, MD;
Evelyne Bloch, MD; Elizabeth Orvoën-Frija, MD; Jean-Michel Oppert, MD; and
Gérard Huchon, MD, FCCP
Study objectives: Conflicting results have been reported regarding the effects of obstructive sleep
apnea syndrome (OSAS) on daytime left ventricular (LV) systolic function. This study aimed to
assess the prevalence and causes of LV systolic dysfunction, using radionuclide angiography, in a
large group of patients with OSAS.
Design and setting: A prospective study in the pneumology department of a university medical
center.
Patients: One hundred sixty-nine consecutive patients with OSAS diagnosed by polysomnography,
hospitalized for the administration of nasal continuous positive airway pressure. Patients with a
known cardiac disease were excluded.
Measurements: LV ejection fraction (LVEF) was measured in all patients, using radionuclide
ventriculography with multiple-gated equilibrium cardiac imaging. Myocardial scintigraphy with
a dipyridamole stress test and echocardiography were performed in those patients with LV
systolic dysfunction, defined by a LVEF < 50%, to detect silent heart disease, especially coronary
artery disease.
Results: LV systolic dysfunction was observed in 7.7% (13 of 169 patients). In these 13 patients,
the mean ⴞ SD LVEF was 42 ⴞ 6%, the lowest value of LVEF was 32%, and no silent cardiac
disease was revealed. Age, body mass index, apnea-hypopnea index, parameters of nocturnal
oxyhemoglobin desaturation, and prevalence of systemic hypertension did not significantly differ
between patients with LVEF < 50% and those with LVEF > 50%. In seven patients with LV
dysfunction, LVEF was measured following treatment of OSAS and reached normal values.
Conclusion: OSAS may be a direct cause of daytime LV systolic dysfunction that can resolve
following reversal of nocturnal apneas.
(CHEST 2002; 122:1133–1138)
Key words: left ventricular ejection fraction; left ventricular function; obstructive sleep apnea syndrome; positive airway
pressure; radionuclide ventriculography.
Abbreviations: ACE ⫽ angiotensin-converting enzyme; AHI ⫽ apnea-hypopnea index; AI ⫽ apnea index;
BMI ⫽ body mass index; CPAP ⫽ continuous positive airway pressure; LV ⫽ left ventricular; LVEF ⫽ left ventricular
ejection fraction; OSAS ⫽ obstructive sleep apnea syndrome; Sao2 ⫽ arterial oxyhemoglobin saturation; TST ⫽ total
sleep time
bstructive sleep apneas are associated with an
O acute
increase in left ventricular (LV) afterload
that can result in acute LV systolic dysfunction.1–3
However, conflicting results have been published
regarding the effects of obstructive sleep apneas on
*From the Departments of Pneumology (Drs. Laaban, PascalSebaoun, Orvoën-Frija, and Huchon), Nuclear Medicine (Dr.
Bloch), and Nutrition (Dr. Oppert), Hotel-Dieu Hospital, Paris,
France.
Manuscript received July 26, 2001; revision accepted April 8,
2002.
Correspondence to: Jean-Pierre Laaban, MD, FCCP, Department
of Pneumology, Hotel-Dieu Hospital, 1, place du Parvis NotreDame, 75181 Paris Cedex 04, France; e-mail: j-pierre.laaban@
htd.ap-hop-paris.fr
www.chestjournal.org
daytime LV systolic function. In a canine model of
obstructive sleep apnea syndrome (OSAS), a significant decrease in LV ejection fraction (LVEF) was
demonstrated with two-dimensional echocardiography after a 1- to 3-month period of OSAS.1 Malone
and coworkers4 showed, in patients with idiopathic
dilated cardiomyopathy and severe OSAS, that daytime LVEF increased significantly after 4 weeks of
nasal continuous positive airway pressure (CPAP)
therapy. Yet several cross-sectional studies5– 8 demonstrated that daytime LVEF was normal in patients
with OSAS, and did not significantly differ between
patients with OSAS and nonapneic control subjects.
The relevance of these studies is hampered by
CHEST / 122 / 4 / OCTOBER, 2002
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1133
several factors: the number of OSAS patients was
small, ranging from 15 to 30 patients5– 8; LV systolic
function was assessed in most studies5,6,8 by echocardiography, which is associated with a high risk of
technical failure in patients with severe obesity9;
patients with systemic hypertension were excluded,5,8 although hypertension is a well-recognized
complication of OSAS10 –14 that may induce LV
dysfunction; and patients with awake hypoxemia
and/or hypercapnia were excluded,5,8 although these
patients have been reported to have more profound
nocturnal oxyhemoglobin desaturation and/or more
severe obesity, which may theoretically affect LV
function.15 The aim of this study was to assess the
prevalence and potential causes of LV systolic dysfunction, using radionuclide angiography, in a large
group of patients with OSAS with no associated
cardiac diseases.
Materials and Methods
⬎ 50% associated with an Sao2 drop of ⱖ 4% for at least 10 s.
The AHI was calculated as the number of apneas and hypopneas
per hour of sleep. Several parameters of oxyhemoglobin desaturation were computed: (1) minimal Sao2; (2) percentage of total
sleep time (TST) spent at Sao2 ⬍ 90%; and (3) percentage of
TST spent at Sao2 ⬍ 80%.
Radionuclide Ventriculography
Multiple-gated equilibrium cardiac imaging was performed
following standard procedure: 1 gigabecquerel of technetium Tc
99m was injected after in vivo RBC labeling. Data were acquired
in the left anterior oblique view, using a degree of obliquity that
provided the best separation between both ventricles and the
atria. Sixteen frames per cycle were obtained (minimum of
200,000 counts per frame, matrix 64 ⫻ 64, Tomo camera Elscint
609 or Elscint Helix; Elscint; Haifa, Israel) and processed with a
special computer system (Elscint Apex SP 1; Elscint).
LVEF was calculated with both automatic and semiautomatic
programs, after generation of Fournier phase and amplitude
images, and a definition of end-diastolic and end-systolic left
ventricular images. LV systolic dysfunction was defined by a
LVEF of ⬍ 50%. The physician who interpreted the radionuclide
scans was aware that the patient had sleep apnea syndrome, but
he had no knowledge of polysomnographic data.
Patients
Evaluation of Cardiovascular Risk Factors
The study population included patients with OSAS diagnosed
by polysomnography (apnea-hypopnea index [AHI] ⬎ 10 events
per hour) consecutively admitted to our Department of Pneumology over a 5-year period for the administration of nasal CPAP.
In these patients, LVEF was systematically measured using
radionuclide angiography as part of a routine evaluation.
Body weight was measured to the nearest 0.1 kg with subjects
in indoor clothing and no shoes. Height was measured to the
nearest 0.5 cm with a wall-mounted stadiometer, in the same
conditions. Body mass index (BMI) was calculated as weight
divided by height squared. Obesity was defined as a BMI ⬎ 30,
and massive obesity was defined as BMI ⬎ 40.
Diabetes mellitus was defined by a fasting blood glucose level
ⱖ 7.7 mmol/L, a postprandial blood glucose ⱖ 11 mmol/L, or a
history of regular treatment for previously known diabetes.
Systemic arterial hypertension was defined as systolic BP
ⱖ 160 mm Hg or diastolic BP ⱖ 95 mm Hg, observed over at
least three recordings. Patients with a history of regular antihypertensive medication for known systemic arterial hypertension
were also considered as hypertensive.
Exclusion Criteria
Exclusion criteria were as follows: (1) central sleep apnea,
defined as a central apnea index (AI) ⬎ 5/h associated with an
obstructive AI ⬍ 5/h; (2) unstable cardiorespiratory status, defined as the occurrence of respiratory failure, bronchopulmonary
infection, or congestive heart failure in the previous 2 months;
(3) coronary artery disease, defined as a typical angina pectoris, a
prior myocardial infarction, a positive exercise test result, positive
myocardial scintigraphy or positive coronary angiography findings; (4) valvulopathy, permanent atrial fibrillation, congenital
heart disease; and (5) chronic severe alcoholism.
Polysomnography
An overnight polygraphic sleep study was carried out in the
sleep laboratory using standard recording techniques with the
Alvar polygraphic recorder (Medical Equipment International;
Lyon, France) and Nightingale software (Deltamed; Paris,
France). Sleep was monitored with EEG, an electrooculogram,
and chin electromyogram. Air-flow recording, by means of an
oronasal thermistor-detected apnea, defined as cessation of air
flow for at least 10 s. The AI was calculated as the number of
apneas per hour of sleep. The type of apnea was defined by the
analysis of thoracoabdominal movements, which were recorded
by respiratory inductive plethysmography using a mercury strain
gauge (Volucapt; Vickers; Bordeaux, France). The transducers
were placed around the chest and abdomen.
Arterial oxyhemoglobin saturation (Sao2) was recorded by
means of a pulse oximeter (Oxyshuttle; SensorMedics; Yorba
Linda, CA). Hypopnea was defined as a decrease in ventilation
Myocardial Scintigraphy and Echocardiography
Myocardial scintigraphy and echocardiography were performed only in those patients in whom radionuclide angiography
showed LV systolic dysfunction. The aim of the myocardial
scintigraphy was to exclude a silent myocardial ischemia, related
to coronary artery disease. Echocardiography was undertaken to
exclude significant valvulopathy that could have been missed on
clinical examination, ECG, and chest radiography.
Single-photon emission CT myocardial study with a dipyridamole stress test was performed, using an IV infusion of dipyridamole, 0.6 mg/kg. An IV injection of 111 megabecquerel
thallous chloride Tl 201, or 296 to 740 megabecquerel 99mTclabelled methoxy-isobutyl-isonotrile (depending on the patient’s
weight) was followed by single-photon emission CT acquisition:
30 frames on a 180° arc extending from 45° right anterior oblique
to 45° left posterior oblique position (30 s per frame, matrix
64 ⫻ 64). Horizontal long-axis, short-axis, and vertical long-axis
slices were reconstructed using filtered backprojection. Myocardial segment activity was assessed on a short-axis sliced bull’s eye,
where the maximum count per pixel of each cut was normalized
to a value of 100%. A new acquisition using the same procedure
was performed following a rest injection, 240 min later for
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Clinical Investigations
thallium delayed imaging, 2 days later for methoxy-isobutylisonotrile rest imaging. Myocardial ischemia was defined as the
presence of a myocardial perfusion defect on the dipyridamole
images, which disappeared or markedly decreased on the rest
images. Doppler echocardiography was performed (Model
77020-CF; Hewlett-Packard; Andover, MA).
Statistical Analysis
The results are presented as mean (SD) values and as percentages. Quantitative data were compared in patients with LV
systolic dysfunction and in those with normal LV systolic function
using the Student t test, and the percentages were compared in
the two groups using the ␹2 test.
Results
The main characteristics of the patients are summarized in Table 1. The study population included
169 OSAS patients with a mean AHI of 47/h. The
AHI was ⬎ 30/h in 71% of the patients, and ⬎ 50/h
in 41%. Seventy-nine percent of the patients were
obese, with massive obesity in 37%.
Radionuclide angiography could be performed in
all patients without any technical failure. LV systolic
dysfunction was present in 7.7% (13 of 169 patients)
of the study population, and these patients had a
mean LVEF of 42 ⫾ 6%, while the mean LVEF was
63 ⫾ 6% in the 156 patients with normal LV systolic
function. The LVEF ranged from 40 to 50% in nine
patients, and from 30 to 40% in four patients. The
lowest LVEF value was 32%. The alteration in LV
function was diffuse in all these 13 patients, without
segmental akinesis or hypokinesis.
Myocardial scintigraphy with a dipyridamole stress
test was performed in the 13 patients with LV
systolic dysfunction and did not disclose a pattern of
myocardial ischemia in any of these patients. Doppler echocardiography was also performed in the 13
patients with LV systolic dysfunction, and was technically satisfactory in 10 of these patients. None of
these patients had significant valvulopathy or segmental
wall motion abnormalities of the left ventricle.
Table 1—Characteristics of the Study Population
(n ⴝ 169)*
Variables
Age, yr
Male/female gender, No.
Weight, kg
BMI
BMI ⬎ 30, %
BMI ⬎ 40, %
AHI, episodes/h
AHI ⬎ 30/h, %
AHI ⬎ 50/h, %
Hypertension, %
Diabetes mellitus, %
Discussion
This study showed that left ventricular systolic
dysfunction, diagnosed by radionuclide angiography,
Table 2—Polysomnographic Data in Patients With LV
Systolic Dysfunction vs Those With Normal LV
Systolic Function*
LVEF ⬍ 50% LVEF ⱖ 50%
(n ⫽ 13)
(n ⫽ 156)
p Value
Data
53 (12)
137/32
111.4 (32.8)
38 (10.4)
79
37
47 (23)
71
41
50
24
*Data are presented as mean (SD) unless otherwise indicated.
www.chestjournal.org
The polysomnographic data are shown in Table 2.
The AHI, the AI, and the parameters of nocturnal
oxyhemoglobin desaturation did not significantly differ between patients with LV systolic dysfunction
and those with normal LV function. Age, sex ratio,
body weight, BMI, and the percentages of patients
with obesity, hypertension, diabetes mellitus, or history of smoking did not significantly differ between
patients with LV systolic dysfunction and those with
normal LV function (Table 3). The percentages of
patients with a history of regular use of ␤-blockers,
angiotensin-converting enzyme (ACE) inhibitors, or
diltiazem did not significantly differ between the two
groups (Table 3).
LVEF was measured using radionuclide angiography following a reversal of OSAS in 7 of the 13
patients with LV systolic dysfunction. Six patients were
treated with nasal CPAP, and one patient underwent
uvulopalatopharyngoplasty. The mean delay between
the two measurements of LVEF was 12 ⫾ 5 months.
The LVEF increased significantly from 44 ⫾ 3% before treatment to 62 ⫾ 4% after treatment (Table 4).
All seven patients had normal LVEF (⬎ 50%) following treatment. The body weight did not significantly
vary between the two measurements of LVEF. Of
those seven patients, cardiac medications were used in
three patients with systemic hypertension, which had
been treated with a combination of ACE inhibitor and
diuretic for several years, but these medications remained unchanged during the follow-up period. In the
six other patients with LV dysfunction, a second LVEF
measurement was not performed because two patients
refused nasal CPAP therapy, two patients received
nasal CPAP ⬍ 3 h per night, and two patients were
unavailable for follow-up.
Variables
AHI, episodes/h
AI, episodes/h
Mean apnea duration, s
Minimal Sao2, %
TST with Sao2 ⬍ 90%, %
TST with Sao2 ⬍ 80%, %
Obstructive/all-type
apneas, %
Central/all-type apneas, %
Mixed/all-type apneas, %
54 (23)
43 (18)
23 (5)
57 (13)
72 (33)
38 (32)
70 (27)
47 (24)
37 (23)
23 (6)
64 (15)
64 (32)
24 (27)
77 (24)
NS
NS
NS
NS
NS
NS
NS
15 (14)
15 (20)
13 (15)
10 (15)
NS
NS
*Data are presented as mean (SD). NS ⫽ not significant.
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1135
Table 3—Anthropometric Data, Cardiovascular Risk
Factors, and Cardiac Medications in Patients With
LV Systolic Dysfunction vs Those with Normal LV
Systolic Function*
Variables
Age, yr
Male, %
Weight, kg
BMI
BMI ⬎ 30, %
Hypertension, %
Diabetes mellitus, %
Smoking, %
Cigarette pack-years
␤-Blockers, %
ACE inhibitors, %
Diltiazem, %
LVEF ⬍ 50%
(n ⫽ 13)
LVEF ⱖ 50%
(n ⫽ 156)
51 (11)
77
110.5 (35.5)
37.8 (10.6)
69
54
15
23
26 (24)
15
23
0
53 (12)
81
111.4 (32.7)
38 (10.4)
80
50
24
34
19 (22)
17
21
1
p Value
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
*Data are presented as mean (SD) unless otherwise indicated. See
Table 2 for expansion of abbreviation.
was observed in 7.7% (13 of 169 patients) with OSAS
requiring nasal CPAP, and with no associated cardiac
disease. LV function impairment was moderate, as
the lowest value of LVEF was 32%. In the seven
patients with LV dysfunction in whom a second
measurement of LVEF could be obtained following
efficient treatment of OSAS, LVEF improved significantly and reached normal values in all of them.
This LV systolic dysfunction was observed in a
study population in whom an associated cardiac
disease had been excluded. It has been demonstrated that OSAS patients have a high prevalence of
cardiovascular risk factors.16 A coexisting coronary
artery disease would be a major confounding factor
in the interpretation of LVEF measurements in
patients with OSAS. Therefore, the study population
did not include patients with a previously diagnosed
coronary artery disease. Moreover, in those patients
with OSAS with LV dysfunction, myocardial scintigraphy with dipyridamole stress test was systematically performed and did not reveal signs of myocardial ischemia. Segmental LV wall motion
disturbances were not demonstrated in any of these
Table 4 —Evaluation of LV Systolic Function Before
and After Treatment of OSAS With Nasal CPAP
(n ⴝ 6) or Pharyngoplasty (n ⴝ 1)*
Variables
Before Treatment
After Treatment
p Value†
LVEF, %
AHI, events/h
Weight, kg
44 (3)
62 (21)
117.4 (38.6)
62 (4)
10 (10)
112.9 (38.4)
⬍ 0.001
⬍ 0.001
NS
*Data are presented as mean (SD). See Table 2 for expansion of
abbreviation.
†Wilcoxon test.
patients by radionuclide angiography or echocardiography. Therefore, it is very unlikely that the LV
systolic dysfunction observed in our patients with
OSAS could be related to a silent coronary artery
disease. Valvulopathy and congenital heart disease
were excluded in these patients by echocardiography. Systemic hypertension was observed in 54% of
the patients with LV dysfunction and could theoretically have affected LV function. Unlike other authors,5,8 we did not exclude patients with systemic
hypertension, since it has been clearly demonstrated
that OSAS is a risk factor for daytime systemic
hypertension.10 –14 However, in our study, the prevalence of systemic hypertension did not significantly
differ between patients with and without LV dysfunction.
The prevalence of obesity was high (69%) in our
OSAS patients with LV dysfunction, and this might
be a confounding factor in assessing the effects of
OSAS on LV function, since obesity in itself is a
well-known cause of LV systolic dysfunction.17,18
Decreased LVEF in obese subjects is influenced,
among other factors, by the degree of obesity.19
Nevertheless, epidemiologic data have shown that
obesity is strongly associated with OSAS, so that the
majority of OSAS patients are usually obese.20,21 In
our study, the BMI was not significantly greater in
the patients with LV dysfunction when compared to
those with normal LV function. Thus, it is likely that
the daytime LV systolic dysfunction observed in our
OSAS patients was primarily related to nocturnal
apneas and hypopneas because it could not be
explained by an associated cardiac disease, a higher
prevalence or degree of obesity, or a higher prevalence of systemic hypertension. Nonetheless, these
results need to be confirmed by prospective studies
comparing LV function in OSAS patients and in
OSAS-free control subjects who should be matched
in terms of BMI, age, and gender.
The hypothesis of a direct link between OSAS and
daytime LV dysfunction is strengthened by the fact
that we observed normalization of LV systolic function following treatment of OSAS in all the seven
patients in whom a second determination of LVEF
was performed. In these patients, there was no
confounding factor during the follow-up period, such
as a decrease in body weight or a change in cardiac
medications that could modify LV function. Malone
and coworkers4 have shown, in eight patients with
severe OSAS and congestive heart failure secondary
to idiopathic dilated cardiomyopathy, that LVEF
increased significantly from 37 ⫾ 4% pretreatment
to 49 ⫾ 5% after 4 weeks of nasal CPAP therapy. In
28 patients with severe OSAS and no overt ischemic
heart disease, Krieger and coworkers22 reported a
significant increase in LVEF from 59 ⫾ 1% to
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Clinical Investigations
63 ⫾ 1% after 1 year of treatment with nasal CPAP,
but the interest of this study is limited by the fact
that only two patients had a pretherapeutic LVEF
⬍ 50%. A rise of ⬎ 10% in LVEF was documented
in 5 of 11 children with OSAS after adenotonsillectomy, of whom 3 children had a low LVEF before
surgery.23
Patients with OSAS have recurrent increases in
LV afterload during sleep that result from large
negative intrathoracic pressure swings, hypoxemia,
and arousals from sleep.24 In patients with OSAS and
congestive heart failure secondary to idiopathic dilated cardiomyopathy or coronary artery disease, the
nocturnal increase in LV afterload results primarily
from surges in systolic BP, with reductions in intrathoracic pressure playing a minor role.25 Apnearelated hypoxemia and arousals from sleep increase
sympathetic nervous system activity that results in
systemic vasoconstriction.26 Recurrent LV strain
over several hours of apnea may cumulatively lead to
chronic daytime LV dysfunction. Hypoxemia related
to apnea can also impair LV myocardial contractility.27 The improvement in LV systolic function following a reversal of OSAS by nasal CPAP is mainly
related to a reduction in nocturnal LV afterload,25
but may also be explained by a down-regulation of
sympathetic adrenergic activity and an improvement
in myocardial contractility.4 In our study, the patients with LV systolic dysfunction did not demonstrate more severe OSAS in terms of AHI or nocturnal Sao2, but one cannot exclude that these patients
actually had a more important increase in nocturnal
systemic BP and/or a higher sympathetic nervous
system activity. Unfortunately we did not perform
monitoring of nocturnal BP, nor measurements of
plasma or urinary noradrenaline concentrations.
LV systolic dysfunction is a rare complication of
OSAS as was observed in ⬍ 10% of the patients in
our study. Other types of LV involvement have been
described in patients with OSAS. Hedner and coworkers5 showed that LV hypertrophy is a common
phenomenon in OSAS patients without daytime
systemic hypertension. However, in a recent study,28
the increase in LV mass that was observed in OSAS
patients was found to be influenced by BMI, age,
and the presence of hypertension, but was not
correlated with the severity of OSAS. Alchanatis and
coworkers8 demonstrated that patients with severe
OSAS had LV diastolic dysfunction that improved
significantly following nasal CPAP therapy.
In conclusion, the results of this study suggest that
OSAS may be a direct cause of LV systolic dysfunction that can resolve following reversal of nocturnal
apneas. Further studies are needed to evaluate the
prevalence of LV systolic dysfunction in patients with
less severe OSAS, and to clarify the mechanisms
www.chestjournal.org
underlying the links between nocturnal apneas and
daytime LV systolic dysfunction.
References
1 Parker JD, Brooks D, Kozar LF, et al. Acute and chronic
effects of airway obstruction on canine left ventricular performance. Am J Respir Crit Care Med 1999; 160:1888 –1896
2 Levy PA, Guilleminault C, Fagret D, et al. Changes in left
ventricular ejection fraction during REM sleep and exercise
in chronic obstructive pulmonary disease and sleep apnoea
syndrome. Eur Respir J 1991; 4:347–352
3 Buda AJ, Schroeder JS, Guilleminault C. Abnormalities of
pulmonary artery wedge pressures in sleep-induced apnea.
Int J Cardiol 1981; 1:67–74
4 Malone S, Liu PP, Holloway R, et al. Obstructive sleep
apnoea in patients with dilated cardiomyopathy: effects of
continuous positive airway pressure. Lancet 1991; 338:1480 –
1484
5 Hedner J, Ejnell H, Caidhal K. Left ventricular hypertrophy
independent of hypertension in patients with obstructive
sleep apnoea. J Hypertens 1990; 8:941–946
6 Hanly P, Sasson Z, Zuberi N, et al. Ventricular function in
snorers and patients with obstructive sleep apnea. Chest
1992; 102:100 –105
7 Laaban JP, Cassuto D, Orvoen-Frija E, et al. Cardiorespiratory consequences of sleep apnoea syndrome in patients with
massive obesity. Eur Respir J 1998; 11:20 –27
8 Alchanatis M, Paradellis G, Pini H, et al. Left ventricular
function in patients with obstructive sleep apnoea syndrome
before and after treatment with nasal continuous positive
airway pressure. Respiration 2000; 67:367–371
9 Chuang ML, Danias PG, Riley MF, et al. Effect of increased
body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection
fraction, and mass. Am J Cardiol 2001; 87:71–74
10 Grote L, Ploch T, Heitmann J, et al. Sleep-related breathing
disorder is an independent risk factor for systemic hypertension. Am J Respir Crit Care Med 1999; 160:1875–1882
11 Peppard PE, Young T, Palta M, et al. Prospective study of the
association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342:1378 –1384
12 Bixler EO, Vgontzas AN, Lin HM, et al. Association of
hypertension and sleep-disordered breathing. Arch Intern
Med 2000; 160:2289 –2295
13 Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea
syndrome as a risk factor for hypertension: population study.
BMJ 2000; 320:479 – 482
14 Nieto FJ, Young TB, Lind BK, et al. Association of sleepdisordered breathing, sleep apnea, and hypertension in a
large community-based study. JAMA 2000; 283:1829 –1836
15 Weitzenblum E, Chaouat A, Kessler R, et al. Daytime
hypoventilation in obstructive sleep apnoea syndrome. Sleep
Med Rev 1999; 3:79 –93
16 Kiely JL, McNicholas WT. Cardiovascular risk factors in
patients with obstructive sleep apnoea syndrome. Eur Respir J
2000; 16:128–133
17 Alpert MA, Alexander JK, Chakko S. Obesity and ventricular
function in man: systolic function. In: Alpert MA, Alexander
JK, eds. The heart and lung in obesity. New York, NY: Futura
Publishing, 1998; 77–94
18 Alpert MA, Lambert CR, Terry BE, et al. Interrelationship of
left ventricular mass, systolic function and diastolic filling in
normotensive morbidly obese patients. Int J Obes 1995;
19:550 –557
19 Licata G, Scaglione R, Barbagallo M, et al. Effect of obesity
CHEST / 122 / 4 / OCTOBER, 2002
Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21983/ on 05/02/2017
1137
20
21
22
23
on left ventricular function studied by radionuclide angiocardiography. Int J Obes 1991; 15:295–302
Wittels EH, Thompson S. Obstructive sleep apnea and
obesity. Otolaryngol Clin North Am 1990; 23:751–760
Grunstein RR, Wilcox I. Sleep-disordered breathing and
obesity. Baillieres Clin Endocrinol Metab 1994; 8:601– 628
Krieger J, Grucker D, Sforza E, et al. Left ventricular ejection
fraction in obstructive sleep apnea: effects of long-term
treatment with nasal continuous positive airway pressure.
Chest 1991; 100:917–921
Tal A, Leiberman A, Margulis G, et al. Ventricular dysfunction in children with obstructive sleep apnea: radionuclide
assessment. Pediatr Pulmonol 1988; 4:139 –143
24 Naughton M. Heart failure and obstructive apnoea. Sleep
Med Rev 1998; 2:93–103
25 Tkacova R, Rankin F, Fitzgerald FS, et al. Effects of continuous positive airway pressure on obstructive sleep apnea and
left ventricular afterload in patients with heart failure. Circulation 1998; 98:2269 –2275
26 Fletcher EC. Sympathetic activity and blood pressure in the
sleep apnea syndrome. Respiration 1997; 64(suppl 1):22–28
27 Allen DG, Orchard CH. Myocardial contractile function
during ischemia and hypoxia. Circ Res 1987; 60:153–168
28 Niroumand M, Kuperstein R, Sasson Z, et al. Impact of
obstructive sleep apnea on left ventricular mass and diastolic function. Am J Respir Crit Care Med 2001; 163:
1632–1636
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