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998
Thorax 1995;50:998-1004
Sleep-related breathing disorders * 4
Series editor: P M A Calverley
Consequences of sleep disordered breathing
Kathleen A Ferguson, John A Fleetham
values.2 Blood pressure fluctuates considerably
during REM sleep and is on average 5% higher
than the preceding non-REM sleep.3 In patients
with sleep disordered breathing there are brief
phasic changes in blood pressure superimposed
on a cyclical pattern which coincide with the
upper airways obstruction (fig 2).4 The brief
phasic changes in blood pressure are secondary
to the large changes in intrathoracic pressure
during obstructed respiration. Systemic blood
pressure may increase by up to 20% during
OSA and is maximal immediately after apnoea
termination.56 The mechanism of the cyclical
pattern in blood pressure during sleep disordered breathing is probably multifactorial
in origin. Hypoxaemia, hypercapnic acidosis,
increased respiratory effort, and the increased
sympathetic activity associated with the
awakening7 have all been proposed as mechanisms. Hypoxaemia does not appear to be a
major causative factor as blood pressure remains unchanged in patients with OSA during
Cardiac consequences
SYSTEMIC HYPERTENSION
supplemental oxygen therapy.8 Sympathetic
Systemic blood pressure normally decreases nervous output and catecholamine production
by 5-14% in non-rapid eye movement (non- are both increased during OSA.9 In patients
REM) sleep compared with awake resting with OSA, catecholamine secretion decreases
Sleep disordered breathing is common and may
affect up to 24% of men and 9% of women.'
There is a continuum in sleep disordered
breathing associated with progressively more
clinical consequences, from chronic snoring to
obstructive sleep hypopnea to severe obstructive sleep apnoea (OSA). Although certain
manifestations of sleep disordered breathing
have been described for many years, a wider
recognition of the clinical consequences has
only occurred in the last decade. Sleep disordered breathing is characterised by recurrent
upper airways obstruction which results in episodic asphyxia and interruption of the normal
sleep pattern. The clinical consequences of
sleep disordered breathing are quite diverse
and are usually caused by either the recurrent
asphyxia or sleep fragmentation (fig 1).
Respiratory Division,
Department of
Medicine,
Vancouver Hospital
and Health Science
Centre (UBC
Pavilion),
2211 Wesbrook Mall,
Vancouver,
British Columbia,
Canada V6T 2BS
K A Ferguson
J A Fleetham
Reprint requests to:
Dr J A Fleetham.
Figure 1 Pathogenesis of the consequences of sleep disordered breathing.
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Consequences of sleep disordered breathing
following effective treatment with either tracheostomy'0 or nasal CPAP therapy."
Systemic hypertension occurs in 40-60%
patients with OSA'2 and its severity is related
to apnoea severity.'3 In contradistinction to
normal subjects, blood pressure is higher in the
moming than in the evening in patients with
OSA.'4 Several studies have also shown that
22-30% of patients with systemic hypertension
also have OSA.'"'7 These observations have
led many to assume that the daytime systemic
hypertension present in patients with sleep disordered breathing is due to the recurrent blood
pressure increases during sleep. Most of the
previous epidemiological studies did not, however, control for other confounding causes of
hypertension. Obesity,""2' age, 1920 and alcohol
consumption 'have subsequently been shown
to be the major factors associated with systemic
hypertension in patients with OSA, with apnoea
severity a very much less important factor.'822
There is, however, some evidence for a causal
association between OSA and systemic hypertension from studies in patients effectively
treated with modalities other than weight loss.
Nasal continuous positive airway pressure
(CPAP) therapy acutely prevents the cyclical
pattern of blood pressure changes during
OSA.23 Long term treatment of OSA with tracheostomy24 and nasal CPAP25-27 reduces systemic blood pressure independently of any
weight changes.
The association between sleep disordered
breathing and systemic hypertension appears
to be mainly due to similar risk factors for
both conditions. It is important to consider
the diagnosis of sleep disordered breathing in
patients with systemic hypertension, but further
diagnostic studies are not indicated in the absence of other features of sleep disordered
breathing. Systemic hypertension should be
treated in patients with sleep disordered breathing, but there are no current data to recommend
a specific antihypertensive approach in these
patients.
monary hypertension. Pulmonary artery pressure decreased in six patients with severe OSA
following tracheostomy.3' A larger study found
no significant decrease in pulmonary artery
pressure following chronic nasal CPAP therapy.32 However, many of these patients had
mild OSA and there was a decrease in pulmonary artery pressure in those patients with
pulmonary hypertension. Right heart failure
and hypercapnic respiratory failure both occur
in severe OSA. These patients tend to be more
obese, with daytime hypoxaemia and associated
airways obstruction.3336 Chronic alcohol consumption has also been reported to be more
common in these patients.37
The presence ofpulmonary hypertension and
associated right heart failure in patients with
sleep disordered breathing is invariably indicative of severe disease which requires
prompt diagnosis and treatment. It is important
to consider the diagnosis of sleep disordered
breathing in patients with unexplained pulmonary hypertension. However, further diagnostic studies are not indicated in the absence
of other features of sleep disordered breathing.
CARDIAC FUNCTION
Cardiac output decreases during OSA due to
a decrease in heart rate without a concomitant
increase in stroke volume5 caused by a decreased left ventricular preload.38 Left ventricular afterload increases during OSA and it
has been hypothesised that this would result
in left ventricular hypertrophy or dysfunction.
There are several reports of echocardiography
in patients with OSA. Hedner and associates39
excluded patients with systemic hypertension
and found a larger left ventricular mass in
patients with OSA compared with control subjects. However, in a better controlled study
Hanly and colleagues40 failed to show any
difference in left ventricular size or function
between snorers and patients with OSA. Treatment of sleep disordered breathing can improve
cardiac function in selected patients.
PULMONARY HYPERTENSION/RIGHT HEART
FAILURE
Pulmonary artery pressures usually remain relatively unchanged during sleep in normal sub- EKG
jects.28 In contrast, pulmonary artery pressure Thermistor
i,
increases by up to 100% during REM sleep.6 Rib cage
ij
I
".'jU1Vi4,.
The cyclical changes in pulmonary artery pressure parallel the changes in systemic blood
pressure (fig 2). These changes are due both Abdomen
"
'
to the effects of obstructed inspiratory efforts
on pulmonary and cardiac dynamics, and to PRA
20
0I.i -tr )\;
(mm Hg) -20
pulmonary hypoxic vasoconstriction.
_40
Pulmonary hypertension occurs in a sub60
40
stantial proportion of patients with sleep dis- PPA
ordered breathing. The prevalence of (mm Hg)
0,Y%
pulmonary hypertension in patients with OSA
has been reported to be between 10% and
100
90
20%,29 but may be as high as 55% in moderate Sao2
80
(%)
70
60 s
to severe disease.30 Many studies of pulmonary
90
hypertension in sleep disordered breathing have Svo2
70
(%)
50
excluded patients with chronic obstructive lung
disease, though frequently these two diseases Figure 2 Changes in pulmonary artery (PPA) and right
coexist. Several studies have evaluated the atrial (PRA) pressures during obstructive sleep apnoea.
effect of long term treatment of OSA on pul- Reproduced from ref 108 with permission.
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Ferguson, Fleetham
Long term nasal CPAP therapy has been
shown to result in a small increase in left
ventricular ejection fraction in patients with
OSA and normal cardiac function.4' Nasal
CPAP therapy results in a significant increase
in cardiac function in patients with a cardiomyopathy and associated OSA.42 Extrapolating from these data, nasal CPAP has
been proposed as an adjunct therapy for nonOSA patients with congestive heart failure and
Cheyne-Stokes respiration.43 Other reports4445
have failed to confirm any improvement in
cardiac function and have found that many of
these patients are unable to tolerate nasal CPAP
therapy. Until definitive studies in this field
are completed, the long term efficacy of nasal
CPAP treatment on cardiac function in patients
without OSA needs to be evaluated on an
individual basis.
intracranial pressure increases in a cyclical pattern in patients with OSA. This cyclical increase
in intracranial pressure coincides with the
OSA and is maximal immediately after apnoea
termination.57 The increase in intracranial pressure is secondary to both the cerebral vasodilatation caused by hypercapnea and the
apnoea related increases in systemic blood pressure and central venous pressure. The increased intracranial pressure is probably the
major contributing cause of the nocturnal and
morning headaches present in some patients
with sleep disordered breathing. The increased
intracranial pressure also results in raised intraocular pressure which may result in glaucoma
which can be a rare clinical presentation of
sleep disordered breathing.58 It is important to
consider sleep disordered breathing in patients
with nocturnal headaches or glaucoma which
is refractory to treatment.
Patients with sleep disordered breathing have
ISCHAEMIC HEART DISEASE
an increased cerebrovascular mortality and
Sleep disordered breathing has been shown to morbidity,59 and 53% of male patients with a
be a significant risk factor in the development cerebrovascular accident (CVA) were chronic
of ischaemic heart disease.4647 The combined snorers'o in one report. Of these, 35% had their
effects of systemic hypertension, hypoxaemia, CVA during sleep and snoring was the only
and increased sympathetic activity during sleep factor which correlated with the diurnal variare thought to promote the development of ation in the time of CVA. Furthermore, in a
atherosclerosis. ST depression is relatively case controlled study of 400 patients admitted
common in patients with OSA during overnight to hospital with a CVA, snoring has been shown
ECG monitoring, and the duration of this is to be both an important risk factor for the
reduced by nasal CPAP therapy.48 This ST development of a CVA and to adversely affect
depression may reflect myocardial ischaemia prognosis."
or non-specific changes associated with OSA.
Myocardial ischaemia is reported to have occurred during polysomnography in five of 20 EXCESSIVE DAYTIME SLEEPINESS
patients with combined ischaemic heart disease Sleep disordered breathing frequently presents
and OSA.49
with excessive daytime sleepiness which can
be evaluated both subjectively and objectively.
The Epworth Sleepiness Scale is a quesCARDIAC ARRHYTHMIA
tionnaire which asks about the likelihood of
Cardiac rate normally decreases by 5-10% dur- falling asleep in eight different situations.62
ing non-REM sleep, with a slight increase dur- Patients with OSA tend to have a higher score
ing REM sleep.23 In patients with sleep which is related to apnoea severity and imdisordered breathing the vagal stimulation proves following nasal CPAP therapy. Excessive
caused by inspiring against the upper airway daytime sleepiness can also be objectively conobstruction results in sinus bradycardia during firmed by multiple sleep latency testing
the apnoea followed by a reflex tachycardia at (MSLT).6' Mean sleep latency is reduced in
apnoea termination.50 The degree of brady- patients with OSA, but may not improve in
cardia is related to the severity of the associated patients who say they are using the treatment.64
arterial oxygen desaturation5' and is blunted The maintenance of wakefulness test (MWT)
by administration of both atropine and sup- involves asking the patient to stay awake for 40
plemental oxygen.52 Cardiac arrhythmias dur- minutes on four occasions during the daytime.
ing sleep are present in up to 50% of patients Patients with OSA have a decreased ability to
with OSA.5' These arrhythmias are more fre- stay awake which is related to both apnoea
quent when the OSA is associated with arterial severity and arterial oxygen desaturation.65 In
oxygen desaturation54 and resolve following general, there is no need to perform an MSLT
effective treatment of the OSA.5' The cyclical or MWT in patients with sleep disordered
changes in heart rate seen in patients with sleep breathing unless their daytime sleepiness fails
disordered breathing can be confused with sick to improve with effective treatment.
sinus syndrome resulting in inappropriate treatSleep fragmentation, lack of slow wave sleep,
and recurrent hypoxaemia have all been proment with cardiac pacing.
posed as the cause of the excessive daytime
sleepiness present in sleep disordered breathing. It is a common clinical observation that
Neurological consequences
some patients with loud snoring and no OSA
CEREBROVASCULAR DISEASE
Cerebral blood flow and intracranial pressure may have excessive daytime sleepiness, whereas
both decrease during non-REM sleep and in- some patients with severe OSA deny any sleepicrease in REM sleep in normal subjects.55 How- ness.66 Bedard and associates demonstrated a
ever, cerebral blood flow decreases56 whilst relationship between the severity of sleep hyp-
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Consequences of sleep disordered breathing
oxaemia and objective tests of both sleepiness
and alertness in patients with moderate to
severe OSA.67 Apnoea severity was related to
objective tests of alertness, but not to sleepiness. Subsequently, Guilleminault and colleagues have shown that patients with OSA
and excessive daytime sleepiness have both
more sleep fragmentation and higher apnoea/
hypopnoea indices.68 Sleep disruption and recurrent hypoxaemia appear to interact to cause
the excessive daytime sleepiness present in
patients with sleep disordered breathing.
Excessive daytime sleepiness is a well recognised cause of both automobile and industrial accidents.69 Patients with untreated
OSA are poor drivers and have 2-3 times more
automobile accidents than other drivers.7>72
This poor driving has been confirmed with
driving simulators and improves with effective
treatment with nasal CPAP.7' Automobile accidents involving patients with OSA may result
in serious injury or death.74 It is important
to consider the diagnosis of sleep disordered
breathing when examining patients who fall
asleep while driving or at work. Patients with
sleep disordered breathing should be warned
about the risks of driving, whilst seriously impaired drivers with sleep disordered breathing
should be kept from driving until the sleep
disordered breathing is effectively treated.
Every physician involved in the management of
patients with sleep disordered breathing should
know and follow the local regulations for
notifying licensing authorities about impaired
drivers.75
1001
sleep disordered breathing in patients with Alzheimer's disease,87 whereas others have shown
more sleep disordered breathing in patients
with multi-infarct and Alzheimer's dementia.88
Currently there is no justification to screen
elderly or demented patients for sleep disordered breathing, but it is important to consider this diagnosis in any patient with
associated symptoms consistent with sleep disordered breathing.
Endocrine consequences
Decreased libido and/or impotence are frequently associated with sleep disordered
breathing. Of 50 patients with severe OSA,
44% were reported to have either diminished
sexual interest or performance."2 This sexual
dysfunction is probably related in part to the
daytime sleepiness or depression associated
with sleep disordered breathing. There are,
however, two reports8990 which suggest that
sleep disordered breathing causes hypothalamic-pituitary dysfunction which is reversible following effective treatment. This
reversible neuroendocrine dysfunction may
contribute to the decreased libido and impotence in patients with sleep disordered
breathing.
Haematological consequences
Secondary polycythaemia may occur in patients
with sleep disordered breathing although this
is uncommon in the absence of associated lung
disease. Serum erythropoietin concentrations
are not increased in patients with OSA or
Psychological/psychiatric consequences
related
to the degree of nocturnal hypIntellectual deterioration, personality, and be- oxaemia.9 However, the normal diurnal rehavioural changes are well recognised features duction in serum erythropoietin concentrations
of sleep disordered breathing. There are also during sleep does not occur in patients with
significant psychological consequences of sleep OSA, and this may be sufficient to cause secdisordered breathing related to interpersonal ondary polycythaemia.92 Nasal CPAP therapy
relationships at work and at home. Psycho- does reduce haematocrit acutely,9" but this is
logical testing in patients with sleep disordered probably more related to changes in intrabreathing has demonstrated significant deficits vascular volume than erythropoietin conin thinking, perception, memory, and the ability centrations. The degree of hypoxaemia in
to learn.76 Cognitive impairment is related to
with sleep disordered breathing may
the severity ofthe sleep hypoxaemia77 and sleep patients
not be sufficient to stimulate erythropoietin
fragmentation.78 Treatment of sleep disordered production and cause polycythaemia unless asbreathing may improve psychological status sociated with daytime hypoxaemia due to coand result in less anxiety and depression.79
disease.
Sleep disturbances are a common feature existing lung
of psychiatric disease, usually presenting as
disorders of initiating and maintaining sleep.
Sleep disordered breathing can also present Nephrological consequences
with psychiatric disease such as depression80 Patients with sleep disordered breathing comand psychosis8' which then improve with monly complain of nocturia which then imeffective treatment.82 Sleep disordered breath- proves with effective treatment.24 Atrial
ing may coexist with psychiatric illness, and natriuretic peptide concentrations are inrecognition ofthis will lead to appropnate treat- creased during sleep in patients with sleep disment.
ordered breathing94 and decrease with nasal
Sleep disordered breathing is more common CPAP therapy.95-97 The frequent nocturia in
in the elderly, but the impact of this on daytime patients with sleep disordered breathing is
function is unclear. Apnoea/hypopnoea severity probably related to diuresis and natriuresis
in the elderly does not appear to be related caused by the recurrent hypoxaemia.9899
to daytime neuropsychological dysfunction.83-85 Patients with sleep disordered breathing are
Similarly, the relationship between sleep dis- also more prone to have proteinuria which
ordered breathing and dementia is con- improves with effective treatment.100101 The
troversial.86 Some studies find no increase in mechanism of this proteinuria is unclear.
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Ferguson, Fleetham
1002
KAF was a Glaxo/Canadian Medical Research Council Fellow.
This study was supported by the British Columbia Health
Research Foundation.
1-0!
1 Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr
S. N Englj Med 1993;328:1230-5.
2 Khatri IM, Freis ED. Hemodynamic changes during sleep.
J Appl Physiol 1967;22:867-73.
3 Snyder F, Hobson JA, Morrison DF, Goldfrank F. Changes
in respiration, heart rate, and systolic blood pressure in
human sleep. J Appl Physiol 1964;19:417-22.
4 Mateika JH, Matieka S, Slutsky AS, Hoffstein V. The effect
of snoring on mean arterial blood pressure during nonREM sleep. Am Rev Respir Dis 1992;145:131-46.
5 Stoohs R, Guilleminault C. Cardiovascular changes associated with obstructive sleep apnea syndrome. J Appl
r
0.9
0.1
2 0-8
E 0.6
0
1
2
3
6
5
4
Interval (years)
7
8
9
Figure 3 Probability of cumulative survival for patients with obstructive sleep apnoea
who were either untreated (A, n=244) or treated with uvulopalatophatyngoplasty
(, n= 149) or nasal CPAP (E) n = 126). Reproduced from ref 105 with permission.
Physiwl 1992;72:583-9.
6 Coccagna G, Mantovani M, Brignani F, Parchi C, Lugaresi
E. Continuous recording of the pulmonary and systemic
arterial pressure during sleep in syndromes of hypersomnia with periodic breathing. Bull Eur Physiopathol
Respir 1972;8:1159-72.
7 Hedner JA, Wilcox I, Laks L, Grunstein RR, Sullivan CE.
A specific and potent pressor effect of hypoxia in patients
with sleep apnea. Am Rev Respir Dis 1992;146:1240-5.
8 Ringler J, Basner RC, Shannon R, Schwartzstein R, Manning H, Weinberger SE, et al. Hypoxemia alone does not
explain blood pressure elevations after obstructive apneas.
J Appl Physiol 1990;69:2143-8.
9 Marrone 0, Riccobone L, Salvaggio A, Mirabella A,
Bonanno A, Bonsignore MR. Catecholamines and blood
pressure in obstructive sleep apnea syndrome. Chest 1993;
103:722-7.
10 Fletcher EC, Miller J, Schaaf JW, Fletcher JG. Urinary
catecholamines before and after tracheostomy in patients
with obstructive sleep apnea and hypertension. Sleep
1987;10:35-44.
Mortality
There are limited retrospective data on the
mortality asociated with sleep disordered
breathing, but most studies suggest a decreased
long term survival. Partinen and colleagues'02
reported decreased five year survival in patients
with untreated OSA compared with both
patients treated by tracheostomy and the US
age adjusted survival curve. He and coworkersl03 demonstrated a decreased survival
in patients with untreated OSA with an apnoea
index of >20/hour. This difference was most
evident in patients below 50 years of age. The
major cause of increased mortality in sleep
disordered breathing appears to be cardiovascular in nature.104 There is no difference in
the long term survival of patients with OSA
treated with either corrective upper airway surgery or nasal CPAP (fig 3). 105 In elderly patients
the effect of sleep disordered breathing on long
term survival is less clear. Ancoli-Israel and
colleagues106 showed an association between
OSA and decreased survival in elderly women
but not in men. Bliwise and coworkers107 demonstrated no difference in mortality in a group
of treated and untreated elderly patients with
OSA compared with control subjects.
Conclusions
Sleep disordered breathing causes episodic asphyxia and sleep fragmentation which result in
many protean multisystem consequences. The
immediate consequences of sleep disordered
breathing have been extensively studied, but
the long term significance of these consequences has not been well established. This
would require long term prospective controlled
studies in matched groups of treated and untreated patients with sleep disordered breathing. Such studies are no longer feasible because
the currently available effective treatments
could not ethically be withheld for prolonged
periods of time.
11 Jennum P, Wildschi0dtz, Christensen NJ, Schwartz T.
Blood pressure, catecholamines, and pancreatic polypeptide in obstructive sleep apnea with and without nasal
continuous positive airway pressure (nCPAP) treatment.
Am J Hypertens 1989;2:847-52.
12 Guilleminault C, Tilkian A, Dement WC. The sleep apnea
syndromes. Ann Rev Med 1976;27:465-84.
13 Lavie P, Yoffe N, Berger I, Peled R. The relationship
between the severity of sleep apnea syndrome and 24-h
blood pressure values in patients with obstructive sleep
apnea. Chest 1993;103:717-21.
14 Hoffstein V, MateikaJ. Evening-to-morning blood pressure
variations in snoring patients with and without obstructive
sleep apnea. Chest 1992;101:379-84.
15 Kales A, Bixler EO, Cadieux RJ, Schneck DW, Shaw LC
III, Locke TW, et al. Sleep apnoea in a hypertensive
population. Lancet 1984;ii:1005-8.
16 Lavie P, Ben-YosefR, RubinAE. Prevalence of sleep apnea
syndrome among patients with essential hypertension.
Am HeartJ 1984;108:373-6.
17 Fletcher EC, DeBehnke RD, Lovoi MS, Gorin AB. Undiagnosed sleep apnea in patients with essential hypertension. Ann Intern Med 1985;103:190-5.
18 Hoffstein V, Rubinstein I, Mateika S, Slutsky AS. Determinants of blood pressure in snorers. Lancet 1988;ii:
992-4.
19 Rauscher H, Popp W, Zwick H. Systemic hypertension in
snorers with and without sleep apnea. Chest 1992;102:
367-71.
20 Milhman RP, Redline S, Carlisle CC. Assaf AR, Levinson
PD. Daytime hypertension in obstructive sleep apnea prevalence and contributing risk factors. Chest 1991;99:
861-6.
21 StradlingJR, CrosbyJH. Relation between systemic hypertension and sleep hypoxaemia or snoring: analysis in 748
men drawn from general practice. BMJ' 1990;300:75-8.
22 Kiselak J, Clark M, Pera V, Rosenberg C, Redline S. The
association between hypertension and sleep apnea in
obese patients. Chest 1993;104:775-80.
23 Ali JN, Davies RJO, Fleetham JA, Stradling JR. The acute
effects of continuous positive airway pressure and oxygen
administration on blood pressure during obstructive sleep
apnea. Chest 1992;101:1526-32.
24 Guilleminault C, Simmons FB, Motta J, Cummiskey J,
Rosekind M, Schroeder JS, et al. Obstructive sleep apnea
syndrome and tracheostomy - long-term follow-up experience. Arch Intern Med 1981;141:985-8.
25 Suzuki M, Otsuka K, Guilleminault C. Long-term nasal
continuous positive airway pressure administration can
normalize hypertension in obstructive sleep apnea
patients. Sleep 1993;16:545-9.
26 Wilcox I, Grunstein RR, Hedner JA, Doyle J, Collins FL,
Fletcher PJ, et al. Effect of nasal continuous positve
airway pressure during sleep on 24-hour blood pressure
in obstructive sleep apnea. Sleep 1993;16:539-44.
27 Mayer J, Becker H, Brandenburg U, Penzel T, Peter JH,
Wichert Pv. Blood pressure and sleep apnea: Results
of long-term nasal continuous positive airway pressure
therapy. Cardiology 1991;79:84-92.
28 Lugaresi E, Coccagna G, Mantovani M, Lebrun R. Some
during drowsiness and sleep
periodic phenomena arising
Clin Neurophysiol 1972;32:701in man.
5.
29 Weitzenblum E, Krieger J, Apprill M, Vallee E, Ehrhart
M, Ratomaharo J, et aL Daytime pulmonary hypertension
in patients with obstructive sleep apnea. Am Rev Respir
Dis 1988;138:345-9.
Elctoencephalogr
Downloaded from http://thorax.bmj.com/ on May 2, 2017 - Published by group.bmj.com
1003
Consequences of sleep disordered breathing
30 Schroeder JS, Motta J, Guilleminault C. Hemodynamic
studies in sleep apnea. In: Guilleminault C, Dement WC,
eds. Sleep apnea syndromes. New York: Alan Liss, 1978:
177-99.
31 Motta J. Guilleminault C, Schroeder JS, Dement WC.
Tracheostomy and hemodynamic changes in sleep-induced apnea. Ann Intern Med 1978;89:454-8.
32 Sforza E, KreigerJ, Weitzenblum E, Apprill M, Lampert E,
Ratamaharo J, Long-term effects of treatment with nasal
continuous positive airway pressure on daytime lung function and pulmonary hemodynamics in patients with obstructive sleep apnea. Am Rev RespirDis 1990; 141:866-70.
33 Krieger J, Sforza E, Apprill M, Lampert E, Weitzenblum
E, Ratomaharo J. Pulmonary hypertension, hypoxemia,
and hypercapnia in obstructive sleep apnea patients. Chest
1989;96:729-37.
34 BradleyTD, Rutherford R, Lue F, Moldofsky H, Grossman
RF, Zamel N, et al. Role of diffuse airway obstruction in
the hypercapnia of obstructive sleep apnea. Am Rev Respir
Dis 1986-134:920-4.
35 Leech JA, Onal E, Baer P, Lopata M. Determinants of
hypercapnia in occlusive sleep apnea syndrome. Chest
1987;92:807-13.
36 Bradley TD, Rutherford R, Grossman RF, Lue F, Zamel
N, Moldofsky H. Role of daytime hypoxemia in the
pathogenesis of right heart failure in the obstructive sleep
apnea syndrome. Am Rev Respir Dis 1985;131:835-9.
37 Chan CS, Grunstein RR, Bye PTP, Woolcock AJ, Sullivan
CE. Obstructive sleep apnea with severe chronic airflow
limitation. Am Rev Respir Dis 1989;140:1274-8.
38 Tolle FA, Judy WV, Yu P-L, Marka ON. Reduced stroke
volume related to pleural pressure in obstructive sleep
apnea. J Appl Physiol 1983;55:1718-24.
39 HednerJ, Ejnell H, Caidahl K. Left ventricular hypertrophy
independent of hypertension in patients with obstructive
sleep apnoea. J Hypertens 1990;8:941-6.
40 Hanly P. Sasson Z, Zubeeri N, Alderson M. Ventricular
function in snorers and patients with obstructive sleep
apnea. Chest 1992:102:100-5.
41 KriegerJ, Grucker D, Sforza E, Chambron J, Kurtz D. Left
ventricular ejection fraction in obstructive sleep apnea:
effects of long-term treatment with nasal continuous
positive airway pressure. Chest 1991;100:917-21.
42 Malone S. Liu PP, Holloway R, Rutherford R, Xie A,
Bradley TD. Obstructive sleep apnoea in patients with
dilated cardiomyopathy: effects of continuous positive
airway pressure. Lancet 1991;338:1480-4.
43 Bradley TD, Holloway RM, McLaughlin PR, Ross BL,
Walters J, Liu PP. Cardiac output response to continuous
positive airway pressure in congestive heart failure. Am
Rev Respir Dis 1992;145:377-82.
44 Buckle P, Millar T, Kryger M. The effect of short-term
nasal CPAP on Cheyne-Stokes respiration in congestive
heart failure. Chest 1992;102:31-5.
45 Davies RJO, Harrington KJ, Ormerod OJM, Stradling JR.
Nasal continuous positive airway pressure in chronic heart
failure with sleep-disordered breathing. Am Rev Respir
Dis 1993;147:630-4.
46 Kosenvuo M, Kaprio J, Telakivi T, Partinen M, Heikkila
K, Sarna S. Snoring as a risk factor for ischaemic heart
disease and stroke in men. BMJ 1987;294:16-9.
47 Hung J, Whitford EG, Parsons RE, Hillman DR. Association of sleep apnoea with myocardial infarction in
men. Lancet 1990;336:261-4.
48 Hanly P, Sasson Z, Zuberi N, Lunn K. ST-segment depression during sleep in obstructive sleep apnea. Am 7
Cardiol 1993;71:1341-5.
49 Koehler U, Duibler H, Glaremin T, Junkermann H,
Lubbers C, Ploch T, et alNocturnal myocardial ischemia
and cardiac arrhythmia in patients with sleep apnea with
and without coronary heart disease. Klin Wochenschr 1991;
69:474-82.
50 Guilleminault C, Connolly S, Winkle R, Melvin K, Tilkian
A. Cyclical variation of the heart rate in sleep apnea
syndrome. Lancet 1984;i: 126-31.
51 Hanly PJ, George CF, Millar TW, Kryger MH. Heart rate
response to breath-hold, Valsalva and Mueller maneuvers
in obstructive sleep apnea. Chest 1989;95:735-9.
52 Zwillich C, Devlin T, White D, Douglas N, Weil J, Martin
R. Bradycardia during sleep apnea. J Clin Invest 1982;
69:1286-92.
53 Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and conduction disturbances during sleep in 400
patients with sleep apnea syndromne. Am J Cardiol 1983;
52:490-4.
54 Shepard J W, Garrison MW, Grither DA, Dolan GF.
Relationship of ventricular ectopy of oxyhemoglobin desaturation in patients with obstructive sleep apnea. Chest
1985;88:335-40.
55 Munari C, Calbucci F. Correlations between intracranial
pressure and EEG during coma and sleep. Electroencephalogr Clin Neurophysiol 1981;51:170-6.
56 Fischer AQ, Chaudary BA, Taormina MA, Akhtar B.
Intracranial hemodynamics in sleep apnea. Chest 1992;
102:1402-6.
57 Jennum P, Borgesen SE. Intracranial pressure and obstructive sleep apnea. Chest 1989;95:279-83.
58 Walsh JT, Montplaisir J. Familial glaucoma with sleep
apnoea: a new syndrome? Thorax 1982;37:845-9.
59 Smime S, Palazzi S, Zucconi M, Chierchia S, FeriniStrambi L. Habitual snoring as a risk factor for acute
vascular disease. Eur Respir J 1993;6: 1357-61.
60 Palomaki H, Partinen M, Juvela S, Kaste M. Snoring as
a risk factor for sleep-related brain infarction. Stroke 1989;
20:1311-5.
61 Spriggs DA, French JM, Murdy JM, Curless RH, Bates
D, James OFW. Snoring increases the risk of stroke
and adversely affects prognosis. Q J Med 1992;303:
555-62.
62 Johns MW. Reliability and factor analysis of the Epworth
sleepiness scale. Sleep 1992;15:376-81.
63 The clinical use of the multiple sleep latency test. Report
from the American Sleep Disorders Association. Sleep
1992;15:268-76.
64 Sangal RB, Thomas L, Mitler MM. Disorders of excessive
sleepiness - treatment improves ability to stay awake
but does not reduce sleepiness. Chest 1992;102:699-703.
65 Poceta JS, Timms RM, Jeong DU, Swui-ling H, Erman
MK, Mitler MM. Maintenance of wakefulness test in
obstructive sleep apnea syndrome. Chest 1992;101:
893-7.
66 Guilleminault C, Stoohs R, Clerk A, Cetel M, Maistros
P. A cause of excessive daytime sleepiness: The upper
airway resistance syndrome. Chest 1993;104:781-7.
67 Bedard MA, Montplaisir J, Richer F, Malo J. Nocturnal
hypoxemia as a determinant of vigilance impairment in
sleep apnea syndrome. Chest 1991;100:367-70.
68 Guilleminault C, Partinen M, Quera-Salva MA, Hayes B,
Dement WC, Nino-Murcia G. Determinants of daytime
sleepiness in obstructive sleep apnea. Chest 1988;94:32-7.
69 Mitler MM, Carskadon MA, Czeisler CA, Dement WC,
Dinges DF, Graeber RC. Catastrophes, sleep and public
policy: consensus report. Sleep 1988;11:100-9.
70 Findley LF, Unverzagt ME, Suratt PM. Automobile accidents involving patients with obstructive sleep apnea.
Am Rev Respir Dis 1988;138:337-40.
71 Aldrich MS. Automobile accidents in patients with sleep
disorders. Sleep 1989;6:487-94.
72 Haraldsson PO, Carenfelt C, Diderichsen F. Nygren A,
Tingvall C. Clinical symptoms of sleep apnea syndrome
and automobile accidents. ORL 1990;52:57-62.
73 Findley U, Fabrizio MJ, Knight H, Norcross BB, Laforte
AJ, Suratt PM. et al. Driving simulator performance in
patients with sleep apnea. Am Rev Respir Dis 1989;140:
529-30.
74 Findley U, Weiss JW, Jabour ER. Drivers with untreated
sleep apnea. A cause of death and serious injury. Arch
Intern Med 1991;151:1451-2.
75 Stradling JR. Obstructive sleep apnoea and driving. BMJ
1989;298:904-5.
76 Kales A, Caldwell AB, Cadieux RJ, Vela-Bueno A, Ruch
LG, Mayes SD. Severe obstructive sleep apnea - II:
Associated psychopathology and psychosocial consequences. J Chron Dis 1985;38:427-34.
77 Findley U, Barth JT, Powers DC, Wihoit SC, Boyd DG,
Suratt P. Cognitive impairment in patients with obstructive sleep apnea and associated hypoxemia. Chest
1986;90:686-90.
78 Cheshire K, Engleman H, Deary I, Shapiro C, Douglas
NJ. Factors impairing daytime performance in patients
with sleep apnea/hypopnea syndrome. Arch Intern Med
1992;152:538-41.
79 Klonoff H, Fleetham J, Taylor DR, Clark C. Treatment
outcome of obstructive sleep apnea - physiological and
neuro-psychological concomitants. JNerv Ment Dis 1987;
175:208-12.
80 Fleming JAE, Fleetham JA. A case report of obstructive
sleep apnea in a patient with bipolar affective disorder.
Can 7 Psychiatry 1985;30:437-9.
81 Berretini WH. Paranoid psychosis and sleep apnea syndrome. Am Y Psychiatry 1980;137:493-4.
82 Millman RP, Fogel BS, McNamara ME, Carlisle CC.
Depression as a manifestation of obstructive sleep apnea:
reversal with nasal continuous positive airway pressure.
Y Clin Psychiatry 1989;50:348-5 1.
83 Berry DTR, Phillips BA, Cook YR, Schmitt FA, Gilmore
RL, Patel R, et al. Sleep-disordered breathing in healthy
aged persons: possible daytime sequelae. J Geront 1987;
42:620-6.
84 Knight H, Millman RP, Gur RC, Saykin AJ, Doherty JU,
Pack Al. Clinical significance of sleep apnea in the elderly.
Am Rev Respir Dis 1987;136:845-50.
85 Dickel MJ, Mosko SS. Morbidity cut-offs for sleep apnea
and periodic leg movements in predicting subjective complaints in seniors. Sleep 1990;13:155-66.
86 Bliwise DL. Sleep in normal aging and dementia. Sleep
1993;16:40-81.
87 Bliwise DL, Yesavage JA, Tinklenberg JR, Dement WC.
Sleep apnea in Alzheimer's disease. NeurobiolAging 1989;
10:343-6.
88 Erkinjuntti T, Partinen M, Sulkava R. Telakivi T, Salmi
T, Tilvis R. Sleep apnea in multiinfarct dementia and
Alzheimer's disease. Sleep 1987;10:419-25.
89 Santamaria JD, Prior JC, Fleetham JA. Reversible reproductive dysfunction in men and obstructive sleep
apnoea. Clin Endocnnol 1988;28:461-70.
90 Grunstein RR, Handelsman DJ. Lawrence SJ, Blackwell
C, Caterson ID, Sullivan CE. Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive
airways pressure therapy. J Clin Endocrinol Metab 1989;
68:352-8.
91 Goldman JM, Ireland RM, Berthon-Jones M, Grunstein
RR, Sullivan CE, Biggs JC. Erythropoietin concentrations
in obstructive sleep apnoea. Thorax 1991;46:25-7.
92 McKeon JL, Saunders NA, Murree-Allen K, Olson LG,
Gyulay S, Dickeson J, et al. Urinary uric acid:creatinine
ratio, serum erythropoietin, and blood 2,3-diphosphoglycerate in patients with obstructive sleep apnea. Am
Rev Respir Dis 1990;142:8-13.
93 Krieger J, Sforza E, Delanoe C, Petiau C. Decrease in
Downloaded from http://thorax.bmj.com/ on May 2, 2017 - Published by group.bmj.com
Ferguson, Fleetham
1004
94
95
96
97
98
99
100
haemotocrit with continuous positive airway pressure
treatment in obstructive sleep apnoea patients. Eur Respir
1992;5:228-33.
Ichioka M, Hirata Y, Inase N, Tojo N, Yoshizawa M,
Chida M, et al. Changes of circulating atrial natriuretic
peptide and antidiuretic hormone in obstructive sleep
apnea syndrome. Respiration 1992;59:164-8.
Krieger J, Laks L, Wilcox I, Grunstein RR, Costas LJV,
McDougall JG, et al. Atrial natriuretic peptide release
during sleep in patients with obstructive sleep apnoea
before and during treatment with nasal continuous positive airway pressure. Clin Sci 1989;77:407-11.
Lin CC, Tsan KW, Lin CY. Plasma levels of atrial natriuretic factor in moderate to severe obstructive sleep apnea
syndrome. Sleep 1993;16:37-9.
Krieger J, Follenius M, Sforza E, Brandenberger G, Peter
JD. Effects of treatment with nasal continuous positive
airway pressure on atrial natriuretic peptide and arginine
vasopressin release during sleep in patients with obstructive sleep apnoea. Clin Sci 1991;80:443-9.
Warley ARH, Stradling JR. Abnormal diurnal variation in
salt and water excretion in patients with obstructive sleep
apnoea. Clin Sci 1988;74:183-5.
Rodenstein DO, D'OdemontJP, Pieters T, Aubert-Tulkens
G. Diurnal and nocturnal diuresis and natriuresis in
obstructive sleep apnea. Am Rev Respir Dis 1992;145:
1367-71.
Chaudhary BA, Sklar AH, Chaudhary TK, Kolbeck RC,
Speir WA Jr. Sleep apnea, proteinuria, and nephrotic
syndome. Sleep 1988;11:69-74.
101 Sklar AH, Chaudhary BA, Harp R. Nocturnal urinary
protein excretion rates in patients with sleep apnea. Nephron 1989;51:35-8.
102 Partinen M, Jamieson A, Guilleminault CG. Long-term
outcome for obstructive sleep apnea syndrome patients
- mortality. Chest 1988;94:1200-4.
103 He J, Kryger MH, Zorick FJ, Conway W, Roth T. Mortality
and apnea index in obstructive sleep apnea - experience
in 385 male patients. Chest 1988;94:9-14.
104 Partinen M, Guilleminault C. Daytime sleepiness and
vascular morbidity at seven-year follow-up in obstructive
sleep apnea patients. Chest 1990;97:27-32.
105 Keenan SP, Burt H, Ryan CF, Fleetham JA. Long-term
survival of patients with obstructive sleep apnea treated
by uvulopalatopharyngoplasty or nasal CPAP. Chest 1994;
105:155-9.
106 Ancoli-Israel S, Klauber MR, Kripke DF, Parker L,
Cobarrubias M. Sleep apnea in female patients in a
nursing home: increase risk of mortality. Chest 1989;96:
1054-8.
107 Bliwise D, Bliwise N, Partinen M, Pursley A, Dement W.
Sleep apnea and mortality in an aged cohort. Am Public
Health 1988;78:544-7.
108 Shepard JW. Hemodynamics in obstructive sleep apnea.
In: Fletcher E, ed. Abnormalities of respiration during sleep.
Orlando, Florida: Grune and Stratton, 1986:46.
Downloaded from http://thorax.bmj.com/ on May 2, 2017 - Published by group.bmj.com
Sleep-related breathing disorders. 4.
Consequences of sleep disordered breathing.
K A Ferguson and J A Fleetham
Thorax 1995 50: 998-1004
doi: 10.1136/thx.50.9.998
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