(Stroke. 1996;27:401-407.)
© 1996 American Heart Association, Inc.
Articles |
Investigating the Relationship Between Stroke and Obstructive Sleep Apnea
From the Department of Neurology, Sleep Disorders Center (M.E.D., T.Y., Z.-Y.R.); the Department of Internal Medicine, Division of Cardiovascular Diseases (V.K.S.); and the Department of Preventive Medicine (M.B.Z.), University of Iowa College of Medicine, Iowa City.
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Abstract |
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Background and Purpose We aimed to prospectively determine whether the incidence of obstructive sleep apnea in patients with recent stroke was significantly different from that of a sex- and age-matched control group with no major medical problems.
Methods We prospectively performed overnight polysomnography in 24 patients with a recent stroke (13 men and 11 women; mean age [±SD], 64.6±10.4 years) and 27 subjects without stroke (13 men and 14 women; mean age, 61.6±8.8 years). Patients with either ischemic or hemorrhagic stroke were entered into this study. Polysomnographic evaluations were performed within approximately 2 to 5 weeks after each patient's stroke.
Results Obstructive sleep apnea was found in 10 of 13 men with stroke (77%) and in only 3 of 13 male subjects without stroke (23%) (P=.0169). Seven of 11 women with stroke (64%) had obstructive sleep apnea, while only 2 of 14 female subjects without stroke (14%) had obstructive sleep apnea (P=.0168). For men with stroke, the mean apnea/hypopnea index (±SE) was 21.5±4.2 events per hour, while for male subjects without stroke it was 4.8±1.8 events per hour (P=.0014). For women with stroke the mean apnea/hypopnea index was 31.6±8.8 events per hour, while for female subjects without stroke it was 2.9±1.6 events per hour (P=.0024). The 4-year mortality for patients with stroke was 20.8%. All patients with stroke who died had obstructive sleep apnea.
Conclusions Patients with stroke have an increased incidence of obstructive sleep apnea compared with normal sex- and age-matched control subjects. Hypoxia and hemodynamic responses to obstructive sleep apnea may have predisposed these patients to stroke.
Key Words: polysomnography • risk factors • sleep apnea syndromes
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Introduction |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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Among known risk factors for stroke are age, sex, hypertension, diabetes mellitus, smoking, and a history of cardiovascular disease.1 Obstructive sleep apnea, however, is not widely considered as a risk factor for stroke. A common associated finding of obstructive sleep apnea is snoring.2 3 Palomake et al4 studied 167 men with stroke and found that 35.5% experienced their strokes during sleep. Using stepwise multiple logistic regression analysis, they showed that among possible risk factors for stroke (snoring, age, body mass index, smoking, alcohol consumption, and diabetes mellitus), only snoring was significantly related to stroke in sleep.
Palomake5 subsequently reported that the odds ratio of snoring as a risk factor for stroke was strongly increased if snoring was accompanied by excessive daytime sleepiness and obesity. These findings suggest that obstructive sleep apnea syndrome is a risk factor for stroke. No definitive diagnosis of obstructive sleep apnea was made in this patient population, however.
Complete overnight polysomnographic monitoring is the usual method used to confirm the presence and severity of obstructive sleep apnea, but to date few studies using polysomnography have addressed the relationship between obstructive sleep apnea and stroke.6 7 8 9 Using standard polysomnography, we studied male and female patients with stroke for the presence of obstructive sleep apnea and compared them with normal sex- and age-matched control subjects.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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Prospectively, information concerning known risk factors for both stroke (hypertension, cardiac disease, diabetes mellitus, and smoking)1 and obstructive sleep apnea (hypertension,10 11 cardiac disease,12 obesity,13 14 snoring,2 and excessive daytime sleepiness15 ) was collected from 24 inpatients with stroke and 27 subjects without stroke (Table 1
). All subjects
underwent complete overnight polysomnographic studies (Tables 2
and 3). These studies were approved by our
institutional committee on human experimentation, and written consent
was obtained.
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Patients were recruited from persons hospitalized in our Acute Stroke
Care and Monitoring Unit at the University of Iowa Hospitals and
Clinics. Individuals were admitted with acute stroke or for care of
stroke-related problems. Patients were diagnosed with stroke on the
basis of a full clinical assessment with detailed neurological
examinations and imaging studies of the brain with the use of CT and/or
MRI (Tables 4 and 5). Subjects without
stroke were recruited primarily from the local population. These
individuals responded to fliers placed in the Iowa City Senior Citizens
Center and throughout the University of Iowa Hospitals and Clinics.
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One investigator (M.E.D.) was responsible for entering all subjects into this study. Over a 94-day period, 43 consecutive inpatients with stroke-related admissions were considered for polysomnographic evaluation. The patients were evaluated on a first admitted, first studied basis. Because of the capacities of the sleep laboratory, only 1 to 3 study subjects (stroke and nonstroke) could be evaluated per week. Thirteen potential study patients were discharged before they could be entered into the study. Another patient experienced complete resolution of neurological symptoms before the study, 3 were considered by staff physicians to be too ill for evaluation, and 2 refused polysomnography. Twenty-two patients had first strokes and 2 had histories of one prior stroke. Polysomnograms were performed on average 15.7 days after stroke.
A standard polygraph (model 1A97, Nicolet Instrument Corp) was used to record the electroencephalogram, electro-oculogram, electromyogram of chin and bilateral tibialis anterior, electrocardiogram, airflow, and chest wall movement. Audio-video information was captured with the use of a black-and-white camera. The studies were performed and scored in a sleep center accredited by the American Sleep Disorders Association by technicians and physicians board certified in Sleep Disorders Medicine, using the criteria of Rechtschaffen and Kales.16
Respiratory events were classified as apneas and hypopneas.6 Apneas are defined as events during which airflow is absent, and hypopneas are events during which airflow is reduced by greater than 50% in association with oxygen desaturation values. Apneas and hypopneas are further classified as obstructive, central, or mixed. Obstructive apneas are events during which respiratory effort continues, whereas during central apneas respiratory effort is absent. A mixed apnea is defined as an event with an initial central component followed by an obstructive component.
To be considered significant, abnormal respiratory events had to persist for a minimum of 10 seconds and/or occur in association with an arousal and/or a decrease in oxygen saturation of 3% or more. Any individual with an apnea/hypopnea index (the average number of obstructive events occurring per hour of sleep) greater than or equal to 10 events per hour and/or any number of obstructive events associated with an oxygen saturation low value of less than or equal to 86% was given the diagnosis of obstructive sleep apnea.6 17 18 19 20
Fisher's exact test was used to examine the association between
stroke
and the presence of obstructive sleep apnea, hypertension, cardiac
disease, diabetes mellitus, and a history of smoking, snoring, daytime
sleepiness, and death. The Wilcoxon rank sum test was used to
compare the apnea/hypopnea indices between stroke and nonstroke
subjects. A two-way ANOVA, with stroke and sex as the factors in
the analysis, was used to compare lowest oxygen saturation
values between stroke and nonstroke subjects. A three-way ANOVA,
with stroke, apnea, and sex as the factors in the analysis, was
used to compare body mass indices and oxygen saturation levels during
wakefulness. The 
2 goodness of fit test was used
to assess the significance of stroke occurring during sleep versus
during the waking hours.
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Results |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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No stroke or control subjects demonstrated central sleep apnea as their primary sleep pathology. Obstructive sleep apnea was found in 10 of 13 men with stroke (77%) and in only 3 of 13 male control subjects (23%) (P=.0169). Seven of 11 women with stroke (64%) had obstructive sleep apnea, while only 2 of 14 female control subjects (14%) had obstructive sleep apnea (P=.0168) (Table 1
and Fig 1).
For men with
stroke the mean apnea/hypopnea index was 21.5±4.2 events per hour,
while for male control subjects it was 4.8±1.8 events per hour
(P=.0014) (Table 2). For women with stroke the
mean
apnea/hypopnea index was 31.6±8.8 events per hour, while for female
control subjects it was 2.9±1.6 events per hour
(P=.0024)
(Table 3). For men with stroke the median apnea/hypopnea index
was 16.8
events (range, 0.8 to 47.0 events per hour), while for male control
subjects it was 1.4 (range, 0 to 21.0 events per hour). For women with
stroke the median apnea/hypopnea index was 38.4 (range, 0 to 78.9
events per hour), while for female control subjects it was 0 (range, 0
to 16 events per hour) (Fig 2).
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Overall the mean lowest recorded values for oxygen saturation during sleep (±SE) were significantly lower in the patients (85.0±1.5%) than in subjects without a history of stroke (90.6±0.6%) (P=.0006). There was no significant difference in the values for oxygen saturation during wakefulness between patients and control subjects (respective means, 94.6±0.4% and 95.5±0.4%; P=.1) or between apneics and nonapneics (patients and control subjects) in general (respective means, 94.9±0.4% and 95.2±0.4%; P=.6).
Nine of 13 men with stroke (69%) had histories of hypertension
compared with 1 of 13 (8%) male control subjects (P=.0036).
Nine of 11 women with stroke (82%) had histories of hypertension
compared with 2 of 14 (14%) of the female control subjects
(P=.0012) (Table 1).
A history of cardiac disease (myocardial infarction, arrhythmias, conduction defects, and congestive heart failure) was present in 4 of 13 (31%) of the men with stroke and in none of the nonstroke men (P=.0957). A history of cardiac disease was present in 6 of 11 (55%) of the women with stroke and in 2 of 14 (14%) of the nonstroke women (P=.0810).
No history of hypertension or cardiac disease was reported for 5 of our stroke patients and 24 of our nonstroke subjects. Four of 5 nonhypertensive/non-cardiac disease stroke patients (80%) had obstructive sleep apnea, while only 4 of these nonhypertensive/non-cardiac disease nonstroke individuals (17%) suffered from obstructive sleep apnea (P=.0128). The mean apnea/hypopnea index in the group of nonhypertensive/non-cardiac disease stroke patients was 35.6±10.2, while the mean apnea/hypopnea index in the nonhypertensive/non-cardiac disease nonstroke group was significantly lower at 3.6±1.2 (P=.0100). In addition, there was no significant difference in the mean body mass index of the nonhypertensive/non-cardiac disease subgroup of stroke patients (24.9±1.2) and the nonhypertensive/non-cardiac disease subgroup of nonstroke subjects (25.1±0.6) (P=.9).
Only 1 woman control subject had diabetes mellitus, while 7 stroke patients (2 men and 5 women) had diabetes. Significantly more men with stroke (12 of 13) reported a history of smoking compared with the male nonstroke population (2 of 13) (P=.0002), while no significant difference was reported between women with stroke (3 of 11) and nonstroke women (1 of 14) (P=.2878).
The mean body mass index in women with stroke (with or without obstructive sleep apnea) was significantly higher than that of nonstroke women without apnea. There was no significant difference in the mean body mass index between men with stroke and nonstroke men.
Fourteen of the stroke patients and 3 of the control subjects were unable to comment on their snoring histories since they did not know if they snored (they often lived alone) or were occasionally unable to respond because of the severity of their stroke and because no family members or friends were available who could answer the question knowingly. Of the remaining 10 stroke patients, all reported a history of snoring. Interestingly, of the 17 stroke patients with unequivocal polysomnographic evidence of obstructive sleep apnea, no significant snoring was evident in 7 when an overhead room microphone was used.
Similar problems were experienced with obtaining histories of daytime
sleepiness. In regard to sleepiness before stroke, no accurate report
could be obtained from 6 patients, 10 denied prestroke sleepiness, and
8 complained of prestroke sleepiness (6 mild and 2 severe). In the
control population, prepolysomnography questionnaires revealed no
sleepiness in 19 individuals, while 8 reported sleepiness (6 mild and 2
moderate) (Table 1). It is of interest that in poststroke,
prepolysomnographic questionnaires, 15 patients (68%) in the stroke
population complained of sleepiness (6 mild, 6 moderate, and 3 severe),
while 7 denied prestudy sleepiness and 2 were aphasic and unresponsive;
as a result, no such assessment was possible. These findings in all
probability were associated with the multiple medical concomitants of
recent stroke.
Although 1 patient was receiving a combination of propoxyphene napsylate and aspirin as needed, in general both populations were receiving a wide variety of medications not generally recognized to cause obstructive sleep apnea. All patients were taking medications, including antihypertensives, anticoagulants, antiplatelet aggregating agents, diuretics, and hypoglycemic drugs. Two patients took antihistamines on an as-needed basis, while 1 received haloperidol for poststroke hemiballismus. Of the 26 control subjects, only 6 men and 6 women were not receiving medications, many were taking over-the-counter medications (aspirin, nonsteroidal anti-inflammatories, and "allergy" medications), 3 were taking antidepressants, 2 were taking sodium warfarin, 2 received a combination of digoxin and furosemide, and 1 was receiving thyroid replacement.
Of the 24 patients with stroke, 13 suffered their strokes during sleep.
One of 4 of the hemorrhagic and 12 of 20 of the ischemic
strokes occurred during sleep (Tables 4 and 5).
Hemorrhagic events were
localized to the basal ganglia, cerebellum, and thalamus, while
ischemic events were documented throughout the brain and in the
brain stem. Only 1 of the 2 patients who suffered brain stem strokes
had obstructive sleep apnea.
We were able to perform repeat polysomnograms 3 to 5 months later on 4 stroke patients with nocturnal obstructive respiratory events. Only 1 of these patients received interim continuous positive airway pressure therapy. All of these patients demonstrated obstructive sleep apnea on reevaluation.
Over a 4-year period, reassessments were made on all stroke patients
and on all but 3 control subjects (individuals had moved with no
forwarding addresses or telephone numbers). Only stroke patients with
obstructive sleep apnea (n=5; 3 men, 2 women) and 1 male control
subject died (Table 1). The mean apnea/hypopnea index
(±SE) of the
stroke patients who died was 41.3±12.7 events per hour, while in
stroke patients who did not die the mean apnea/hypopnea index was
22.1±4.5 events per hour (P=.1263). One patient died of
congestive heart failure; 1 of a perforated colon, sepsis, and
myocardial infarction; 2 of pneumonia (1 as a result of aspiration);
and 1 of urosepsis. Of these 5 patients, only the patient with
urosepsis used continuous positive airway pressure therapy. The control
subject was a man without significant obstructive sleep apnea, who died
of prostatic carcinoma.
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Discussion |
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TopAbstractIntroductionSubjects and Methods Results Discussion References |
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Obstructive sleep apnea has been associated with hypertension and cardiovascular disease. To date, few studies that used polysomnography have suggested any relationship between obstructive sleep apnea and stroke.
Our interest in the association between obstructive sleep apnea and stroke was stimulated by a 34-year-old morbidly obese man, with severe obstructive sleep apnea, who awoke from sleep with stroke.21 The likeliest time for the occurrence of ischemic stroke is during sleep and in the first hour after awakening.22 Assuming that stroke has an equal probability of occurring at any time during a 24-hour period, 33% of all strokes would be expected to occur during the approximate 8-hour period of sleep. Our data indicate that a higher percentage of patients experienced stroke in sleep (54%, 13 of 24 subjects) than expected (P=.0304). Of the 5 patients with obstructive sleep apnea who died, 4 suffered their original stroke during sleep.
We have previously shown that obstructive respiratory events can elicit excessive sympathetic and parasympathetic activation, with consequent surges in blood pressure (up to 220/130 mm Hg) and bradyarrhythmias (including complete heart block and sinus pause).23 24 25 26 27 Hypoxia and hypoperfusion may predispose patients with obstructive sleep apnea to stroke, especially during sleep.
The temporal association between acute supratentorial central nervous system injury and a variety of respiratory abnormalities has led to the assumption that stroke may cause obstructive sleep apnea.9 The literature does not support this. Plum and Posner28 described stuporous and comatose patients with central transtentorial and rarely uncal herniation who demonstrate changes in their respiratory patterns (from eupneic to Cheyne-Stokes to hyperventilation and ataxic breathing) as injury progresses in a rostral-caudal manner from the diencephalon to the upper medulla.
Brain stem stroke and other disorders causing injury to the medullary respiratory centers have been reported to produce primarily central sleep apnea.29 30 These central apneas often appear as "Ondine's curse," in which no spontaneous respirations during sleep may occur and continuous ventilatory support while asleep may be required.29 This type of apnea occurs without a Cheyne-Stokes respiratory pattern.30
Cheyne-Stokes respiration implies bilateral neurological dysfunction deep in the cerebrum, in the diencephalon, and rarely as low as the upper pons.28 Studies concerning Cheyne-Stokes pattern respiration and stroke often do not distinguish between waking and sleeping states. Hudgel et al31 screened patients with unilateral cerebral strokes for Cheyne-Stokes-like respiratory patterns. When their patients were studied polysomnographically, they did not show any more respiratory periodicity than healthy elderly control subjects, who were not similarly screened. However, they had wider oscillations in tidal volume. Hudgel et al speculated that the widely oscillating respiratory patterns and obstructive apneas may have been present before the stroke and by inducing oscillations in cerebral vascular and tissue pressures, hypoxemia and reduced cerebral blood flow may have caused stroke.
The primary breathing abnormalities observed in the present study were obstructive events, with no subjects manifesting significant central sleep apnea or Cheyne-Stokes respiration while awake or asleep. Even after continuous positive airway pressure therapy was initiated, none of our patients had evidence of any underlying central apneas or obvious Cheyne-Stokes respiratory patterns. In addition, obstructive sleep apnea does not appear to be a transient accompaniment of stroke, since our patients demonstrated persistence of sleep-related obstructive respiratory events when repeated polysomnographic studies were performed within a 3- to 5-month period.
Obstructive sleep apnea has been associated with chronic hypertension and heart disease. Tilkian et al32 hypothesized that repetitive hypertensive events associated with nocturnal apneas might lead to sustained hemodynamic abnormalities. Although many of our patients had hypertension and/or cardiac disease, when we selected out these factors obstructive sleep apnea appeared to still have a relatively high prevalence in the stroke population. Additionally, in these selected subgroups even the mean body mass indices did not differ significantly from those of the nonstroke patients.
Although a history of snoring has been associated with hypertension, cardiovascular disease, and stroke, snoring is very difficult to quantify. A large number of our patients were unsure or unable to comment on their snoring history. In this population an important element of the obstructive sleep apnea syndrome is therefore absent. Even in the controlled laboratory setting, patients with unequivocal polysomnographically documented obstructive respiratory events may not demonstrate significant snoring.
This study indicates that patients with stroke have a high incidence of significant obstructive sleep apnea compared with normal sex- and age-matched control subjects. Since both obstructive sleep apnea and stroke are frequently seen in patients with hypertension and heart disease, we cannot state that the association is not an artifact of other concomitant medical problems or unequivocally state that obstructive sleep apnea is not the result of stroke. However, since greater than 50% of the patients in this study suffered their strokes during sleep and our data contradict the assumption that patients with stroke have an increased frequency of Cheyne-Stokes breathing, we speculate that the hypoxemia and autonomic responses associated with obstructive sleep apnea may produce acute and chronic changes that predispose patients not only to hypertension and cardiovascular disease but also to stroke.
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Acknowledgments |
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This study was supported by Biomedical Research Support grant RR 05372 from the Biomedical Research Support Branch, Division of Research Facilities and Resources, National Institutes of Health. Dr Somers was supported by grant HL-14388 from the National Heart, Lung, and Blood Institute and by the Council for Tobacco Research. We would like to acknowledge the assistance of Drs Deborah C. Lin-Dyken, Harold P. Adams, Jr, and Patricia H. Davis in the preparation of this manuscript.
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Footnotes |
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Reprint requests to Dr Mark E. Dyken, Department of Neurology, Sleep Disorders Center, University of Iowa, Iowa City, IA 52242.
Review of this manuscript was directed by José Biller, MD. Because of the conflict of interest, the Editor-in-Chief had absolutely no involvement with reviews of this manuscript.
Received October 19, 1995; revision received December 1, 1995; accepted December 1, 1995.
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N. J. Buchner, B. M. Sanner, J. Borgel, and L. C. Rump Continuous Positive Airway Pressure Treatment of Mild to Moderate Obstructive Sleep Apnea Reduces Cardiovascular Risk Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1274 - 1280. [Abstract] [Full Text] [PDF]
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 A.-M. Park and Y. J. Suzuki Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice J Appl Physiol, May 1, 2007; 102(5): 1806 - 1814. [Abstract] [Full Text] [PDF]
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G. E. Foster, P. J. Hanly, M. Ostrowski, and M. J. Poulin Effects of Continuous Positive Airway Pressure on Cerebral Vascular Response to Hypoxia in Patients with Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., April 1, 2007; 175(7): 720 - 725. [Abstract] [Full Text] [PDF]
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P. Coruzzi, M. Gualerzi, E. Bernkopf, L. Brambilla, V. Brambilla, V. Broia, C. Lombardi, and G. Parati Autonomic Cardiac Modulation in Obstructive Sleep Apnea: Effect of an Oral Jaw-Positioning Appliance. Chest, November 1, 2006; 130(5): 1362 - 1368. [Abstract] [Full Text] [PDF]
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 R. Munoz, J. Duran-Cantolla, E. Martinez-Vila, J. Gallego, R. Rubio, F. Aizpuru, and G. De La Torre Severe Sleep Apnea and Risk of Ischemic Stroke in the Elderly Stroke, September 1, 2006; 37(9): 2317 - 2321. [Abstract] [Full Text] [PDF]
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J L Lattimore, I Wilcox, M Skilton, M Langenfeld, and D S Celermajer Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation Thorax, June 1, 2006; 61(6): 491 - 495. [Abstract] [Full Text] [PDF]
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 E. H. H. Chiu, C.-S. Liu, T.-Y. Tan, and K.-C. Chang Venturi mask adjuvant oxygen therapy in severe acute ischemic stroke. Arch Neurol, May 1, 2006; 63(5): 741 - 744. [Abstract] [Full Text] [PDF]
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C. L. Bassetti, M. Milanova, and M. Gugger Sleep-Disordered Breathing and Acute Ischemic Stroke: Diagnosis, Risk Factors, Treatment, Evolution, and Long-Term Clinical Outcome Stroke, April 1, 2006; 37(4): 967 - 972. [Abstract] [Full Text] [PDF]
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M. A. Martinez-Garcia, R. Galiano-Blancart, J.-J. Soler-Cataluna, L. Cabero-Salt, and P. Roman-Sanchez Improvement in nocturnal disordered breathing after first-ever ischemic stroke: role of Dysphagia. Chest, February 1, 2006; 129(2): 238 - 245. [Abstract] [Full Text] [PDF]
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M. Arzt, T. Young, L. Finn, J. B. Skatrud, and T. D. Bradley Association of Sleep-disordered Breathing and the Occurrence of Stroke Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1447 - 1451. [Abstract] [Full Text] [PDF]
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C. Selic, M. M. Siccoli, D. M. Hermann, and C. L. Bassetti Blood Pressure Evolution After Acute Ischemic Stroke in Patients With and Without Sleep Apnea Stroke, December 1, 2005; 36(12): 2614 - 2618. [Abstract] [Full Text] [PDF]
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 H. K. Yaggi, J. Concato, W. N. Kernan, J. H. Lichtman, L. M. Brass, and V. Mohsenin Obstructive Sleep Apnea as a Risk Factor for Stroke and Death. N. Engl. J. Med., November 10, 2005; 353(19): 2034 - 2041. [Abstract] [Full Text] [PDF]
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M. A. Martinez-Garcia, R. Galiano-Blancart, P. Roman-Sanchez, J.-J. Soler-Cataluna, L. Cabero-Salt, and E. Salcedo-Maiques Continuous Positive Airway Pressure Treatment in Sleep Apnea Prevents New Vascular Events After Ischemic Stroke Chest, October 1, 2005; 128(4): 2123 - 2129. [Abstract] [Full Text] [PDF]
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M. Yamauchi, H. Nakano, J. Maekawa, Y. Okamoto, Y. Ohnishi, T. Suzuki, and H. Kimura Oxidative Stress in Obstructive Sleep Apnea Chest, May 1, 2005; 127(5): 1674 - 1679. [Abstract] [Full Text] [PDF]
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 M. Dunleavy, M. Dooley, D. Cox, and A. Bradford Chronic intermittent asphyxia increases platelet reactivity in rats Exp Physiol, May 1, 2005; 90(3): 411 - 416. [Abstract] [Full Text] [PDF]
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R. W. Peters Obstructive Sleep Apnea and Cardiovascular Disease Chest, January 1, 2005; 127(1): 1 - 3. [Full Text] [PDF]
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 O. Parra, A. Arboix, J.M. Montserrat, L. Quinto, S. Bechich, and L. Garcia-Eroles Sleep-related breathing disorders: impact on mortality of cerebrovascular disease Eur. Respir. J., August 1, 2004; 24(2): 267 - 272. [Abstract] [Full Text] [PDF]
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 J. M. Parish and V. K. Somers Obstructive Sleep Apnea and Cardiovascular Disease Mayo Clin. Proc., August 1, 2004; 79(8): 1036 - 1046. [Abstract] [PDF]
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T. A. Bowdle Nocturnal Arterial Oxygen Desaturation and Episodic Airway Obstruction After Ambulatory Surgery Anesth. Analg., July 1, 2004; 99(1): 70 - 76. [Abstract] [Full Text] [PDF]
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G J Gibson Sleep disordered breathing and the outcome of stroke Thorax, May 1, 2004; 59(5): 361 - 363. [Full Text] [PDF]
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D Schlosshan and M W Elliott Sleep * 3: Clinical presentation and diagnosis of the obstructive sleep apnoea hypopnoea syndrome Thorax, April 1, 2004; 59(4): 347 - 352. [Abstract] [Full Text] [PDF]
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T. Altay, E. R. Gonzales, T. S. Park, and J. M. Gidday Cerebrovascular inflammation after brief episodic hypoxia: modulation by neuronal and endothelial nitric oxide synthase J Appl Physiol, March 1, 2004; 96(3): 1223 - 1230. [Abstract] [Full Text] [PDF]
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M. E. Dyken, T. Yamada, C. L. Glenn, and H. A. Berger Obstructive sleep apnea associated with cerebral hypoxemia and death Neurology, February 10, 2004; 62(3): 491 - 493. [Abstract] [Full Text] [PDF]
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N. McArdle, R. L. Riha, M. Vennelle, E. L. Coleman, M. S. Dennis, C. P. Warlow, and N. J. Douglas Sleep-Disordered Breathing as a Risk Factor for Cerebrovascular Disease: A Case-Control Study in Patients With Transient Ischemic Attacks Stroke, December 1, 2003; 34(12): 2916 - 2921. [Abstract] [Full Text] [PDF]
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 A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo Jr, D. W. Jones, B. J. Materson, S. Oparil, J. T. Wright Jr, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension, December 1, 2003; 42(6): 1206 - 1252. [Abstract] [Full Text] [PDF]
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R. von Kanel and J. E. Dimsdale Hemostatic Alterations in Patients With Obstructive Sleep Apnea and the Implications for Cardiovascular Disease Chest, November 1, 2003; 124(5): 1956 - 1967. [Abstract] [Full Text] [PDF]
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 P O Lundmark, G E Trope, and J G Flanagan The effect of simulated obstructive apnoea on intraocular pressure and pulsatile ocular blood flow in healthy young adults Br J Ophthalmol, November 1, 2003; 87(11): 1363 - 1369. [Abstract] [Full Text] [PDF]
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 A. S. M. Shamsuzzaman, B. J. Gersh, and V. K. Somers Obstructive Sleep Apnea: Implications for Cardiac and Vascular Disease JAMA, October 8, 2003; 290(14): 1906 - 1914. [Abstract] [Full Text] [PDF]
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A. I. Pack Should a Pharmaceutical Be Approved for the Broad Indication of Excessive Sleepiness? Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 109 - 111. [Full Text] [PDF]
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 J. Harbison, G.A. Ford, O.F.W. James, and G.J. Gibson Sleep-disordered breathing following acute stroke QJM, November 1, 2002; 95(11): 741 - 747. [Abstract] [Full Text] [PDF]
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D. S.C. Hui, D. K.L. Choy, L. K.S. Wong, F. W.S. Ko, T. S.T. Li, J. Woo, and R. Kay Prevalence of Sleep-Disordered Breathing and Continuous Positive Airway Pressure Compliance* : Results in Chinese Patients With First-Ever Ischemic Stroke Chest, September 1, 2002; 122(3): 852 - 860. [Abstract] [Full Text] [PDF]
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P.M. Turkington, J. Bamford, P. Wanklyn, and M.W. Elliott Prevalence and Predictors of Upper Airway Obstruction in the First 24 Hours After Acute Stroke Stroke, August 1, 2002; 33(8): 2037 - 2042. [Abstract] [Full Text] [PDF]
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 S. Boyer and V. Kapur Obstructive Sleep Apnea: Its Relevance in the Care of Diabetic Patients Clin. Diabetes, July 1, 2002; 20(3): 126 - 132. [Abstract] [Full Text] [PDF]
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L. DYUGOVSKAYA, P. LAVIE, and L. LAVIE Increased Adhesion Molecules Expression and Production of Reactive Oxygen Species in Leukocytes of Sleep Apnea Patients Am. J. Respir. Crit. Care Med., April 1, 2002; 165(7): 934 - 939. [Abstract] [Full Text] [PDF]
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A. Iranzo, J. Santamaria, J. Berenguer, M. Sanchez, and A. Chamorro Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction Neurology, March 26, 2002; 58(6): 911 - 916. [Abstract] [Full Text] [PDF]
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R. S. T. LEUNG and T. DOUGLAS BRADLEY Sleep Apnea and Cardiovascular Disease Am. J. Respir. Crit. Care Med., December 15, 2001; 164(12): 2147 - 2165. [Full Text] [PDF]
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R. B. FOGEL, A. MALHOTRA, G. PILLAR, J. K. EDWARDS, J. BEAUREGARD, S. A. SHEA, and D. P. WHITE Genioglossal Activation in Patients with Obstructive Sleep Apnea versus Control Subjects . Mechanisms of Muscle Control Am. J. Respir. Crit. Care Med., December 1, 2001; 164(11): 2025 - 2030. [Abstract] [Full Text] [PDF]
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T. MOOE, K. A. FRANKLIN, K. HOLMSTROM, T. RABBEN, and U. WIKLUND Sleep-disordered Breathing and Coronary Artery Disease . Long-term Prognosis Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1910 - 1913. [Abstract] [Full Text] [PDF]
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O. Parra Sleep-disordered breathing and stroke: is there a rationale for treatment? Eur. Respir. J., October 1, 2001; 18(4): 619 - 622. [Full Text] [PDF]
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T.E. Wessendorf, Y-;M. Wang, A.F. Thilmann, U. Sorgenfrei, N. Konietzko, and H. Teschler Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke Eur. Respir. J., October 1, 2001; 18(4): 623 - 629. [Abstract] [Full Text] [PDF]
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U. C. GUIDRY, L. A. MENDES, J. C. EVANS, D. LEVY, G. T. O'CONNOR, M. G. LARSON, D. J. GOTTLIEB, and E. J. BENJAMIN Echocardiographic Features of the Right Heart in Sleep-Disordered Breathing . The Framingham Heart Study Am. J. Respir. Crit. Care Med., September 15, 2001; 164(6): 933 - 938. [Abstract] [Full Text] [PDF]
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V. Mohsenin and A. Culebras Sleep-Related Breathing Disorders and Risk of Stroke Editorial Comment : Balancing Sleep and Breathing Stroke, June 1, 2001; 32(6): 1271 - 1278. [Abstract] [Full Text] [PDF]
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 R. B. Fogel, A. Malhotra, G. Pillar, S. D. Pittman, A. Dunaif, and D. P. White Increased Prevalence of Obstructive Sleep Apnea Syndrome in Obese Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1175 - 1180. [Abstract] [Full Text]
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A. S. M. Shamsuzzaman and V. K. Somers Fibrinogen, Stroke, and Obstructive Sleep Apnea . An Evolving Paradigm of Cardiovascular Risk Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2018 - 2020. [Full Text]
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T. E. WESSENDORF, A. F. THILMANN, Y.-M. WANG, A. SCHREIBER, N. KONIETZKO, and H. TESCHLER Fibrinogen Levels and Obstructive Sleep Apnea in Ischemic Stroke Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2039 - 2042. [Abstract] [Full Text]
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M. Kato, P. Roberts-Thomson, B. G. Phillips, W. G. Haynes, M. Winnicki, V. Accurso, and V. K. Somers Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea Circulation, November 21, 2000; 102(21): 2607 - 2610. [Abstract] [Full Text] [PDF]
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J.A. Harbison and G.J. Gibson Snoring, sleep apnoea and stroke: chicken or scrambled egg? QJM, October 1, 2000; 93(10): 647 - 654. [Full Text] [PDF]
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 A. H. FRIEDLANDER, L. A. WALKER, I. K. FRIEDLANDER, and A. L. FELSENFELD DIAGNOSING AND COMANAGING PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME J Am Dent Assoc, August 1, 2000; 131(8): 1178 - 1184. [Abstract] [Full Text] [PDF]
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O. PARRA, A. ARBOIX, S. BECHICH, L. GARCÍA-EROLES, J. M. MONTSERRAT, J. A. LÓPEZ, E. BALLESTER, J. M. GUERRA, and J. J. SOPEÑA Time Course of Sleep-related Breathing Disorders in First-Ever Stroke or Transient Ischemic Attack Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 375 - 380. [Abstract] [Full Text]
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 C. Bassetti and M. Aldrich Night time versus daytime transient ischaemic attack and ischaemic stroke: a prospective study of 110 patients J. Neurol. Neurosurg. Psychiatry, October 1, 1999; 67(4): 463 - 467. [Abstract] [Full Text] [PDF]
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W. D. Leslie, S. Wali, M. Kryger, N. C. Netzer, and K. P. Strohl Blood Flow of the Middle Cerebral Artery With Sleep-Disordered Breathing: Correlation With Obstructive Hypopneas • Response Stroke, January 1, 1999; 30 (1): 188 - 190. [Full Text] [PDF]
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K. Narkiewicz, N. Montano, C. Cogliati, P. J. H. van de Borne, M. E. Dyken, and V. K. Somers Altered Cardiovascular Variability in Obstructive Sleep Apnea Circulation, September 15, 1998; 98(11): 1071 - 1077. [Abstract] [Full Text] [PDF]
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N. Netzer, P. Werner, I. Jochums, M. Lehmann, and K. P. Strohl Blood Flow of the Middle Cerebral Artery With Sleep-Disordered Breathing : Correlation With Obstructive Hypopneas Stroke, January 1, 1998; 29(1): 87 - 93. [Abstract] [Full Text] [PDF]
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C. Bassetti, M. S. Aldrich, and D. Quint Sleep-Disordered Breathing in Patients With Acute Supra- and Infratentorial Strokes : A Prospective Study of 39 Patients Stroke, September 1, 1997; 28(9): 1765 - 1772. [Abstract] [Full Text]
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 J. Wright, R. Johns, I. Watt, A. Melville, and T. Sheldon Health effects of obstructive sleep apnoea and the effectiveness of continuous positive airways pressure: a systematic review of the research evidence BMJ, March 22, 1997; 314(7084): 851 - 851. [Abstract] [Full Text]
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