|
|
||||||||
Guest Access | Sign In via User Name/Password |
|||||||||
* From the Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Correspondence to: David S.C. Hui, MBBS, FCCP, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong; e-mail: dschui{at}cuhk.edu.hk
| Abstract |
|---|
|
|
|---|
Design: A case-controlled study.
Setting: A university hospital.
Measurements and results: We recruited 23 women and 28 men, who were admitted to the hospital within 4 days of stroke onset, with a mean (± SD) age of 64.2 ± 13.0 years and a body mass index (BMI) of 24.3 ± 4.4 kg/m2 for this study. Twenty-seven patients (53%) and 9 patients (17.6%), respectively, reported a history of snoring and severe daytime sleepiness prior to experiencing a stroke, while the mean Epworth sleepiness scale score was 6.8 ± 3.6. Polysomnography revealed 34 patients (67%) with an apnea-hypopnea index (AHI) of
10 events per hour, 31 patients (61%) with an AHI of
15 events per hour, and 25 patients (49%) with an AHI of
20 events per hour. Significant obstructive SDB, defined as an AHI of
20/h, was more prevalent in ischemic stroke patients than in control subjects (49% vs 24%, respectively; p = 0.04) and was associated with a higher BMI (p = 0.046). Among the 34 patients with an AHI of
10/h, CPAP titration was tolerated by 16 patients, but only 4 patients who had typical sleep apnea features proceeded to home CPAP treatment with objective compliance over a period of 3 months of 2.5 ± 0.6 h per night. A subgroup of 20 patients not receiving CPAP showed partial spontaneous improvement of SDB at 1 month (baseline AHI, 32.3 ± 17.6 events per hour; AHI at 1 month, 23.0 ± 18.8 events per hour; p = 0.01) with a trend toward improvement for the obstructive but no significant change for the central events, whereas no improvement in AHI was noted for the four patients receiving CPAP.
Conclusion: There is a high prevalence of obstructive SDB in patients who have experienced acute ischemic stroke, which, in many cases, is different from classic obstructive sleep apnea syndrome, and this is reflected by the lack of significant sleepiness, poor CPAP acceptance, and partial spontaneous improvement at 1 month.
Key Words: continuous positive airway pressure compliance ischemic stroke sleep-disordered breathing
| Introduction |
|---|
|
|
|---|
In a retrospective study by He et al,4 patients with an apnea index (AI) of > 20 events per hour had a higher morbidity and mortality related to vascular events than those with an AI of < 20 events per hour. Cross-sectional associations from the baseline examination of the Sleep Heart Health Study cohort have shown modest-to-moderate effects of SDB on various manifestations of cardiovascular diseases, and, relatively, SDB was more strongly associated with reported stroke and heart failure than with coronary artery disease.5 There is evidence that habitual snoring is a possible independent risk factor for hypertension6 and stroke,7 8 9 while other studies have implicated the obstructive type of SDB as a risk factor for stroke,10 11 12 13 14 15 poor functional outcome,12 and poststroke mortality.8 12
Cerebrovascular disease has been a leading cause of morbidity and mortality in HK in recent years. Intracranial occlusive disease is the most commonly found vascular lesion among our acute stroke patients.16
There are currently no published data in HK concerning the relationship between SDB and stroke. Introduced by Sullivan et al17
2 decades ago, nasal continuous positive airway pressure (CPAP) has remained the "gold standard" treatment for patients with OSAS, with a high level of acceptance and compliance in our OSAS patients without stroke.18
Despite growing evidence of an unexpectedly high prevalence of SDB, which has been arbitrarily defined as an AHI of
20 events per hour, of 28 to 68% and 22 to 80%, respectively, in the acute and rehabilitation phases among stroke victims,10
11
12
13
14
15
none of these studies have addressed the more practical issue of CPAP acceptance and compliance among stroke victims who have confirmed SDB.
In this study, we aimed to assess the following: (1) the prevalence of SDB in the acute phase; (2) whether there was any spontaneous improvement of SDB at 1 month; (3) factors that might predict the occurrence of a significant level of SDB; and (4) the acceptance and compliance of nasal CPAP treatment among our patients with significant SDB following a first-ever ischemic stroke.
| Materials and Methods |
|---|
|
|
|---|
Stroke Assessment
Cerebral CT scanning was performed within the first 24 h of hospital admission to exclude hemorrhagic stroke. Cardiovascular risk factors were recorded, and these included a history of hypertension (defined as previously documented BP of >140/90 mm Hg on at least two occasions or a requirement of antihypertensive medication before the ischemic stroke), diabetes mellitus (defined as a fasting plasma glucose level of > 7 mmol/L or the taking of antidiabetic medication before the stroke), hypercholesterolemia (defined as a fasting blood low-density lipoprotein cholesterol level of > 3.4 mmol/L or the taking of lipid-lowering medication before the stroke), smoking (defined by the number of pack-years smoked), and alcohol consumption (defined by the number of drinks ingested per week). Relevant medical history such as that for congestive heart failure, ischemic heart disease, and atrial fibrillation was documented.
Patients were assessed within the first 2 days of hospitalization by one of the investigators. The site of ischemic stroke was determined clinically and from cerebral CT scans, and was classified according to the classification by Bamford et al.19
The severity of the neurologic deficits was assessed using the national Institutes of Health (NIH) stroke scale (scale, 0 to 42); in general, an NIH score of
2 implies at least moderate severity.20
Functional ability was measured with the Barthel index (BI) [scale, 0 to 20], a widely used multifaceted scale that measures mobility and the activities of daily living. A BI of < 17 implies at least a moderate degree of functional impairment.21
Inclusion criteria included age of 30 to 80 years and the onset of first-ever ischemic stroke within 2 weeks. Exclusion criteria included hemorrhagic stroke, subjects who were in a stupor or coma, and those subjects with a deteriorating clinical state or any serious coexisting disease that would be likely to affect survival during the study period (eg, malignancy and unstable angina).
Sleep Study Assessment
Following a baseline stroke assessment, the Sleep and Health Questionnaire (SHQ)22
and the Epworth sleepiness scale (ESS)23
were administered to evaluate OSAS symptoms and subjective sleepiness, respectively, in the past month prior to the onset of ischemic stroke.
The SHQ has been reported previously to be a valid means of characterizing symptom distribution in population surveys of OSAS.22 The questionnaire contains 16 questions grouped into five factors (ie, functional impact of sleepiness, self-reported breathing disturbances, roommate-observed breathing disturbances, driving impairment, and insomnia) and has been shown to be useful in predicting the occurrence of sleep apnea. The evaluation of responses to the questionnaire utilized either a 5-point frequency scale (never, rarely, sometimes, frequently, and almost always) or a 6-point Likert scale, which graded the severity of the symptoms. The responses were categorized as being mild, moderate, and severe for the purpose of data analysis.
The ESS is a questionnaire assessing the likelihood of falling asleep in eight different situations in recent times.23 When accurate assessment could not be performed on the patient due to aphasia or cognitive impairment, information was obtained from the spouse or close relatives.
Additional questions were included to document the use of alcohol and the subjects sleeping habits, including the subjects usual sleep schedule and, particularly, the sleep quality the night before beginning the sleep study.
All patients were studied with overnight polysomnography (Alice 4; Healthdyne; Atlanta, GA) to assess objectively the degree of SDB. Polysomnography was performed within 3 days of the initial hospital admission between 10 PM and 7 AM. Overnight polysomnography recorded EEG, electro-oculogram, submental electromyogram, bilateral anterior tibial electromyogram, ECG, chest and abdominal wall movement by inductance plethysmography and airflow by a nasal pressure transducer (PTAF 2; Pro-Tech; Woodinville, WA), which was backed up by oronasal airflow measured with a thermistor and finger pulse oximetry, as in our previous study.18
Sleep stages were scored according to the standard criteria of Rechtshaffen and Kales.24
Apnea was defined as the cessation of airflow for > 10 s, and hypopnea was defined as a reduction of airflow of
50% for 10 s plus an oxygen desaturation of > 3% or an arousal. Predominantly obstructive SDB was diagnosed if the total AHI was
10 events per hour and if at least 50% of events were obstructive and/or mixed, whereas central SDB was diagnosed when at least 50% of events were central. Significant SDB was arbitrarily defined as an AHI of
20 events per hour of sleep as the prevalence of SDB increases with age,25
and older patients with > 20 obstructive respiratory events per hour of sleep have been reported to have shorter survival times than those with minimal SDB.26
Our study was approved by the Ethics Committee of the Chinese University of Hong Kong, and appropriate informed consent was obtained from the subjects.
Following the polysomnography, each patient was interviewed by the respiratory physician on duty. Those with AHIs of
10 events per hour were offered a trial of nasal CPAP treatment, as it is generally recommended that patients with documented vascular diseases (in this case, ischemic stroke) be treated at a lower threshold.27
Our nurse would select and fit a comfortable CPAP mask from a wide range of choices for the patient, who would then be given a short trial of CPAP therapy (AutoSet; Resmed; Sydney, Australia) for approximately 30 min for acclimatization in the afternoon. Attended CPAP titration was performed with the CPAP auto-titrating device (AutoSet) on the second night of the study in our hospital. Several studies28
29
have shown that automatic CPAP titration is as effective as manual titration in correcting the obstructive respiratory events, in arousal frequency, and in improving oxygenation. Throughout the night and the next morning, the nurses on duty would deal with any discomfort related to the CPAP treatment. The CPAP pressure for each patient was set at the minimum pressure needed to abolish snoring, obstructive respiratory events, and airflow limitation for 95% of the night, as determined by the overnight CPAP titration study. All the patients were prescribed the use of a CPAP device (Aria LX CPAP device; Respironics Inc; Murrysville, PA), which automatically turned on when the patients breathed into the mask and shut off when the mask was removed. The CPAP device (Aria LX) contains a microprocessor that records the time spent at effective pressure (measured by a mask pressure transducer recorder).
We have adopted the following terminology as suggested by Grunstein and Sullivan30 describing patients interaction with CPAP: acceptance refers to the proportion of patients who meet selection criteria for CPAP treatment and actually proceed to have their pressure level determined; prescription refers to the proportion of patients who accept CPAP and commence home treatment; adherence refers to the proportion of patients who are prescribed CPAP and report that they are continuing to use CPAP; and usage refers to the proportion of patients with machines switched on for more than an arbitrary period of time. For the purpose of this study, we measured objective compliance by the mean rate of CPAP use (hours per day), as reflected by the effective mask pressure time.
In addition to repeating polysomnography for patients who were prescribed nasal CPAP treatment, other patients with baseline AHI values of
10 events per hour who were not receiving CPAP treatment were invited to return for reassessment with the ESS and progress polysomnography at 1 month to look for any spontaneous improvement. For those patients who had commenced nasal CPAP treatment after the baseline polysomnography, objective CPAP compliance (ie, effective mask pressure) for > 3 months was assessed by examining the data downloaded from the software of the CPAP device.
Statistical Analysis
All data were presented as the mean ± SD unless otherwise stated. Nominal data were analyzed with the
2 test. An unpaired t test was used for continuous data. For comparison between the patients and the control subjects, and between patients with an AHI of
20 and those with AHI of < 20 events per hour, an unpaired t test was used for normally distributed variables and a Mann-Whitney U test was used for non-normally distributed variables. Statistical significance was set at p < 0.05. Data analysis was performed with a commercially available statistical analysis software package (SPSS, version 10.0 for Windows; SPSS Inc; Chicago, IL).
| Results |
|---|
|
|
|---|
Stroke Assessment
All of our patients were admitted to the hospital within 4 days of the onset of symptoms. The sites of ischemic stroke determined according to the Bamford classification19
were as follows: partial anterior circulation, 15 patients (29.4%); total anterior circulation, 5 patients (9.8%); lacunar, 26 patients (51%); and posterior circulation, 5 patients (9.8%). The mean BI was 14.3 ± 4.5, and the mean NIH stroke score was 3.8 ± 3.6.
Sleep Assessment
From the SHQ, 27 patients (53%) reported a history of snoring and 24 patients (47%) reported a history of daytime sleepiness, while only 1 patient had history of witnessed apnea prior to experiencing the ischemic stroke (Table 1
).
|
10 events per hour was 34 (67%), those with an AHI of
15 events per hour was 31 (61%), the number with an AHI of
20 events per hour was 25 (49%), and the number with an AHI of
30 events per hour was 16 (31%). Of the 34 patients with a total AHI of
10 events per hour, the mean AHI was 31.9 ± 15.9 events per hour, the mean obstructive AHI was 27.4 ± 15.1 events per hour, and the central AI was 3.7 ± 6.3 events per hour, and, by definition, they all had the obstructive type of SDB. The characteristics of the control group (17 men and 8 women) were similar to the patients with ischemic stroke, but the frequency of significant obstructive SDB was lower in the control group (Table 2
).
|
20 events per hour vs those with an AHI of < 20 events per hour. A higher BMI was the only factor associated with those with significant SDB, who had a lower minimum SpO2 (Table 3
). The site of the stroke (Bamford classification), the severity of the stroke (NIH scale), and functional status (BI) were found not to be associated with the severity of SDB.
|
10 events per hour were given a 30-min trial of nasal CPAP (AutoSet) at 4 cm H2O for acclimatization in the afternoon. However, 14 patients refused to take part in the overnight CPAP titration study, and 4 patients could not tolerate the overnight study, while CPAP titration was successfully performed in 16 patients (47%) with a mean CPAP level of 10.8 ± 1.4 cm H2O.
Only 4 of the 16 patients proceeded to home CPAP treatment. The SHQ revealed that all four patients were snorers (mild, two patients; moderate, one patient; and severe, one patient) and that three patients had moderate-to-severe daytime sleepiness. The baseline sleep study of these four patients revealed mean a BMI of 30.8 ± 4.7 kg/m2, a neck circumference of 43.0 ± 1.3 cm, an AHI of 32 ± 21 events per hour, a minimum SpO2 of 94 ± 2%, an ESS of 10.3 ± 2.6, and a CPAP level of 12.3 ± 1.6 cm H2O. At 1 month, the mean AHI was 34 ± 16 events per hour, also of a predominantly obstructive type (p = 0.47 compared to baseline AHI), while the mean ESS of the four patients was 9.3 ± 7.4 at 1 month and 8.5 ± 5.1 at 3 months. The objective CPAP compliance at > 3 months, as measured by the CPAP device monitor, was 2.5 ± 0.6 h per night, and the percentage of nights with CPAP usage of
4 h per night was 30 ± 9%.
Follow-up Sleep Study for Those Not Prescribed Nasal CPAP
We had also invited patients with baseline AHI values of
10 events per hour who had not been prescribed CPAP (n = 30) to return for repeat polysomnography at 1 month to look for any spontaneous improvement, but only 20 patients agreed to be readmitted to the hospital for this purpose. The mean age of the subgroup was 65.3 ± 11.9 years, the mean BMI was 26.2 ± 4.1 kg/m2, the mean neck circumference was 38.4 ± 3.5 cm, and the mean ESS was 7.0 ± 3.7. The severity of obstructive SDB improved over 1 month with fewer patients having significant SDB. There was a trend toward improvement for the obstructive respiratory events, but no significant change was noted for the central events at 1 month (Table 4
).
|
| Discussion |
|---|
|
|
|---|
20 events per hour of sleep, among our patients following a first-ever ischemic stroke in the acute phase compared to the control group (49% vs 24%, respectively; p = 0.04). The prevalence of snoring prior to stroke was 53%, while 55% of our patients experienced hypertension. Daytime sleepiness was reported by 47% of patients and was graded as severe in 17.6%. There were fewer patients with significant obstructive SDB in the rehabilitation phase at 1 month in the subgroup of 20 patients compared to baseline (45% vs 80%, respectively; p = 0.02). Despite lowering the treatment threshold to an AHI of
10 events per hour, the acceptance rate for nasal CPAP was only 47%. The objective compliance for > 3 months was dismally low at 2.5 h per day for the four patients who were prescribed nasal CPAP treatment, with only 30% of nights with CPAP usage of
4 h per night.
Several clinical studies, which are briefly summarized in Table 5 , have reported a high prevalence of obstructive SDB in stroke patients in the acute phase11
12
13
15
and in the rehabilitation phase.10
14
15
Some of these studies were limited by a relatively small sample size,10
11
12
a lack of a control group,12
14
15
or mixing of a heterogeneous group of patients with transient ischemic attack, ischemic stroke, and hemorrhagic stroke.10
11
13
14
15
Nevertheless, in comparison with different populations of patients who had experienced postischemic stroke in whom SDB was defined as either an AHI of either
10 or
20 events per hour, our results are in agreement with other studies that there is an unexpectedly higher prevalence of obstructive SDB among the stroke victims than among the age-matched control groups10
11
13
or with the results of other epidemiologic studies of the older age group.25
26
The BMI of our ischemic stroke patients with significant SDB was lower than the BMI of other Western populations. Nevertheless, a higher BMI was the only factor associated with significant SDB in our study, whereas, as also experienced by Parra et al,15
the stroke site, stroke severity, and functional status were not. Bassetti and Aldrich,13
however, have found a higher frequency of SDB in older patients with higher BMIs and more severe strokes. The partial spontaneous improvement of obstructive SDB at the follow-up polysomnography at 1 month among our subgroup of 20 ischemic stroke patients with a baseline AHI of
10 events per hour suggests that preexisting SDB may have been worsened transiently by the acute cerebral ischemic event. In contrast, Parra et al15
have noted, in their 23 patients with transient ischemic attack and 59 patients with ischemic stroke, an improvement in central events at 3 months, while the obstructive component remained largely unchanged.
|
In addition to hypertension, other potential mechanisms linking SDB and ischemic stroke include increased platelet activation, aggregation with possible effects of adrenergic stimulation on platelet function, and reduced fibrinolytic activity in patients with OSAS.37 38 39 40 Interestingly ischemic stroke often occurs during sleep or the early morning hours,41 42 and platelets from healthy subjects have shown enhanced ability to aggregate between 6 AM and 9 AM.43
Changes in cerebral blood flow (CBF) have been reported during and after episodes of obstructive sleep apnea (OSA). In patients with OSAS, reduced regional CBF, especially in the brainstem and cerebellum during non-rapid eye movement sleep, has been noted during wakefulness compared to healthy subjects.44 A marked increase in intracranial pressure and a decrease in cerebral perfusion have been observed during OSAS.45 Fischer et al46 have detected, with transcranial Doppler ultrasonography, a 15% and 20% reduction, respectively, in the mean and systolic CBF velocities of the middle cerebral artery during sleep in patients with OSAS, while Netzer et al47 found a > 50% decrease in CBF in patients with OSAS compared to those with central apnea. A study48 using near-infrared spectroscopy has shown cerebral oxygen desaturation associated with cerebral hypoperfusion during episodes of OSA. An initial increase of 15% in CBF velocity immediately after termination of the OSA episode, followed by a 23% reduction with reference to baseline values, was observed by Balfors and Franklin,49 suggesting some impairment of vasodilator reserve.
There are several favorable, hemodynamic effects of nasal CPAP on the cardiovascular system on patients with OSAS. The impairment in cerebral autoregulation can be corrected by nasal CPAP therapy.50 Sympathetic nerve activity in patients with OSAS can be reduced by CPAP treatment.51 52 Plasma levels of nitric oxide, a powerful vasodilator that is released from the endothelium, have been shown to be decreased in OSAS patients but can be promptly reversed by nasal CPAP treatment.53 54 Effective treatment of OSAS with nasal CPAP can reduce platelet activation, aggregation,38 and morning fibrinogen levels in patients with OSAS without stroke.55 A recent randomized, oral placebo controlled study56 has shown that CPAP therapy over a period of 4 weeks can reduce BP in patients with OSAS, particularly in those who experience frequent episodes of nocturnal hypoxemia with 5-mm Hg drops in diastolic BP. The same degree of reduction in diastolic BP, achieved with antihypertensive medications, was associated with 42% and 31% decreases, respectively, in stroke over > 5 and 10 years.57 58
There is robust evidence showing significant improvement of symptoms, quality of life, and daytime function in patients treated with nasal CPAP.59 60 61 Our previous study18 on newly diagnosed OSAS patients who had not experienced strokes has shown full CPAP acceptance and a high objective compliance, and a high baseline AHI was the only significant independent predictor of better CPAP compliance. Others have found a positive correlation between the ESS scores,62 63 BMI,64 and CPAP compliance. The mean ESS scores among our 51 patients with ischemic stroke and those with significant SDB were 6.8 ± 3.6 and 7.3 ± 3.7, respectively, and there was no significant difference compared to the control group. Although the sample size was too small for meaningful statistical analysis, the four patients who were prescribed nasal CPAP had features of more classic OSAS with a higher mean baseline ESS score (10.3 ± 2.6), BMI (30.8 ± 4.7), and neck circumference (43.0 ± 1.3 cm), and more prominent symptoms such as snoring and daytime sleepiness prior to stroke than those not accepting CPAP. These four patients most likely had OSAS before they experienced ischemic stroke, and this would also explain the lack of improvement in AHI in the follow-up polysomnography and their acceptance of nasal CPAP. The mean ESS scores in healthy subjects vs OSAS patients in a local study65 were found to be 7.5 ± 3.0 and 13.2 ± 4.7, respectively. The mean ESS scores reported by other studies of patients with stroke10 11 12 13 14 15 were essentially within the normal range (Table 5) .
As our acute stroke patients presented mainly with motor deficits rather than daytime sleepiness, it was perhaps not surprising that CPAP acceptance and compliance were both low. Although the ESS score may not reflect objective measures of sleepiness,66 it has been reported to be more discriminating than the Maintenance of Wakefulness Test and the Multiple Sleep Latency Test67 as a test of daytime sleepiness. Another possible reason for poor CPAP acceptance might be related to partial spontaneous improvement of SDB, which we have observed in our patients over a period of 4 weeks after the acute cerebral ischemic event. Nevertheless, a recent study68 conducted in the rehabilitation setting (mean ESS score, 7.2) has reported improvement in subjective well-being and a reduction in mean nocturnal BP following 10 days of CPAP treatment, while 70.5% of their subjects with ischemic or hemorrhagic stroke indicated, prior to hospital discharge, that they would adhere to CPAP treatment at home. Another study69 of a heterogeneous group of ischemic and hemorrhagic stroke patients with SDB has shown improvement of depressive symptoms with CPAP treatment in the rehabilitation phase, although only 50% of the subjects in that study were receiving CPAP therapy for > 4 h per night, with lower usage in those with delirium and severe cognitive impairment.
There were several limitations with this study. We excluded patients who were medically unstable, delirious, comatose, or noncommunicative, and, therefore, our results might not reflect the prevalence of SDB in the severe end of the spectrum of ischemic stroke. To demonstrate whether SDB was an independent risk factor for stroke, a larger sample size with a control group, matched for age, sex, BMI, and other cardiovascular risk factors, would have been required.
In summary, this study has shown a high prevalence of obstructive SDB in patients with ischemic stroke in the acute phase. A higher BMI is the only factor associated with significant SDB. In many cases, SDB in patients who have experienced acute stroke is different from classic OSAS, and this is reflected by the lack of significant sleepiness, poor CPAP acceptance, and partial spontaneous improvement at 1 month. Further studies are needed to assess which subset of stroke patients with SDB will benefit from CPAP, how to improve CPAP acceptance and compliance, and whether the early diagnosis and treatment of SDB will improve morbidity, mortality, and quality of life in such patients.
| Acknowledgements |
|---|
| Footnotes |
|---|
This project was funded by Chinese University of Hong Kong direct grant No. 2084008.
Received for publication August 23, 2001. Accepted for publication March 1, 2002.
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
D. S. Hui, F. W. Ko, J. P. Fok, M. C. Chan, T. S. Li, B. Tomlinson, and G. Cheng The Effects of Nasal Continuous Positive Airway Pressure on Platelet Activation in Obstructive Sleep Apnea Syndrome Chest, May 1, 2004; 125(5): 1768 - 1775. [Abstract] [Full Text] [PDF] |
||||
![]() |
G J Gibson Sleep disordered breathing and the outcome of stroke Thorax, May 1, 2004; 59(5): 361 - 363. [Full Text] [PDF] |
||||
![]() |
P M Turkington, V Allgar, J Bamford, P Wanklyn, and M W Elliott Effect of upper airway obstruction in acute stroke on functional outcome at 6 months Thorax, May 1, 2004; 59(5): 367 - 371. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||