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Volume 15 No. 06
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Effect of CPAP Treatment of Sleep Apnea on Clinical Prognosis After Ischemic Stroke: An Observational Study

José Haba-Rubio, MD1; Jelena Vujica, MD1; Yannick Franc, MSc2; Patrik Michel, MD3; Raphaël Heinzer, MD, MPH1
1Center for Investigation and Research in Sleep (CIRS), Lausanne University Hospital (CHUV), Lausanne, Switzerland; 2Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland; 3Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), Lausanne, Switzerland

ABSTRACT

Study Objectives:

To evaluate continuous positive airway pressure (CPAP) treatment in patients with moderate to severe sleep-disordered breathing (SDB) after an ischemic stroke.

Methods:

We identified patients included in the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) who underwent polysomnography after an ischemic stroke. We compared patients without significant SDB (apnea-hypopnea index [AHI] < 15 events/h: SDB−), with AHI ≥ 15 events/h who refused CPAP or with poor CPAP adherence (SDB+ CPAP−), and patients with SDB effectively treated by CPAP (SDB+ CPAP+).

Results:

We analyzed data from 101 patients (age 68.5 ± 11.1 years, 84.1% men). In multivariate analysis the SDB+ CPAP+ group was associated with a significant reduction of stroke recurrence and mortality (odds ratio 0.13, 95% confidence interval 0.00–0.86, P = .031), whereas atrial fibrillation was independently associated with a higher risk (odds ratio 4.32, 95% confidence interval 1.51–12.33, P = .006). Event-free survival analysis (stroke recurrence and death) after 2-year follow-up showed that those in the SDB+ CPAP+ group had significantly higher cardiovascular survival, and Cox proportion hazard model identified CPAP treatment as significantly associated with survival time (P = .025). The AHI and the National Institutes of Health Stroke Scale subacute score were independently associated with CPAP adherence among patients with SDB.

Conclusions:

This observational study shows that CPAP treatment in stroke patients with moderate to severe SDB is associated with lower rates of stroke recurrence and death.

Citation:

Haba-Rubio J, Vujica J, Franc Y, Michel P, Heinzer R. Effect of CPAP treatment of sleep apnea on clinical prognosis after ischemic stroke: an observational study. J Clin Sleep Med. 2019;15(6):839–847.


BRIEF SUMMARY

Current Knowledge/Study Rationale: Sleep-disordered breathing (SDB) is recognized as a cerebrovascular risk factor, but it is not completely established whether its treatment improves prognosis after stroke. The aim of our study was to determine the effect of continuous positive airway pressure (CPAP) treatment for SDB on clinical outcomes in patients with ischemic stroke.

Study Impact: Our study shows that adequate CPAP treatment in patients who have had a stroke with moderate to severe SDB is associated with lower rates of stroke recurrence and death. However, adherence in this population is low.

INTRODUCTION

Sleep-disordered breathing (SDB) is highly prevalent in the general population,1 and particularly after stroke. In a meta-analysis of 2,343 patients who had an ischemic or hemorrhagic stroke and transient ischemic attack (TIA), the prevalence of SDB—defined by an apnea-hypopnea index (AHI) > 5 events/h—was 72% and the rate of moderate to severe SDB (AHI > 20 events/h) was 38%.2 SDB was most severe in the acute phase of stroke, tended to improve during recovery, and was mainly of obstructive type.2 SDB was similarly prevalent in stroke and TIA, indicating that SDB precedes stroke and it is not, in most cases, a consequence of brain damage.2

SDB is recognized as a cardiovascular risk factor and has been associated with incident stroke.3 Different mechanisms could be involved in the increased risk of stroke in patients with SDB, including intermittent hypoxemia, sympathetic activation, CO2 retention, intrathoracic pressure changes, endothelial dysfunction, increased platelet activation, systemic inflammation, and its association with hypertension, diabetes, metabolic syndrome, and cardiac arrhythmias.1,4 SDB is also associated with poor stroke outcomes and a negative predictor of all-cause mortality and recurrent vascular events following stroke.5

Continuous positive airway pressure (CPAP) is the treatment of choice for SDB. Although it is well established that CPAP improves SDB-related symptoms, as excessive daytime sleepiness and cognitive dysfunction,6 it is not completely clear whether it improves cardiovascular consequences of SDB,7 and even though the American Heart Association recommends considering CPAP treatment for patients with ischemic stroke or TIA and SDB,8 only a limited number of studies have examined the effect and determinants of CPAP in improving post-stroke outcomes.9,10 Some of these studies reported favorable effects on stroke recovery, recurrent vascular events and cardiovascular survival.1113 However, in other studies CPAP treatment did not influence neurologic outcomes nor recurrent vascular events.1416

The aim of our study was to determine the effect of CPAP treatment for SDB on clinical outcomes (including functional recovery, risk of recurrent stroke and death) in patients with ischemic stroke. In this observational study, we further sought to determine the CPAP adherence and its determinants in patients with stroke and SDB.

METHODS

Participants

We identified patients included in the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) between January 2010 and September 2014, who underwent polysomnography (PSG) at the Center for Investigation and Research on Sleep (CIRS), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University Hospital, Switzerland, for suspected SDB.17 Briefly, and as previously described, ASTRAL prospectively collects epidemiological, clinical, laboratory, and multimodal brain imaging data from all patients with acute (within 24 hours of symptom onset) ischemic stroke admitted to the CHUV. Patients' workup included: complete physical and neurological evaluation; laboratory measurements; assessment of cardiovascular risk factors; brain parenchymal imaging (computed tomography [CT] or magnetic resonance imaging); arterial imaging (CT angiography, magnetic resonance angiography, carotid and transcranial Doppler studies, or conventional angiography); the National Institutes of Health Stroke Scale (NIHSS) score (used to objectively assess the impairment caused by stroke [scores ranging from 0 no stroke symptoms to 42 severe stroke] on admission and after 7 days18; and the modified Rankin scale score before the stroke19 to assess functional outcome (scores ranging from 0 no symptoms to 6 death). Stroke subtype was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification,20 modified for cardiac sources according to the SSS-TOAST algorithm.21 ASTRAL was approved by the Ethics Committee of the University of Lausanne. The decision to perform PSG following hospitalization was made by the physician/neurologist in charge of the patient using a three-step protocol: (1) STOP-BANG screening score, if positive; (2) an Apnealink (ResMed, San Diego, California, United States) (nasal pressure and oximetry) polygraphy was performed, if respiratory event index > 10 events/h; (3) PSG was organized.22

Polysomnography

Full overnight sleep recordings took place at the CIRS in the weeks following hospitalization for the stroke using Embla PSG acquisition system (Embla Flaga, Reykjavik, Iceland), and included a total of 16 channels, in accordance with 2007 American Academy of Sleep Medicine (AASM) recommended setup specifications23: four electroencephalogram (EEG) electrodes (F1, F2, O1, and O2), two electrooculogram electrodes (EOG; one to each outer cantus), two surface electromyogram (EMG) electrodes placed over submental muscles; EEG and EOG electrodes referenced to the linked earlobes (A1 + A2). Chest and abdominal movements, nasal air pressure (to assess nasal airflow), and body position were simultaneously recorded. Oxyhemoglobin saturation was recorded using a Nonin pulse oximeter (Nonin Medical, Inc., Plymouth, Minnesota, United States) using a sampling frequency of 10 Hz. Leg movements were recorded using surface EMG (for right and left anterior tibialis muscles). All PSG recordings were visually scored by qualified sleep technicians using Somnologica software (version 5.1.1, Embla Flaga) and reviewed by a trained sleep physician (JHR). Sleep stages were scored in 30-second epochs according to the 2007 AASM criteria.23 Respiratory events were scored according to the 2012 AASM criteria.24 Hypopneas were scored if > 30% reduction in the airflow signal associated with either an arousal or a ≥ 3% oxygen desaturation. The average number of apneas and hypopneas per hour of sleep (AHI) was calculated. Daytime sleepiness at the time of the PSG was assessed with the Epworth Sleepiness Scale.25

Follow-Up

After hospital discharge, all patients were followed by a neurologist at the CHUV outpatient stroke clinic at 3 and 12 months after stroke or were contacted by phone by medical personnel to evaluate patient's handicap. At each visit, a physical and neurological examination was performed and modified Rankin scale (mRankin) was administered. In case of a suspected recurrent cerebrovascular event, confirmation was sought from the treating general physician or hospital. When a patient died during the follow-up period, the cause of death was recorded according to medical records and the death certificate. Stroke recurrence and mortality during the 24 months following the stroke were recorded during subsequent visits or through telephone contact with the patient or with the treating general physician.

A CPAP treatment regimen (auto-CPAP, 4–14 cmH2O) was offered to all patients with AHI > 15 events/h if predominantly obstructive.

As part of our clinical procedures, patients who accepted the treatment were regularly monitored for CPAP treatment at the CIRS by sleep specialists and a dedicated health provider (Ligue Pulmonaire Vaudoise). The first visit was scheduled 2 to 3 weeks after CPAP introduction, then at 3 months, 6 months, and 1 year, and at least once a year thereafter. Additional visits were scheduled if the patient had difficulties with the mask or the CPAP device, or changes in somnological symptomatology were detected. CPAP adherence and other information was assessed by memory card that recorded mask-on time. CPAP follow-up monitoring included the percentage of days of use and the number of hours of use per night as well as the residual AHI provided by the machine. Adequate adherence with CPAP was defined as use > 4 h/night > 70% of nights, generally admitted as a clinical and empirical standard of CPAP adherence.26

We categorized the patients into different groups according to the presence of a significant SDB at the PSG, and according to the treatment adherence at 1 year:

  1. SDB−: patients with suspected SDB during poststroke hospitalization, but whose diagnosis was excluded after PSG (AHI < 15 events/h).

  2. SDB+ CPAP−: patients with SDB (AHI > 15 events/h at the PSG) who refused CPAP treatment or patients with SDB (AHI > 15 events/h at the PSG) who accepted CPAP treatment but who showed poor adherence (objective use < 4 h/night, < 70% of nights)

  3. SDB+ CPAP+: patients with SDB (AHI > 15 events/h at the PSG) who accepted CPAP therapy and were adherent (objective use > 4 h/night, > 70% of nights)

Patients who had already been treated for SDB prior to the stroke CIRS were excluded from the analysis. We determined adherence at 1 year, but patients who were adherent at 1 year were already adherent at 3 months, suggesting that the adherent/nonadherent profile appeared very early (there was no switch between adherent/nonadherent groups between 3 months and 1 year).

Statistical Analyses

Demographic and clinical characteristics of the patients included in the study were analyzed using parametric or non-parametric statistics where appropriate. Categorical variables are presented as number and proportion, whereas the quantitative variables are presented with mean and standard deviation (SD). Univariate comparisons between the groups were carried out using the χ2 test, Fisher exact test, t test, or Wilcoxon rank-sum test. We used a logistic regression to determine the factors associated with good therapeutic adherence to CPAP. Survival analysis of cerebrovascular events and death were performed, using Kaplan-Meier tests. Finally, a Cox model was used to investigate the effect of the presence of SDB and the effect of CPAP treatment in terms of recurrence of stroke and death, adjusting for prognostic covariates. The threshold of statistical significance was set at P < .05. Statistical analyses were performed using Stata (version 11, StataCorp, College Station, Texas, United States) and MedCalc for Windows (version 19.03, MedCalc Software, Ostend, Belgium).

RESULTS

General Characteristics

During the observation period, we identified in the ASTRAL database 114 patients who had undergone PSG. Of these, 13 were excluded from the study because the PSG preceded the stroke (n = 10), they received oxygen therapy at home (n = 1) or they lived abroad and it was not possible to have access to the follow-up data (n = 2). The remaining 101 patients constitute the study population. The mean delay between the stroke and the PSG was 98 days, with a range between 29 and 158 days and no significant differences between the three groups. The Epworth Sleepiness Scale score was similar between groups at the time of the PSG. Of the 101 patients studied, 25 had no significant SDB and no CPAP treatment was offered (SDB− group). For the remaining 76 who had SDB, CPAP treatment was recommended. Respiratory events were predominantly obstructive, and no patients met the criteria for central apnea syndrome. Among these 38 patients, 50% refused treatment or did not tolerate an initial therapeutic trial (SDB+ CPAP− group). Ten patients (13.1%) accepted CPAP treatment, but adherence at 6 and 12 months was considered insufficient (SDB+ CPAP− group). Finally, 28 patients (36.8%) were treated effectively with CPAP for SDB (SDB+ CPAP+ group) (Figure 1). The mean AHI in the SDB− group was 9.7 ± 6 events/h. The other two groups with SDB had a mean AHI of 37.7 ± 23.6 events/h in the SDB+ CPAP− group and 47.7 ± 29.1 events/h in the SDB+ CPAP+ group (P = .105). Treatment with CPAP was started 130.4 ± 35.7 days after the onset of stroke in SDB+ CPAP+ group. The percent of nights CPAP was used in this group at the 2-year follow-up visit was 91.6 ± 11.8% and the mean duration of CPAP use was 6.27 ± 1.17 h/night. The mean residual AHI was 3.11 ± 5.31 events/h.

Study population.

CPAP = continuous positive airway pressure, PSG = polysomnography, SDB = sleep-disordered breathing.

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Figure 1

Study population.

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Overall, the studied population displayed the typical characteristics of a clinical stroke population, with a mean age older than 60 years (68.5 ± 11.1 years), a male preponderance (84.1%), a high prevalence of cardiovascular risk factors, and comorbid heart conditions. Most strokes were of minor severity (NIHSS score ≤ 4 in 53.5% of patients), and cardioembolic stroke or undetermined etiology were the most frequent types of stroke (Table 1).

Demographic, clinical, and polysomnographic characteristics of the studied population.

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Table 1

Demographic, clinical, and polysomnographic characteristics of the studied population.

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Baseline characteristics of the three groups were similar in terms of age and sex distribution. Patients in the SDB+ CPAP+ group had a higher body mass index (BMI) than patients in the SDB− group (29.5 ± 3.9 versus 27.1 ± 4.3, P = .049). No major differences were found for cardiovascular risk factors prevalence between groups. The etiology of the stroke in the SDB+ CPAP− group was more frequently considered to be cardioembolic when compared with the SDB− group, and patients in the SDB+ CPAP+ group had more atherosclerotic strokes than patients in the SDB− group. Overall, there were no significant differences in the severity of stroke, evaluated by the NIHSS score on admission, and groups were similar in terms of mRankin score before the stroke, the percentage of patients with significant handicap and in the frequency of hemorrhagic transformation (Table 1). The groups were balanced in terms of acute intervention (intravenous thrombolysis or endovascular treatment done or attempted) in the hospital acute phase or the arterial territory concerned (anterior versus posterior circulation) (results not shown).

CPAP Adherence

We used a logistic regression model to determine factors associated with good adherence to CPAP treatment, comparing patients in the SDB+ CPAP− and SDB+ CPAP+ groups, including age, sex, Epworth Sleepiness Scale score at the time of the PSG, AHI, 3-month mRankin score, and NIHSS score at admission and at 7 days (Table 2). The severity of SDB measured by the AHI was independently associated with good CPAP adherence (odds ratio [95% confidence interval (CI)] 1.03 [1.00–1.06], P = .03). Higher NIHSS scores at 7-day highs (reflecting worst stroke disability) were associated with lower adherence to CPAP (0.78 [0.59–0.96], P = .01).

Determinants of good CPAP adherence (CPAP use > 4 h/night, > 70% nights).

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Table 2

Determinants of good CPAP adherence (CPAP use > 4 h/night, > 70% nights).

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Effect of CPAP Treatment on Functional Outcome

At 12 months, the percentage of patients with a “good outcome” (mRankin score 0–2) was significantly higher in the CPAP-treated group (96.4% versus 79.2%, P = .046). The global mRankin score showed a trend to be more favorable in the SDB+ CPAP+ group compared to the SDB+ CPAP− group (0.89 ± 0.83 versus 1.46 ± 1.44, P = .058). However, the difference between the mRankin score before the stroke and at 12 months after the stroke was not significantly different between groups (Table 1).

Outcome in Terms of New Cerebrovascular Events (TIA/Stroke Recurrence) and Mortality

In the SDB− group, 1 patient (4%) experienced a new cerebrovascular event at the 24-month follow-up. The cardiovascular mortality rate was zero in this group. In the SDB+ CPAP− group, 5 patients experienced a total of 6 (12.5%) new cerebrovascular events (1 patient had two stroke recurrences during the follow-up period), and 4 (8.3%) died of cardiovascular cause during the observational period. Finally, in the SDB+ CPAP+ group, the stroke recurrence and the mortality rates were zero. Univariate comparisons of cerebrovascular events and mortality between the groups was statistically significant (χ2 = 8.84, P = .012).

In the multivariable analysis of factors associated with a higher risk of stroke recurrence and mortality, age, sex, BMI, dyslipidemia, hypertension, diabetes, and smoking were not independently associated with a higher risk of cerebrovascular recurrence and mortality at follow-up. However, the presence of atrial fibrillation was associated with increased risk (odds ratio [95% CI] 4.32 [1.51–12.33], P = .006), and the use of CPAP with a significant reduction in risk (0.13 [0–0.86], P = .031) (Table 3).

Factors associated with stroke recurrence and mortality at follow-up (24 months).

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Table 3

Factors associated with stroke recurrence and mortality at follow-up (24 months).

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The median follow-up time for survival was 199 days (interquartile range 107–408). Cox proportion hazard model including as variables: age, sex, BMI, atrial fibrillation (yes/ no), hypertension (yes/no), dyslipidemia (yes/no), diabetes (yes/no), smoking (yes/no) and CPAP use (yes/no), showed that CPAP treatment was significantly associated with survival time (cerebrovascular event recurrence + death), after 24 months (P = .025) (Figure 2).

Event-free survival (TIA/stroke recurrence and mortality) in SDB−, SDB+ CPAP−, and SDB+ CPAP+ groups.

CPAP = continuous positive airway pressure, SDB = sleep-disordered breathing, TIA = transient ischemic attack.

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Figure 2

Event-free survival (TIA/stroke recurrence and mortality) in SDB−, SDB+ CPAP−, and SDB+ CPAP+ groups.

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DISCUSSION

In this study we aimed to evaluate in real-life conditions the effect of CPAP treatment in patients with an ischemic stroke and moderate to severe SDB diagnosed by PSG after the acute phase. The most significant finding of our study is that patients with SDB treated with CPAP after an ischemic stroke have fewer cerebrovascular recurrences and lower cardiovascular mortality rate at follow-up.

Indeed, in the multivariable model, the absence of use of CPAP, along with the presence of atrial fibrillation, were the only independent factors associated with higher risk of recurrence/death. CPAP treatment was also associated with a higher percentage of patients with a favorable outcome (measured with the mRankin score) 1 year after the stroke, but the difference between the mRankin before the stroke and the mRankin at 12 months after the stroke was not significantly different between groups. However, the overall adherence of CPAP treatment after stroke was poor, as only 36.8% of those patients with SDB (AHI > 15 events/h) had good adherence at long-term follow-up. Nevertheless, one must keep in mind that this is an observational and not a randomized study. Observational studies can introduce major bias in the interpretation of results, and they also reflect real-life conditions.

SDB is a well-documented risk factor for incident cardiovascular disease and mortality, as it has been revealed by data generated from long-term prospective observational cohort studies.2729 Specifically the risk of stroke has been evaluated in population-based studies28,3033 and SDB has been associated with increased risk of incident stroke.3

The treatment of choice for SDB is administration of CPAP during sleep. It has been proved that CPAP treatment significantly reduces sleepiness also improves quality of life in different domains in patients with SDB.34 Although treatment of SDB also seems to reduce systemic blood pressure35 and to improve cardiac function,36 no definite data show that CPAP prevents myocardial infarction, congestive heart failure, or stroke.37 In particular, the ability of CPAP to reduce recurrent cerebrovascular events and death after stroke is still under debate, due at least in part to small-scale groups and heterogeneous methodology in intervention studies.

Parra et al., in a prospective randomized controlled trial, assessed the effect of early CPAP treatment in patients with ischemic stroke and SDB defined by AHI ≥ 20 events/h.13,38 Patients were randomized to early CPAP (n = 71; treatment initiated 3 to 6 days after stroke onset) or conventional treatment (n = 69). The percentage of patients with neurological improvement 1 month after stroke was significantly higher in the CPAP group, and the mean time until the appearance of a cardiovascular event (including cardiac ischemic events, stroke recurrence, and cardiovascular mortality) was longer in the CPAP group. Patients in the CPAP group also had significantly higher cardiovascular survival than the control group, although cardiovascular event-free survival after 24 and 68 months was similar in both groups, despite a positive trend. Khot et al., in a pilot randomized, double-blind, sham-controlled trial after acute stroke, found a trend toward a benefit of active CPAP on recovery over sham in particular for cognitive outcomes.39

Bassetti et al. prospectively studied a consecutive series of patients admitted for acute ischemic stroke evaluated for SDB in the acute phase.40 CPAP treatment did not affect the outcome in patients with stroke and SDB, but only 8 of 70 patients with SDB adequately used the treatment on the long-term follow-up, leaving limited power to assess the association.

In their prospective observational study, Martinez-Garcia et al. found that patients with stroke and moderate to severe obstructive sleep apnea (AHI ≥ 20 events/h) who could not tolerate CPAP (n = 68) showed an increased incidence of cardiovascular events after a 7-year follow-up, especially new ischemic strokes with an odds ratio of 2.87 (95% CI 1.11–7.71), compared with patients who tolerated CPAP (n = 28), patients with mild disease (AHI 10–19 events/h; n = 36), and patients without SDB (AHI < 10 events/h; n = 31).41

Recent randomized controlled trials of CPAP treatment in patients with SDB with cardiovascular disease (patients with coronary artery disease7 and coronary or cerebrovascular disease42) failed to show an improvement in long-term adverse cardiovascular outcomes. However, post hoc analysis showed that the patients who were adherent to CPAP therapy had a significant lower risk of stroke in the follow-up.7,42

Adherence to treatment is thus a key point, and a significant limitation of CPAP therapy. This seems particularly true in patients with stroke, in whom overall adherence to CPAP therapy is very poor. In the current study, just over one-third of those in whom SDB was diagnosed were effectively treated during follow-up. These results are similar to those found by Bassetti et al.40 wherein fewer than 15% of all patients with stroke and SDB in the acute phase remained on CPAP treatment, and those found by Martinez-Garcia et al.41 wherein 29.2% were considered as having had good long-term adherence.

Many studies have identified factors that influence or predict CPAP adherence, including heavy snoring, severity of the disease, or excessive daytime sleepiness.43 In our study, the analysis of factors associated with good adherence showed that the severity of SDB measured by the AHI and the NIHSS score at 7 days after the stroke were independent determinants of long-term adherence to CPAP treatment, indicating that patients with more severe SDB are more prone to continue treatment in the long term. Neurological sequelae of stroke such as neglect or aphasia would also have an effect on adherence. Indeed, previous studies examining the use of CPAP in patients with stroke have identified factors such as the severity of motor disability and the presence of aphasia as associated with nonacceptance.44 In any case, there is a clear need to develop effective strategies to improve adherence in this population via education and intensive support, as well as evaluation of alternative treatments including mandibular advancement devices, positional therapy, surgery, and conservative measures (ie, weight loss), and development of new treatments.

Ultimately, the results of this study extend the scarce literature on this important topic by confirming the positive effect of CPAP therapy on long-term prognosis in patients with ischemic stroke and moderate to severe SBD. One of the major strengths of our study is that we used PSG, the gold standard to record sleep characteristics and SDB presence and severity, instead of limited channel portable respiratory recordings13,38 or an automatic CPAP device.40 Contrary to other previous studies, we did not perform the PSG and introduce treatment in the acute phase but in a more stable phase (around 3 months after the acute episode), eliminating the risk of treating patients with SDB that will spontaneously improve after the acute phase.40,45 In addition, treatment with CPAP in the acute phase is challenging, as patients are in a situation of high stress and may have neurological deficits (motor, cognitive). These factors could contribute to a prompt refusal of treatment. The time of PSG and the introduction of CPAP reflect our clinical practice in real-life conditions and can probably be extrapolated to other centers that follow similar procedures.

We acknowledge that this observational study is challenged by limitations that can influence the interpretation of the results. One of the major limitations is that this is not a randomized controlled trial and therefore bias may have been introduced, as patients adherent to CPAP treatment are probably also more adherent with pharmacological treatments, and more likely to adhere to health advisors' recommendations. Although there were no statistically significant differences between groups in terms of severity, it is possible that those adhering to CPAP had less disabling strokes and may have lower risk of cardiovascular mortality with lower burden of disease. In addition, only a limited number of patients were included, there were few events detected in our cohort, and larger studies are needed to confirm our results so that these results can be generalized to the entire stroke population. The decision to perform a PSG following hospitalization was driven by clinician based on suggestive symptomatology, STOP-BANG screening score, and Apnealink (nasal pressure and oximetry) polygraphy results, and this procedure may also be a source of selection bias. Early treatment of SBD from the first night after the stroke may produce better results, especially with regard to functional prognosis, by preserving the ischemic penumbra area of episodes of intermittent hypoxemia associated with the respiratory events, and more studies are needed to determine the optimal time to introduce the CPAP. Delay in CPAP after acute phase may be a missed opportunity to modify stroke recovery. We used as a criterion of good therapeutic adherence the historical benchmark of 4 h/night of CPAP use, on > 70% of nights, but it must be kept in mind that there is probably a treatment dose-effect as several studies have shown that more duration of CPAP use is associated with better outcomes.46

In conclusion, the current study including 101 patients with complete PSG after an ischemic stroke shows that good adherence to CPAP treatment in patients with moderate to severe SDB is associated with lower rates of recurrence and death at 2 years' follow-up. However, adherence in this population is very low, and efforts are needed to improve tolerance and acceptance of SDB treatment.

DISCLOSURE STATEMENT

All authors have seen and approve the final version of the manuscript. This study was supported by research grant from Vaud Pulmonary League (Ligue Pulmonaire Vaudoise). The authors report no conflicts of interest.

ABBREVIATIONS

AASM

American Academy of Sleep Medicine

AHI

apnea-hypopnea index

ASTRAL

Acute STroke Registry and Analysis of Lausanne

CPAP

continuous positive airway pressure

CT

computed tomography

EEG

electroencephalogram

EMG

electromyogram

EOG

electrooculogram electrodes

NIHSS

National Institutes of Health Stroke Scale

PSG

polysomnography

SDB

sleep-disordered breathing

TIA

transient ischemic attack

TOAST

Trial of ORG 10172 in Acute Stroke Treatment

ACKNOWLEDGMENTS

The authors thank the members of the Ligue Pulmonaire Vaudoise for their collaboration and financial support and all the patients who participated in this study.

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