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      Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery

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      , MD , , MD
      Neurology
      Lippincott Williams & Wilkins

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          Abstract

          Background:

          Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) are highly prevalent in stroke patients. Recent studies suggest that they represent both a risk factor and a consequence of stroke and affect stroke recovery, outcome, and recurrence.

          Methods:

          Review of literature.

          Results:

          Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in TIA and stroke patients are recommended in view of the very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of obstructive SDB with continuous positive airway pressure is recommended given the strength of the increasing evidence in support of a positive effect on outcome (Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB. Recently, both reduced and increased sleep duration, as well as hypersomnia, insomnia, and restless legs syndrome (RLS), were also suggested to increase stroke risk. Mainly experimental studies found that SWD may in addition impair neuroplasticity processes and functional stroke recovery. Treatment of SWD with hypnotics and sedative antidepressants (insomnia), activating antidepressants or stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias) are based on single case observations and should be used with caution.

          Conclusions:

          SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome. Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units.

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          Most cited references49

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          Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study.

          Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.
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            Association of sleep-disordered breathing and the occurrence of stroke.

            Sleep-disordered breathing has been linked to stroke in previous studies. However, these studies either used surrogate markers of sleep-disordered breathing or could not, due to cross-sectional design, address the temporal relationship between sleep-disordered breathing and stroke. To determine whether sleep-disordered breathing increases the risk for stroke. We performed cross-sectional and longitudinal analyses on 1,475 and 1,189 subjects, respectively, from the general population. Sleep-disordered breathing was defined by the apnea-hypopnea index (frequency of apneas and hypopneas per hour of sleep) obtained by attended polysomnography. The protocol, including polysomnography, risk factors for stroke, and a history of physician-diagnosed stroke, was repeated at 4-yr intervals. In the cross-sectional analysis, subjects with an apnea-hypopnea index of 20 or greater had increased odds for stroke (odds ratio, 4.33; 95% confidence interval, 1.32-14.24; p = 0.02) compared with those without sleep-disordered breathing (apnea-hypopnea index, <5) after adjustment for known confounding factors. In the prospective analysis, sleep-disordered breathing with an apnea-hypopnea index of 20 or greater was associated with an increased risk of suffering a first-ever stroke over the next 4 yr (unadjusted odds ratio, 4.31; 95% confidence interval, 1.31-14.15; p = 0.02). However, after adjustment for age, sex, and body mass index, the odds ratio was still elevated, but was no longer significant (3.08; 95% confidence interval, 0.74-12.81; p = 0.12). These data demonstrate a strong association between moderate to severe sleep-disordered breathing and prevalent stroke, independent of confounding factors. They also provide the first prospective evidence that sleep-disordered breathing precedes stroke and may contribute to the development of stroke.
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              Obstructive sleep apnoea and cardiovascular disease.

              Obstructive sleep apnoea (OSA) is a common health concern caused by repeated episodes of collapse of the upper airway during sleep. The events associated with OSA lead to brain arousal, intrathoracic pressure changes, and intermittent episodes of hypoxaemia and reoxygenation. These events activate pathways such as oxidative stress, sympathetic activation, inflammation, hypercoagulability, endothelial dysfunction, and metabolic dysregulation that predispose patients with OSA to hypertension and atherosclerosis. OSA is a common cause of systemic hypertension and should be suspected in hypertensive individuals, especially those with resistant hypertension. In patients with OSA, continuous positive airway pressure (CPAP) treatment reduces blood pressure, and its effects are related to compliance and baseline blood pressure. Evidence suggests that OSA is a risk factor for stroke and heart failure. An association between coronary heart disease and OSA seems to be limited to middle-aged men (30-70 years). Cardiac rhythm disorders occur in about half of patients with OSA, but their clinical relevance is still unknown. The association of OSA with cardiovascular risk is mainly based on studies in men, and an association has yet to be established in women. Data on older patients is similarly scarce. Currently, there is not enough evidence to support treatment with CPAP for primary or secondary prevention of cardiovascular disease. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Neurology
                Neurology
                neurology
                neur
                neurology
                NEUROLOGY
                Neurology
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0028-3878
                1526-632X
                27 September 2016
                27 September 2016
                : 87
                : 13
                : 1407-1416
                Affiliations
                From the Department of Neurology (D.M.H.), University Hospital Essen, Germany; and Department of Neurology (C.L.B.), University Hospital Berne, Switzerland.
                Author notes
                Correspondence to Prof. Dr. med. Hermann: dirk.hermann@ 123456uk-essen.de or Prof. Dr. med. Bassetti: claudio.bassetti@ 123456insel.ch

                Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the authors.

                Article
                NEUROLOGY2015714758
                10.1212/WNL.0000000000003037
                5047039
                27488603
                a5adba8f-e106-4d5f-9a85-448760983cab
                © 2016 American Academy of Neurology

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                : 27 December 2015
                : 09 June 2016
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