Sleep, diet, and exercise are the three core components of health and wellbeing. When sleep is disrupted, particularly over a long period of time, a chain of negative health effects takes place, including cardiovascular compromise. Sleep disorders and stroke can both occur by chance alone, but each may impact the other. Sleep apnea is the most common sleep disorder associated with stroke. Repeated disruptions in breathing during sleep are the hallmark of sleep apnea, and these events are associated with drop in oxygen saturation and swings in blood pressure. Sleep apnea is further differentiated into obstructive sleep apnea (OSA) and central sleep apnea (CSA), both of which have been reviewed by other articles in this series. Collectively, OSA and CSA in addition to sleep related hypoventilation, are referred to as sleep disordered breathing (SDB) or sleep apnea.

SDB is a prevalent but under diagnosed sleep disorder, with as many as 80% of patients going undiagnosed. The body of evidence linking SDB with stroke is growing; in particular, SDB is identified as an independent risk factor for morbidity in these individuals. SDB often affects patients before a stroke, but can also develop as a consequence of stroke. This article focuses on the existing and new data relating SDB and stroke, and concludes with practical practice strategies for identifying individuals with SDB.

Historical Aspect

It has only been since the early 1990's that sleep and stroke have been recognized as having a strong association, although there are several reports of changes in sleep and breathing in stroke patients, dating back to the 19th century. For example, John Cheyne recognized periodic breathing in cardiac disease in 1818.¹ Broadbent recognized sleep apnea symptoms with stroke in 1877.²

Epidemiology

Sleep Apnea is common after stroke. Over 20 studies were published between 1996 and 2010, and demonstrated that at least 50% of stroke patients also suffer from SDB, identified by an apnea/hypopnea index (AHI) of 10+/hr.³ These studies included almost 2,000 patients, and used polysomnography or respirography as the diagnostic method.

A 2010 meta-analysis of 29 published studies, including over 2,300 stroke patients, revealed that the frequency of sleep apnea with AHI < 5 have 72%, with AHI >20 was 38%, and that 7% of the sleep apnea was primarily central, vs. obstructive.⁴ These studies also showed that the type of stroke had no significant effect on the prevalence of SDB, yet patients with recurrent stroke had a higher percentage of SDB. Males were more affected than females (65% vs. 48% with AHI > 10).⁴

New Data

OSA is present in more than 50% of patients with stroke, and increases the risk of new-onset stroke, independent of obesity, hypertension, diabetes mellitus, dyslipidemia, and smoking.⁵

SDB, along with inflammatory changes, infection, and homocysteine, are all relatively newly identified risk factors for stroke, and may account for up to 50% of the cardiovascular disease risk.⁶ In particular, OSA may be a trigger for stroke and a novel target for stroke prevention. Martínez-García showed that CPAP can reduce the risk of recurrent stroke in patient who have had a stroke and have sleep apnea.⁷ Similarly SDB may increase the risk of atrial fibrillation which increases the risk of stroke (http://www.acc.org/latest-in-cardiology/articles/2014/07/18/15/43/sleep-disordered-breathing-and-afib).

Although this article focuses on SDB and stroke, it is notable to mention that recently, other sleep disorders, such as restless legs syndrome, circadian dysrhythmias, and primary insomnia have been identified as potential risk factors for vascular disease.^8,9,10

Clinical Features

Rather than displaying typical symptoms of SDB, patients with underlying cardiovascular disease may display a wide variety of symptoms. It is important to note that many patients do not report excessive daytime sleepiness and are not obese, both of which are the key clinical features of SDB.^11,12,13 The underlying brain damage may help explain the variety of symptoms associated with SDB. Nighttime symptoms may include³:

• difficulties falling asleep (sleep-onset insomnia)
• respiratory noises (snoring, stridor)
• irregular or periodic respiration
• apneas
• disrupted sleep with increased motor activity and frequent awakenings
• sudden awakenings with or without choking sensations
• shortness of breath
• palpitations and panic attacks
• orthopnea
• increased sweating
• Suppressed arousal responses due to severe hypoventilation (may cause death during sleep)

Daytime symptoms may include³:

• headaches
• fatigue
• excessive daytime sleepiness
• concentration and memory difficulties
• irritability
• depression
• breathing irregularities

Practice Strategies – from Therapy to Screening

SDB is detrimental to health and wellbeing and a proven contributor to morbidity in many stroke patients. The good news – SDB is treatable. Continuous positive airway pressure (CPAP) is the gold standard in treatment for people with mild, moderate, or severe SDB, and mandibular repositioning devices are a newer treatment option for patients with mild to moderate SDB who cannot tolerate CPAP. Therapy with CPAP works by splinting the upper airway to alleviate obstructive respiratory events. Mandibular repositioning devices work by repositioning the jaw or tongue to maintain upper airway patency, but patients with stroke may have difficulty manipulating these devices due to motor and coordination challenges.

Post-stroke, a high prevalence of patients (up to 75%) suffer from SDB, warranting treatment.^14,15,16,17 SDB should be suspected, even in the absence of obesity or sleepiness.¹⁸ Neurologic outcomes of post-stroke patients can be improved through early recognition and treatment of SDB.⁵ Treating SDB post-stroke may improve a patient's functional outcome, cognitive, mental, and behavioral abilities, and overall quality of life.^19,20

Regarding prevention of stroke, hypertension and diabetes are the two most common co-morbid conditions in OSA, and should be a cause for screening and treatment of SDB.⁵ Several questionnaires are available to aid in identifying patients with potential sleep issues, such as the Pittsburgh Sleep Quality Index (http://www.sleep.pitt.edu/content.asp?id=1484&subid=2316) and the STOP-BANG Questionnaire (http://www.ncbi.nlm.nih.gov/pubmed/23771818).

In conclusion, SDB is prevalent in the general population and particularly in patients with or at risk for cardiovascular disease. Evidence has identified SDB is an independent risk factor for stroke. The risk of stroke or death increases for patients even with mildly elevated AHI's.^21,12 For this reason, effective screening, diagnosis, and treatment of SDB are needed to decrease risk of cardiovascular disease, as well as improve outcomes post-stroke.

References

1. Cheyne J. A case of apoplexy in which the fleshy part of the heart was converted into fat. (1939) Dublin Hop Rep 1818; 2: 216-218. Williams & Wilkins
2. Broadbent WH: On Cheyne-Stokes respiration in cerebral hemorrhage. Lancet 1877; 1:307-309
3. Bassetti, C., Sleep and Stroke. Chapter 88, 993-1015 chapter in Kryger, M., Roth, R., Dement, W. (2011) Principles and practice of sleep medicine. 5th edition. Saunders/Elsevier.
4. Johnson KG, and Johnson DC: Frequency of sleep apnea in stroke and TIA patients: a metaanalysis. J Clin Sleep Med 2010;15:131-137
5. Mohsenin, V. Obstructive Sleep Apnea: A New Preventative and Therapeutic Target for Stroke A new kid on the block. Am J Med 2015; S0002-9343:00169-2.
6. Diaz J, and Sempere AP: Cerebral ischemia: new risk factors. Cerebrovasc Dis 2004; 17:43-50
7. Martínez-García MA, Campos-Rodríguez F, Soler-Cataluña JJ, et al. Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment Eur Respir J 2012;39:906-12
8. Portaluppi F, Cortelli P, Calandra Buonaura G, Smolensky MH, Fabbian F. Do Restless Legs Syndrome (RLS) and periodic limb movements of sleep (PLMS) play a role in nocturnal hypertension and increased cardiovascular risk of renally impaired patients? Chronobiology International 2009;26:1206–21.
9. Lindner A, Fornadi K, Lazar AS, et al. Periodic limb movements in sleep are associated with stroke and cardiovascular risk factors in patients with renal failure. J Sleep Res 2012; 21:297-307.
10. La Manna G, Pizza F, Persici E, et al. Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment. Nephrol Dial Transplant 2010; 26:1976-83.
11. B. Jafari, J.A. Elias, V. Mohsenin. Increased plasma YKL-40/chitinase-3-like-protein-1 is associated with endothelial dysfunction in obstructive sleep apnea. PLoS One 2014; 9:e98629
12. Somers VK, White DP, Amin R, et al. Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. J Am Coll Cardiol 2008; 52:686–717
13. C.L. Bassetti, M. Milanova, M. Gugger. Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke 2006; 37: 967–972
14. Dyken ME, Im KB. Obstructive sleep apnea and stroke. Chest 2009;136:1668-77.
15. Yaggi H, Mohsenin V. Obstructive sleep apnoea and stroke. Lancet Neurol 2004; 3:333-42.
16. Hudgel DW, Devadatta P, Quadri M, Sioson ER, Hamilton H. Mechanism of sleep-induced periodic breathing in convalescing stroke patients and healthy elderly subjects. Chest 1993;104:1503-10.
17. Mohsenin V, Valor R. Sleep apnea in patients with hemispheric stroke. Arch Phys Med Rehabil 1995; 76:71-6.
18. D. Brooks, L. Davis, N. Vujovic-Zotovic, et al. Sleep-disordered breathing in patients enrolled in an inpatient stroke rehabilitation program. Arch Phys Med Rehabil 2010; 91:659–662
19. Good DC, Henkle JQ, Gelber D, Welsh J, Verhulst S. Sleep-disordered breathing and poor functional outcome after stroke. Stroke 1996;27:252-9;
20. Sandberg O, Franklin KA, Bucht G, Gustafson Y. Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke. J Am Geriatr Soc 2001;49:391-7.
21. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, and Mohsenin, V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005; 353:2034-2041.

Keywords: Airway Obstruction, Apnea, Arousal, Atrial Fibrillation, Blood Pressure, Brain, Cognition, Continuous Positive Airway Pressure, Depression, Diabetes Mellitus, Diet, Dyslipidemias, Dyspnea, Headache, Homocysteine, Hypertension, Hypoventilation, Motor Activity, Oxygen, Panic Disorder, Polysomnography, Prevalence, Quality of Life, Respiratory Sounds, Restless Legs Syndrome, Risk Factors, Sensation, Sleep, Sleep Apnea, Central, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Sleep Wake Disorders, Sleep Initiation and Maintenance Disorders, Smoking, Snoring, Stroke, Sweating, Vascular Diseases

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