Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 147 No. 2122 (2017)

Sleep-disordered breathing: clinical features, pathophysiology and diagnosis

Cite this as:
Swiss Med Wkly. 2017;147:w14436


In recent decades, the association between sleep-disordered breathing (SDB) and cardio- and cerebrovascular diseases (including hypertension, coronary heart disease and stroke) has been the focus of interest of both clinicians and researchers. A growing concern is the increasing prevalence of SDB in the general population, which can be partly explained by the rise in obesity prevalence and population aging, as well as by the development of enhanced diagnostic tools and approaches. Because of evidence of adverse long-term effects of SDB on cardiovascular morbidity and overall mortality, systematic screening for SDB should be considered for populations at risk. The evidence of a long-term benefit of treatment for SDB, however, is still controversial and the best management approaches are still unclear.

This article summarises available epidemiological data and focuses on the main pathophysiological mechanisms linking SDB to cardio- and cerebrovascular disorders. We will also give a critical overview of the current diagnostic procedures. The available treatment approaches and their prognostic effects on cardio- and cerebrovascular health will be discussed in a second paper.


  1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328(17):1230–5.
  2. Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Respir Med. 2015;3(4):310–8.
  3. Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177(9):1006–14.
  4. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al.; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–236.. Correction in: Stroke. 2015;46(2):e54. doi: 10.1161/STR.0000000000000059
  5. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr, Drazner MH, et al.; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American college of cardiology foundation/american heart association task force on practice guidelines. J Am Coll Cardiol. 2013;62(16):e147–239.
  6. Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS, et al.; American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Circulation. 2015;131(19):e435–70.
  7. Hermann DM, Bassetti CL. Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery. Neurology. 2016;87(13):1407–16.
  8. American Academy of Sleep Medicine. International Classification of Sleep Disorders. Vol 3d ed. Darien, IL: American Academy of Sleep Medicine; 2014.
  9. Douglas NJ. Control of ventilation during sleep. Clin Chest Med. 1985;6(4):563–75.
  10. Malik V, Smith D, Lee-Chiong T, Jr. Respiratory Physiology During Sleep. Sleep Med Clin. 2012;7(3):497–505.
  11. Parati G, Lombardi C, Hedner J, Bonsignore MR, Grote L, Tkacova R, et al.; EU COST Action B26 members. Recommendations for the management of patients with obstructive sleep apnoea and hypertension. Eur Respir J. 2013;41(3):523–38.
  12. Aurora RN, Chowdhuri S, Ramar K, Bista SR, Casey KR, Lamm CI, et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses. Sleep. 2012;35(1):17–40.
  13. Greenberg H, Lakticova V, Scharf SM. Sleep Breathing Disorders. In: Principles and Practice of Sleep Medicine. 6th Ed. Ed. by M. Kryger et Al. Ch. 114. Vol; 2016:1110-1124.
  14. Eckert D, Butler J. Respiratory physiology: understanding the control of ventilation. In: Principles and Practice of Sleep Medicine. 6th Ed. Ed. by M. Kryger et Al. Ch. 16-17. Vol; 2016:167-173.
  15. Shahar E, Whitney CW, Redline S, Lee ET, Newman AB, Nieto FJ, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med. 2001;163(1):19–25.
  16. Gottlieb DJ, Yenokyan G, Newman AB, O’Connor GT, Punjabi NM, Quan SF, et al. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation. 2010;122(4):352–60.
  17. Gilat H, Vinker S, Buda I, Soudry E, Shani M, Bachar G. Obstructive sleep apnea and cardiovascular comorbidities: a large epidemiologic study. Medicine (Baltimore). 2014;93(9):e45.
  18. Bassetti C, Aldrich MS, Chervin RD, Quint D. Sleep apnea in patients with transient ischemic attack and stroke: a prospective study of 59 patients. Neurology. 1996;47(5):1167–73.
  19. Hermann DM, Bassetti CL. Sleep-related breathing and sleep-wake disturbances in ischemic stroke. Neurology. 2009;73(16):1313–22.
  20. Johnson KG, Johnson DC. Frequency of sleep apnea in stroke and TIA patients: a meta-analysis. JCSM. 2010;6(2):131-137.
  21. Gami AS, Pressman G, Caples SM, Kanagala R, Gard JJ, Davison DE, et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation. 2004;110(4):364–7.
  22. Reichmuth KJ, Austin D, Skatrud JB, Young T. Association of sleep apnea and type II diabetes: a population-based study. Am J Respir Crit Care Med. 2005;172(12):1590–5.
  23. Tasali E, Mokhlesi B, Van Cauter E. Obstructive sleep apnea and type 2 diabetes: interacting epidemics. Chest. 2008;133(2):496–506.
  24. Lam JCM, Mak JCW, Ip MSM. Obesity, obstructive sleep apnoea and metabolic syndrome. Respirology. 2012;17(2):223–36.
  25. Xu H, Guan J, Yi H, Zou J, Meng L, Tang X, et al.; Shanghai Sleep Health Study Research Group. Elevated low-density lipoprotein cholesterol is independently associated with obstructive sleep apnea: evidence from a large-scale cross-sectional study. Sleep Breath. 2016;20(2):627–34.
  26. Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012;307(20):2169–76.
  27. Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med. 1997;157(15):1746–52.
  28. Broström A, Sunnergren O, Årestedt K, Johansson P, Ulander M, Riegel B, et al. Factors associated with undiagnosed obstructive sleep apnoea in hypertensive primary care patients. Scand J Prim Health Care. 2012;30(2):107–13.
  29. Demede M, Pandey A, Zizi F, Bachmann R, Donat M, McFarlane SI, et al. Resistant hypertension and obstructive sleep apnea in the primary-care setting. Int J Hypertens. 2011;2011:340929.
  30. Di Guardo A, Profeta G, Crisafulli C, Sidoti G, Zammataro M, Paolini I, et al. Obstructive sleep apnoea in patients with obesity and hypertension. Br J Gen Pract. 2010;60(574):325–8.
  31. Börgel J, Sanner BM, Keskin F, Bittlinsky A, Bartels NK, Büchner N, et al. Obstructive sleep apnea and blood pressure. Interaction between the blood pressure-lowering effects of positive airway pressure therapy and antihypertensive drugs. Am J Hypertens. 2004;17(12 Pt 1):1081–7.
  32. Min HJ, Cho YJ, Kim CH, Kim DH, Kim HY, Choi JI, et al. Clinical Features of Obstructive Sleep Apnea That Determine Its High Prevalence in Resistant Hypertension. Yonsei Med J. 2015;56(5):1258–65.
  33. Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811–7.
  34. Mooe T, Franklin KA, Holmström K, Rabben T, Wiklund U. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1910–3.
  35. Peker Y, Kraiczi H, Hedner J, Löth S, Johansson A, Bende M. An independent association between obstructive sleep apnoea and coronary artery disease. Eur Respir J. 1999;14(1):179–84.
  36. Aronson D, Nakhleh M, Zeidan-Shwiri T, Mutlak M, Lavie P, Lavie L. Clinical implications of sleep disordered breathing in acute myocardial infarction. PLoS One. 2014;9(2):e88878.
  37. Glantz H, Thunström E, Herlitz J, Cederin B, Nasic S, Ejdebäck J, et al. Occurrence and predictors of obstructive sleep apnea in a revascularized coronary artery disease cohort. Ann Am Thorac Soc. 2013;10(4):350–6.
  38. Herrscher TE, Akre H, Øverland B, Sandvik L, Westheim AS. High prevalence of sleep apnea in heart failure outpatients: even in patients with preserved systolic function. J Card Fail. 2011;17(5):420–5.
  39. Lanfranchi PA, Somers VK, Braghiroli A, Corra U, Eleuteri E, Giannuzzi P. Central sleep apnea in left ventricular dysfunction: prevalence and implications for arrhythmic risk. Circulation. 2003;107(5):727–32.
  40. Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med. 1999;160(4):1101–6.
  41. Guilleminault C, Connolly SJ, Winkle RA. Cardiac arrhythmia and conduction disturbances during sleep in 400 patients with sleep apnea syndrome. Am J Cardiol. 1983;52(5):490–4.
  42. Grimm W, Apelt S, Timmesfeld N, Koehler U. Sleep-disordered breathing in patients with implantable cardioverter-defibrillator. Europace. 2013;15(4):515–22.
  43. Koshino Y, Satoh M, Katayose Y, Yasuda K, Tanigawa T, Takeyasu N, et al. Association of sleep-disordered breathing and ventricular arrhythmias in patients without heart failure. Am J Cardiol. 2008;101(6):882–6.
  44. Garrigue S, Pépin J-L, Defaye P, Murgatroyd F, Poezevara Y, Clémenty J, et al. High prevalence of sleep apnea syndrome in patients with long-term pacing: the European Multicenter Polysomnographic Study. Circulation. 2007;115(13):1703–9.
  45. Gami AS, Howard DE, Olson EJ, Somers VK. Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med. 2005;352(12):1206–14.
  46. Gami AS, Hodge DO, Herges RM, Olson EJ, Nykodym J, Kara T, et al. Obstructive sleep apnea, obesity, and the risk of incident atrial fibrillation. J Am Coll Cardiol. 2007;49(5):565–71.
  47. Bitter T, Langer C, Vogt J, Lange M, Horstkotte D, Oldenburg O. Sleep-disordered breathing in patients with atrial fibrillation and normal systolic left ventricular function. Dtsch Arztebl Int. 2009;106(10):164–70. doi:.
  48. Altmann DR, Ullmer E, Rickli H, Maeder MT, Sticherling C, Schaer BA, et al. Clinical impact of screening for sleep related breathing disorders in atrial fibrillation. Int J Cardiol. 2012;154(3):256–8.
  49. Stahl SM, Yaggi HK, Taylor S, Qin L, Ivan CS, Austin C, et al. Infarct location and sleep apnea: evaluating the potential association in acute ischemic stroke. Sleep Med. 2015;16(10):1198–203.
  50. Ifergane G, Ovanyan A, Toledano R, Goldbart A, Abu-Salame I, Tal A, et al. Obstructive Sleep Apnea in Acute Stroke: A Role for Systemic Inflammation. Stroke. 2016;47(5):1207–12.
  51. Sahlin C, Sandberg O, Gustafson Y, Bucht G, Carlberg B, Stenlund H, et al. Obstructive sleep apnea is a risk factor for death in patients with stroke: a 10-year follow-up. Arch Intern Med. 2008;168(3):297–301.
  52. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353(19):2034–41.
  53. Ehrhardt J, Schwab M, Finn S, Guenther A, Schultze T, Witte OW, et al. Sleep apnea and asymptomatic carotid stenosis: a complex interaction. Chest. 2015;147(4):1029–36.
  54. Laks L, Lehrhaft B, Grunstein RR, Sullivan CE. Pulmonary hypertension in obstructive sleep apnoea. Eur Respir J. 1995;8(4):537–41. doi:.
  55. Kessler R, Chaouat A, Weitzenblum E, Oswald M, Ehrhart M, Apprill M, et al. Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences. Eur Respir J. 1996;9(4):787–94.
  56. Minic M, Granton JT, Ryan CM. Sleep disordered breathing in group 1 pulmonary arterial hypertension. J Clin Sleep Med. 2014;10(3):277–83. doi:.
  57. Lopez PP, Stefan B, Schulman CI, Byers PM. Prevalence of sleep apnea in morbidly obese patients who presented for weight loss surgery evaluation: more evidence for routine screening for obstructive sleep apnea before weight loss surgery. Am Surg. 2008;74(9):834–8.
  58. Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol (1985). 2005;99(4):1592–9.
  59. Botros N, Concato J, Mohsenin V, Selim B, Doctor K, Yaggi HK. Obstructive sleep apnea as a risk factor for type 2 diabetes. Am J Med. 2009;122(12):1122–7.
  60. Schober AK, Neurath MF, Harsch IA. Prevalence of sleep apnoea in diabetic patients. Clin Respir J. 2011;5(3):165–72.
  61. Zhang P, Zhang R, Zhao F, Heeley E, Chai-Coetzer CL, Liu J, et al. The prevalence and characteristics of obstructive sleep apnea in hospitalized patients with type 2 diabetes in China. J Sleep Res. 2016;25(1):39–46.
  62. Markou N, Kanakaki M, Myrianthefs P, Hadjiyanakos D, Vlassopoulos D, Damianos A, et al. Sleep-disordered breathing in nondialyzed patients with chronic renal failure. Lung. 2006;184(1):43–9.
  63. Nicholl DDM, Ahmed SB, Loewen AHS, Hemmelgarn BR, Sola DY, Beecroft JM, et al. Clinical presentation of obstructive sleep apnea in patients with chronic kidney disease. J Clin Sleep Med. 2012;8(4):381–7. doi:.
  64. Forni Ogna V, Ogna A, Pruijm M, et al. Prevalence and Diagnostic Approach to Sleep Apnea in Hemodialysis Patients: A Population Study. BioMed Res Intern. 2015.2015:1–9. doi:.
  65. Merlino G, Piani A, Dolso P, Adorati M, Cancelli I, Valente M, et al. Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy. Nephrol Dial Transplant. 2006;21(1):184–90.
  66. Unruh ML, Sanders MH, Redline S, Piraino BM, Umans JG, Hammond TC, et al. Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. J Am Soc Nephrol. 2006;17(12):3503–9.
  67. Dharia SM, Unruh ML, Brown LK. Central Sleep Apnea in Kidney Disease. Semin Nephrol. 2015;35(4):335–46.
  68. Walia HK, Li H, Rueschman M, Bhatt DL, Patel SR, Quan SF, et al. Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use. J Clin Sleep Med. 2014;10(8):835–43. doi:.
  69. Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19(12):2271–7.
  70. Konecny T, Kuniyoshi FHS, Orban M, Pressman GS, Kara T, Gami A, et al. Under-diagnosis of sleep apnea in patients after acute myocardial infarction. J Am Coll Cardiol. 2010;56(9):742–3.
  71. Bassetti CL, Milanova M, Gugger M. Sleep-disordered breathing and acute ischemic stroke: diagnosis, risk factors, treatment, evolution, and long-term clinical outcome. Stroke. 2006;37(4):967–72.
  72. Siccoli MM, Valko PO, Hermann DM, Bassetti CL. Central periodic breathing during sleep in 74 patients with acute ischemic stroke - neurogenic and cardiogenic factors. J Neurol. 2008;255(11):1687–92.
  73. Javaheri S. Central sleep apnea in congestive heart failure: prevalence, mechanisms, impact, and therapeutic options. Semin Respir Crit Care Med. 2005;26(1):44–55.
  74. Tilkian AG, Guilleminault C, Schroeder JS, Lehrman KL, Simmons FB, Dement WC. Hemodynamics in sleep-induced apnea. Studies during wakefulness and sleep. Ann Intern Med. 1976;85(6):714–9.
  75. Lévy P, McNicholas WT. Sleep apnoea and hypertension: time for recommendations. Eur Respir J. 2013;41(3):505–6.
  76. Fava C, Dorigoni S, Dalle Vedove F, Danese E, Montagnana M, Guidi GC, et al. Effect of CPAP on blood pressure in patients with OSA/hypopnea: a systematic review and meta-analysis. Chest. 2014;145(4):762–71.
  77. Martínez-García MA, Capote F, Campos-Rodríguez F, Lloberes P, Díaz de Atauri MJ, Somoza M, et al.; Spanish Sleep Network. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013;310(22):2407–15.
  78. Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, Martínez-Alonso M, Carmona C, Barceló A, et al.; Spanish Sleep And Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;307(20):2161–8.
  79. Parra O, Arboix A, Bechich S, García-Eroles L, Montserrat JM, López JA, et al. Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack. Am J Respir Crit Care Med. 2000;161(2 Pt 1):375–80.
  80. Camilo MR, Schnitman SV, Sander HH, Eckeli AL, Fernandes RM, Leite JP, et al. Sleep-disordered breathing among acute ischemic stroke patients in Brazil. Sleep Med. 2016;19:8–12.
  81. Schipper MH, Jellema K, Rijsman RM. Occurrence of Obstructive Sleep Apnea Syndrome in Patients with Transient Ischemic Attack. J Stroke Cerebrovasc Dis. 2016;25(5):1249–53.
  82. Hsieh SW, Lai CL, Liu CK, Hsieh CF, Hsu CY. Obstructive sleep apnea linked to wake-up strokes. J Neurol. 2012;259(7):1433–9.
  83. Šiarnik P, Kollár B, Čarnická Z, Šurda P, Klobučníková K, Sýkora M, et al. Association of Sleep Disordered Breathing with Wake-Up Acute Ischemic Stroke: A Full Polysomnographic Study. J Clin Sleep Med. 2016;12(4):549–54. Available at:
  84. Koo BB, Bravata DM, Tobias LA, Mackey JS, Miech EJ, Matthias MS, et al. Observational study of obstructive sleep apnea in wake-up stroke: The SLEEP TIGHT study. Cerebrovasc Dis. 2016;41(5-6):233–41.
  85. Bassetti CL, Hermann DM. Sleep and stroke. Handb Clin Neurol. 2011;99:1051–72.
  86. Iranzo A, Santamaría J, Berenguer J, Sánchez M, Chamorro A. Prevalence and clinical importance of sleep apnea in the first night after cerebral infarction. Neurology. 2002;58(6):911–6.
  87. Harbison J, Ford GA, James OFW, Gibson GJ. Sleep-disordered breathing following acute stroke. QJM. 2002;95(11):741–7.
  88. Bonnin-Vilaplana M, Arboix A, Parra O, García-Eroles L, Montserrat JM, Massons J. Cheyne-stokes respiration in patients with first-ever lacunar stroke. Sleep Disord. 2012;2012:257890.
  89. Stone KL, Blackwell TL, Ancoli-Israel S, Barrett-Connor E, Bauer DC, Cauley JA, et al.; Osteoporotic Fractures in Men (MrOS) Study Research Group. Sleep Disordered Breathing and Risk of Stroke in Older Community-Dwelling Men. Sleep. 2016;39(3):531–40.
  90. Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O’Connor GT, Resnick HE, et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med. 2010;182(2):269–77.
  91. Loke YK, Brown JWL, Kwok CS, Niruban A, Myint PK. Association of obstructive sleep apnea with risk of serious cardiovascular events: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2012;5(5):720–8.
  92. Parra O, Arboix A, Montserrat JM, Quintó L, Bechich S, García-Eroles L. Sleep-related breathing disorders: impact on mortality of cerebrovascular disease. Eur Respir J. 2004;24(2):267–72.
  93. Birkbak J, Clark AJ, Rod NH. The effect of sleep disordered breathing on the outcome of stroke and transient ischemic attack: a systematic review. J Clin Sleep Med. 2014;10(1):103–8. doi:.
  94. Parra O, Sánchez-Armengol A, Bonnin M, Arboix A, Campos-Rodríguez F, Pérez-Ronchel J, et al. Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial. Eur Respir J. 2011;37(5):1128–36.
  95. Parra O, Sánchez-Armengol Á, Capote F, Bonnin M, Arboix A, Campos-Rodríguez F, et al. Efficacy of continuous positive airway pressure treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a randomized controlled trial. J Sleep Res. 2015;24(1):47–53.
  96. Bravata DM, Concato J, Fried T, Ranjbar N, Sadarangani T, McClain V, et al. Continuous positive airway pressure: evaluation of a novel therapy for patients with acute ischemic stroke. Sleep. 2011;34(9):1271–7. doi:.
  97. Cereda CW, Petrini L, Azzola A, Ciccone A, Fischer U, Gallino A, et al. Sleep-disordered breathing in acute ischemic stroke and transient ischemic attack: effects on short- and long-term outcome and efficacy of treatment with continuous positive airways pressure--rationale and design of the SAS CARE study. Int J Stroke. 2012;7(7):597–603.
  98. Bassetti CL, Ferini-Strambi L, Brown S, Adamantidis A, Benedetti F, Bruni O, et al. Neurology and psychiatry: waking up to opportunities of sleep.: State of the art and clinical/research priorities for the next decade. Eur J Neurol. 2015;22(10):1337–54.
  99. Rosenzweig I, Glasser M, Polsek D, Leschziner GD, Williams SCR, Morrell MJ. Sleep apnoea and the brain: a complex relationship. Lancet Respir Med. 2015;3(5):404–14.
  100. Lee C-H, Khoo S-M, Chan MY, Wong HB, Low AF, Phua QH, et al. Severe obstructive sleep apnea and outcomes following myocardial infarction. J Clin Sleep Med. 2011;7(6):616–21. doi:.
  101. Gami AS, Olson EJ, Shen WK, Wright RS, Ballman KV, Hodge DO, et al. Obstructive sleep apnea and the risk of sudden cardiac death: a longitudinal study of 10,701 adults. J Am Coll Cardiol. 2013;62(7):610–6.
  102. Kuniyoshi FHS, Garcia-Touchard A, Gami AS, Romero-Corral A, van der Walt C, Pusalavidyasagar S, et al. Day-night variation of acute myocardial infarction in obstructive sleep apnea. J Am Coll Cardiol. 2008;52(5):343–6.
  103. Marshall NS, Wong KKH, Cullen SRJ, Knuiman MW, Grunstein RR. Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort. J Clin Sleep Med. 2014;10(4):355–62. doi:.
  104. Marin JM, Carrizo SJ, Vicente E, Agusti AGN. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365(9464):1046–53.
  105. Marshall NS, Wong KKH, Liu PY, Cullen SRJ, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep. 2008;31(8):1079–85.
  106. Monahan K, Redline S. Role of obstructive sleep apnea in cardiovascular disease. Curr Opin Cardiol. 2011;26(6):541–7.
  107. Sorajja D, Gami AS, Somers VK, Behrenbeck TR, Garcia-Touchard A, Lopez-Jimenez F. Independent association between obstructive sleep apnea and subclinical coronary artery disease. Chest. 2008;133(4):927–33.
  108. Milleron O, Pillière R, Foucher A, de Roquefeuil F, Aegerter P, Jondeau G, et al. Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study. Eur Heart J. 2004;25(9):728–34.
  109. Garcia-Rio F, Alonso-Fernández A, Armada E, Mediano O, Lores V, Rojo B, et al. CPAP effect on recurrent episodes in patients with sleep apnea and myocardial infarction. Int J Cardiol. 2013;168(2):1328–35.
  110. Simantirakis EN, Schiza SI, Marketou ME, Chrysostomakis SI, Chlouverakis GI, Klapsinos NC, et al. Severe bradyarrhythmias in patients with sleep apnoea: the effect of continuous positive airway pressure treatment: a long-term evaluation using an insertable loop recorder. Eur Heart J. 2004;25(12):1070–6.
  111. Fietze I, Röttig J, Quispe-Bravo S, Riedel F, Witte J, Baumann G, et al. Sleep apnea syndrome in patients with cardiac pacemaker. Respiration. 2000;67(3):268–71.
  112. Becker HF, Koehler U, Stammnitz A, Peter JH. Heart block in patients with sleep apnoea. Thorax. 1998;53(Suppl 3):S29–32.
  113. Koehler U, Fus E, Grimm W, Pankow W, Schäfer H, Stammnitz A, et al. Heart block in patients with obstructive sleep apnoea: pathogenetic factors and effects of treatment. Eur Respir J. 1998;11(2):434–9.
  114. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, et al., Document Reviewers. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013;34(29):2281–329.
  115. Epstein AE, Dimarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation. 2008;117:350–408.
  116. Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107(20):2589–94. doi:.
  117. Qaddoura A, Kabali C, Drew D, van Oosten EM, Michael KA, Redfearn DP, et al. Obstructive sleep apnea as a predictor of atrial fibrillation after coronary artery bypass grafting: a systematic review and meta-analysis. Can J Cardiol. 2014;30(12):1516–22.
  118. Netzer N, Werner P, Jochums I, Lehmann M, Strohl KP. Blood flow of the middle cerebral artery with sleep-disordered breathing: correlation with obstructive hypopneas. Stroke. 1998;29(1):87–93.
  119. Pizza F, Biallas M, Kallweit U, Wolf M, Bassetti CL. Cerebral hemodynamic changes in stroke during sleep-disordered breathing. Stroke. 2012;43(7):1951–3.
  120. Coloma Navarro R, Jiménez Caballero PE, Vega G, Ayo-Martín O, Segura Martín T. Cerebral hemodynamics is altered in patients with sleep apnea/hypopnea syndrome. Springerplus. 2016;5(1):51.
  121. Narkiewicz K, van de Borne PJH, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without obstructive sleep apnea. Circulation. 1998;98(8):772–6.
  122. Narkiewicz K, Kato M, Phillips BG, Pesek CA, Davison DE, Somers VK. Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea. Circulation. 1999;100(23):2332–5.
  123. Seif F, Patel SR, Walia H, Rueschman M, Bhatt DL, Gottlieb DJ, et al. Association between obstructive sleep apnea severity and endothelial dysfunction in an increased background of cardiovascular burden. J Sleep Res. 2013;22(4):443–51.
  124. Cereda CW, Tamisier R, Manconi M, Andreotti J, Frangi J, Pifferini V, et al. Endothelial dysfunction and arterial stiffness in ischemic stroke: the role of sleep-disordered breathing. Stroke. 2013;44(4):1175–8.
  125. von Känel R, Natarajan L, Ancoli-Israel S, Mills PJ, Loredo JS, Dimsdale JE. Day/Night rhythm of hemostatic factors in obstructive sleep apnea. Sleep. 2010;33(3):371–7. Available at:
  126. Steiner S, Jax T, Evers S, Hennersdorf M, Schwalen A, Strauer BE. Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk. Cardiology. 2005;104(2):92–6.
  127. Shamsuzzaman A, Amin RS, Calvin AD, Davison D, Somers VK. Severity of obstructive sleep apnea is associated with elevated plasma fibrinogen in otherwise healthy patients. Sleep Breath. 2014;18(4):761–6.
  128. D’Silva L, Wilczynska M, Lewis K, Lawrence M, Hawkins K, Williams R, et al. Altered clot microstructure detected in obstructive sleep apnoea hypopnoea syndrome. Sleep Sci. 2016;9(1):14–9.
  129. Steffanina A, Proietti L, Antonaglia C, Palange P, Angelici E, Canipari R. The Plasminogen System and Transforming Growth Factor-β in Subjects With Obstructive Sleep Apnea Syndrome: Effects of CPAP Treatment. Respir Care. 2015;60(11):1643–51.
  130. White LH, Bradley TD. Logan a G. Pathogenesis of obstructive sleep apnoea in hypertensive patients: role of fluid retention and nocturnal rostral fluid shift. J Hum Hypertens. 2015;29(6):342–50. doi:.
  131. Kasai T, Motwani SS, Elias RM, Gabriel JM, Taranto Montemurro L, Yanagisawa N, et al. Influence of rostral fluid shift on upper airway size and mucosal water content. J Clin Sleep Med. 2014;10(10):1069–74. doi:.
  132. Lüthje L, Renner B, Kessels R, Vollmann D, Raupach T, Gerritse B, et al. Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea. Eur J Heart Fail. 2009;11(3):273–80.
  133. Sinha AM, Skobel EC, Breithardt OA, Norra C, Markus KU, Breuer C, et al. Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure. J Am Coll Cardiol. 2004;44(1):68–71.
  134. Lamba J, Simpson CS, Redfearn DP, Michael KA, Fitzpatrick M, Baranchuk A. Cardiac resynchronization therapy for the treatment of sleep apnoea: a meta-analysis. Europace. 2011;13(8):1174–9.
  135. Mihaicuta S, Grote L. Sleep-related breathing disorders. In: Sleep Medicine Textbook. Ed. by C. Bassetti, Z. Dogas, P. Peigneux. 2014:233-250.
  136. Marti-Soler H, Hirotsu C, Marques-Vidal P, Vollenweider P, Waeber G, Preisig M, et al. The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study. Lancet Respir Med. 2016;4(9):742–8.
  137. Boulos MI, Wan A, Im J, Elias S, Frankul F, Atalla M, et al. Identifying obstructive sleep apnea after stroke/TIA: evaluating four simple screening tools. Sleep Med. 2016;21(21):133–9.
  138. Brill AK, Rösti R, Hefti JP, Bassetti C, Gugger M, Ott SR. Adaptive servo-ventilation as treatment of persistent central sleep apnea in post-acute ischemic stroke patients. Sleep Med. 2014;15(11):1309–13.
  139. Albuquerque FN, Calvin AD, Sert Kuniyoshi FH, Konecny T, Lopez-Jimenez F, Pressman GS, et al. Sleep-disordered breathing and excessive daytime sleepiness in patients with atrial fibrillation. Chest. 2012;141(4):967–73.
  140. Redeker NS, Muench U, Zucker MJ, Walsleben J, Gilbert M, Freudenberger R, et al. Sleep disordered breathing, daytime symptoms, and functional performance in stable heart failure. Sleep. 2010;33(4):551–60. Available at:
  141. Katzan IL, Thompson NR, Uchino K, Foldvary-Schaefer N. A screening tool for obstructive sleep apnea in cerebrovascular patients. Sleep Med. 2016;21:70–6.
  142. Ye L, Pien GW, Ratcliffe SJ, Björnsdottir E, Arnardottir ES, Pack AI, et al. The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J. 2014;44(6):1600–7.
  143. Taranto Montemurro L, Floras JS, Millar PJ, Kasai T, Gabriel JM, Spaak J, et al. Inverse relationship of subjective daytime sleepiness to sympathetic activity in patients with heart failure and obstructive sleep apnea. Chest. 2012;142(5):1222–8.
  144. Boulos MI, Elias S, Wan A, Im J, Frankul F, Atalla M, et al. Unattended Hospital and Home Sleep Apnea Testing Following Cerebrovascular Events. J Stroke Cerebrovasc Dis. 2017;26(1):143–9.
  145. Ward NR, Roldao V, Cowie MR, Rosen SD, McDonagh TA, Simonds AK, et al. The effect of respiratory scoring on the diagnosis and classification of sleep disordered breathing in chronic heart failure. Sleep. 2013;36(9):1341–8. doi:.
  146. Alekhin M, Anishchenko L, Zhuravlev A, Ivashov SI, Korostovtseva LS, Sviryaev YV, et al. Estimation of Information Value of Diagnostic Data Obtained by Bioradiolocation Pneumography in Non-contact Screening of Sleep Apnea Syndrome. Biomed Eng (NY). 2013;47(2):96–9.
  147. Ryan CM, Wilton K, Bradley TD, Alshaer H. In-hospital diagnosis of sleep apnea in stroke patients using a portable acoustic device. Sleep Breath. 2016 Dec 2 [Epub ahead of print]
  148. Gottlieb DJ, Craig SE, Lorenzi-Filho G, Heeley E, Redline S, McEvoy RD, et al. Sleep Apnea Cardiovascular Clinical Trials-Current Status and Steps Forward: The International Collaboration of Sleep Apnea Cardiovascular Trialists. Sleep. 2013;36(7):975–80.