Obstructive Sleep Apnea and Heart Disease

1. Obstructive Sleep Apnea and Heart Disease Cardiology Cath Conference 3/31/11 Andrew Binder

2. Overview • Prevalence and Definition • General hemodynamic effects • OSA and specific cardiovascular effects • HTN • Heart Failure • Atherosclerosis and Inflammation • Arrhythmias • Pulmonary Hypertension • Treatment of OSA

3. Obstructive Sleep Apnea • Affects 15 million adult Americans • Repetitive collapse of the pharynx that triggers apneas during sleep • Intermittent hypoxia • Exaggerated negative intrathoracic pressures • Surges in sympathetic nervous system activity • Increased blood pressure • Frequent awakenings Kasai et al. JACC 2011

4. Pathogenesis of OSA • OSA patients usually have a narrow pharynx • At sleep onset there is loss of pharyngeal dilator muscle tone which causes complete or partial pharyngeal collapse causing obstructive apneas and hypopneas. Kasai et al. JACC 2011

5. Screening for OSA • Epworth Sleepiness Scale • Berlin questionnaire • Overnight oximetry – most often used in clinical practice Spaak J et al. Hypertension 2005

6. Definition • Apnea - > 90% reduction in tidal volume lasted > 10 seconds • Hypopnea – reduction in tidal volume of 50 – 90%, lasted > 10 seconds accompanied by > 3% decrease in oxygen saturation or terminated by arousal from sleep • AHI – apnea-hypopnea index > 5 = OSA disorder Kasai et al. JACC 2011

7. Diagnosis of OSA • OSA syndrome • > 5 episodes of apnea or hypopnea per hour of sleep • Hypersomnolence • Episodes of choking or gasping during sleep • Recurrent awakenings • Unrefreshing sleep • Daytime fatigue • Impaired concentration or memory Kasai et al. JACC 2011

8. OSA

9. Sleep Disordered Breathing- “The basic definition” Obstructive Sleep Apnea Central Sleep Apnea Cheyne-Stokes Respiration Idiopathic Central Sleep Apnea Syndrome

10. Mechanisms of Disease Spaak J et al. Hypertension 2005

11. Prevalence of OSA in Stable Outpatients with Heart Failure Prevalence

12. Prevalence of OSA in HF Kasai et al. JACC 2011

13. Risk Factors for OSA • Age: females after menopause • Obesity: particularly males and middle aged women • Neck circumference • Craniofacial predisposition and family history • Certain racial groups • Cardiovascular disease and heart failure

14. Symptoms of OSA • Snoring • Excessive daytime sleepiness • Witnessed apneas • Poor memory and concentration, irritability or personality changes • Other: Dry throat, morning headache, and nocturia

15. Physical Examination in OSA • Malampati Class • Obesity and thick neck • > 17 inch males • > 16 inch females • Craniofacial anatomy • Inferiorly positioned hyoid bone • Mandibular insufficiency • Increased mid-facial height • Nasal obstruction

16. Upper Airway in OSA Normal Patient

17. Normal Individual Obese Patient

18. Sleep – Cardiovascular Quiescence • Normally, during non-REM sleep: • Decrease in metabolic rate, sympathetic nervous system activity (SNA), blood pressure (BP), and heart rate (HR) • Increase in cardiac vagal activity • Disrupted by OSA • HF patients sleep approximately 1.3 hours less than subjects without HF

19. C Kasai et al. JACC 2011

20. Effects of OSA Spaak J et al. Hypertension 2005

21. OSA • OSA has been independently linked to multiple cardiovascular outcomes • HTN • CVA • Myocardial Ischemia • Arrhythmias • Fatal and nonfatal cardiovascular events • All cause mortality • Treatment of OSA may represent a novel target to reduce cardiovascular health outcomes. Selim et al. Clim Chest Med 2010

22. Hypertension • 50% of OSA patients are hypertensive • 30% of hypertensive patients also have OSA, often undiagnosed • Non-dippers • Logan et al found the prevalence of OSA in resistant hypertension to be 83% Logan et al. J Hypertension 2001

23. Hypertension Peppard PE et al. NEJM 2000

24. Hypertension • Multiple studies with conflicting results of effect of treatment of OSA on hypertension • 3 recent meta-analyses shown significant but modest reduction in BP (~ 2 mm Hg). • Patient with more severe OSA, difficult to control hypertension, and better CPAP compliance had more substantial BP reduction with CPAP. Haentjens P et al. Arch Intern Med 2007 Bazzano et al Hypertension 2007 Alajmi et al Lung 2007

25. Heart Failure • 11% - 37% of patients with systolic dysfunction had OSA detected on polysomnography • Very few complained of excessive daytime sleepiness • Men > Women (38% vs. 31%) • Major risk factor in men: obesity • Major risk factor in women: older age • Prospective study where polysomnography was performed on all consenting patients newly referred to a tertiary hospital heart failure clinic • 26% had OSA with an AHI > 15 • OSA noted in > 50% of HFPEF Spaak J et al. Hypertension 2005

26. OSA and Heart Failure • Most direct mechanism in which OSA can induced LV dysfunction is by raising BP. • Also: • Increased sympathetic outflow • Increased LV afterload acutely and chronically • Hypoxia induced increase of RV afterload • Increased risk of myocardial infarction Spaak J et al. Hypertension 2005

27. OSA and Heart Failure • OSA Heart Failure Yumino et al. Circulation 2010

28. Heart Failure Spaak J et al. Hypertension 2005, Usui K et al. JACC 2005

29. Kaplan–Meier survival curves of death from any cause in patients with (A) ischemic heart failure (HF) and (B) non-ischemic HF. Yumino D et al. Heart 2009;95:819-824 ©2009 by BMJ Publishing Group Ltd and British Cardiovascular Society

30. ICD therapy and SDB Serizawa N et al. Am J Cardiol 2008

31. Day-Night pattern of ICD therapy Serizawa N et al. Am J Cardiol 2008

32. Effect of OSA treatment on HF Spaak J et al. Hypertension 2005

33. Atherosclerosis Savransky et al. Am J Respir Crit Care Med 2007

34. Endothelial Effects • Oxidative stress  reactive oxygen species  inflammation Minoguchi et al. Am J Respir Crit Care Med 2005

35. CIMT and OSA Drager et al. Am J Respir Crit Care Med 2005

36. Treatment of OSA and CIMT Drager et al. Am J Respir Crit Care Med 2007

37. CPAP and inflammation Yokoe et al. Circulation 2003

38. Myocardial Ischemia • Prevalence of SDB in CAD patients is up to 2-fold greater than in non-CAD subjects. Spaak J et al. Hypertension 2005

39. Myocardial Ischemia and Infarction • Ischemia • Severe intermittent hypoxemia • Acidosis • Increased BP • Sympathetic vasoconstriction • Changes in intra thoracic and cardiac trans mural pressures • CAD • Endothelial dysfunction • Systemic inflammation Spaak J et al. Hypertension 2005

40. Multivariate analysis for the association between OSA severity measured by AHI quartile and CAC. Sorajja D et al. Chest 2008;133:927-933 ©2008 by American College of Chest Physicians

41. Sudden Cardiac Death in OSA N Engl J Med 2005;352:1206-14.

42. Arrhythmias • Nocturnal arrhythmias have been shown to occur in up to 50% of OSA patients. • Nonsustainted ventricular tachycardia • Sinus arrest • Second degree AV block • Frequent PVC’s Franz et al. Circulation 1992 Aviles et al. Circulation 2003

43. Arrhythmias and OSA Mehra R et al. Am J Respir Crit Care Med 2006

44. Brady arrhythmias • Apnea and hypoxemia in OSA can elicit the diving reflex resulting in cardiac vagal activation • AV blocks or asystole may develop, even in the absence of cardiac conduction disease. • 59% of patients with pacemakers have sleep apnea Garrigue et al. Circulation 2007

45. Pulmonary Hypertension • 16% - 42% of patients with OSA have PH • PH in OSA patients is associated with: • Obesity • Poor lung function • Degree and duration of hypoxemia • Hypercapnea • Not associated with age, gender or OSA severity • Typically mean PAP is only mildly elevated unless there is underlying lung or heart disease. Chaouat A et al. Chest 1996 Selim et al. Clin Chest Med 2010

46. Pulmonary Hypertension • Hypoxemia-induced pulmonary vasoconstriction leads to vascular remodeling • Large negative intrathoracic pressures generated during obstructive apneas • increase LV transmural pressure causing greater myocardial oxygen demand, reduced CO, and increased wedge pressure. • Increase wall stiffness of large vessels and increase impedance Spaak J et al. Hypertension 2005

47. Pulmonary Hypertension • Randomized, cross-over trial • 23 middle-aged OSA and otherwise healthy patients • 10 control subjects • Measured PA pressure by TTE Arias et al. Eur Heart Journal 2006

48. Individual values for the PASP in OSA patients and control subjects. Arias M A et al. Eur Heart J 2006;27:1106-1113 © The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

49. Individual values for the PASP after both sham and effective CPAP treatment in OSA patients. Arias M A et al. Eur Heart J 2006;27:1106-1113 © The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

50. Treatment of OSA • Obesity is single most important cause of OSA • Weight loss leads to • Decrease in AHI • Improved sleep efficiency • Decreased snoring • Improved oxygenation • Positional apnea