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Obstructive Sleep Apnea and Cardiovascular Disease Chitra Lal, MD, D-ABSM, FCCP Assistant Professor of Medicine Medical University of South Carolina, Charleston, SC Faculty Disclosures 25th Annual Update in Psychiatry/MUSC, Charleston, SC <Chitra Lal, MD, D-ABSM,FCCP> • Personal financial interests in commercial entities that are relevant to my presentation(s) or other faculty roles: • No relevant commercial interests • Non-commercial, non-governmental interests relevant to my presentation(s) or other faculty roles: • None • Tobacco industry interests: • None Specific Questions • Does OSAS play a role in the initiation of cardiac and vascular disease? • Does OSAS accelerate disease progression in patients with established cardiovascular disease? • Does OSAS treatment result in clinical improvement and reduced mortality from cardiovascular disease? Epidemiology • Obstructive sleep apnea syndrome (OSAS) affects approximately 15 million adult Americans (1) • OSAS is seen in a large proportion of patients who have hypertension, coronary artery disease, stroke and atrial fibrillation (2) • Prevalence of OSAS is 2% in women and 4% in men in the 30-60 year age group (3) (1) Caples SM et al, Obstructive sleep apnea Ann Intern Med 2005;142:187-197. (2) Lattimore JD et al, Obstructive sleep apnea and cardiovascular disease J Am Coll Cardiol 2003;41:14291437. (3) Young T et al, The occurrence of sleep-disordered breathing among middle-aged adults, NEJM1993 Apr 29;328(17):1230-5 Definitions • OSAS is characterized by repetitive interruption of ventilation during sleep caused by collapse of the pharyngeal airway • Apnea is ≥ 90% decrease in airflow for > 10 seconds • Hypopnea (recommended AASM definition) : decrease in airflow to ≥ 30% for 10 seconds with ≥ 4% desaturation • Ongoing respiratory effort characterizes obstructive events Partial and complete airway obstruction resulting in hypopnea and apnea, respectively Somers, V. K. et al. J Am Coll Cardiol 2008;52:686-717 Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply. OSAS in Adults • Mild OSAS : AHI ≥ 5/hour • Moderate OSAS : AHI ≥ 15/hour • Severe OSAS : AHI ≥ 30/hour Clinical Features of OSAS • • • • • • • • • • Daytime Sleepiness Nonrestorative sleep Witnessed apneas Insomnia Narrow upper airway Memory loss Lack of concentration Mood changes Morning headaches Polycythemia • • • • • • • • • • GERD Vivid, strange dreams Obesity ↑ neck circumference Systemic hypertension Hypercapnia Cardiovascular disease Stroke Cardiac dysrhythmias Pulmonary hypertension STOP-BANG Questionnaire • Snoring • Tiredness • Observed you stop breathing • Blood Pressure • BMI > 35 • Age > 50 • Neck Circumference > 40 cm • Gender Male High Risk : Yes to ≥ 3 items → Refer for sleep testing Cardiovascular effects of OSAS Systemic hypertension Pulmonary hypertension Arrhythmias Coronary artery disease Heart Failure Stroke OSAS and Systemic Hypertension ↑ Prevalence & incidence Doseresponse effect Treatment effect Epidemiological Data • Cross-sectional analysis of 6132 participants of Sleep Heart Health Study (4) • Age ≥ 40 years, 52.8% females (4) Nieto FJ et al, JAMA, 2000 Apr 12;283(14):1829-36 Adjusted Odds Ratio (OR) and 95% Confidence Intervals (CIs) of Hypertension by SleepDisordered Breathing Measures, Sleep Heart Health Study, 1995-1998*. Nieto, F. J. et al. JAMA 2000;283:1829-1836 Copyright restrictions may apply. Prevalence of Snoring, Mean Levels of Sleep-Disordered Breathing Indicators, and Mean Blood Pressures, by Apnea-Hypopnea Index (AHI) Category, Sleep Heart Health Study, 19951998*. Copyright restrictions may apply. Nieto, F. J. et al. JAMA 2000;283:1829-1836 OSAS and Systemic Hypertension • Prospective study of 709 participants in the Wisconsin Sleep Cohort (5) • Data analysed at baseline, after 4 years and 8 years of follow-up (5) Peppard PE et al, NEJM, 2000 May 11;342(19):1378-84 Peppard PE et al, NEJM, 2000 May 11;342(19):1378-84 OSAS and Systemic Hypertension • Double-blind, placebo-controlled trial of 86 OSAS patients randomized to receive therapeutic cpap for 3 months followed by sham-cpap for 3 months or vice-versa (6) (6) Sharma SK et al, NEJM, 2011 Dec 15;365(24):2277-86 OSAS and Resistant Hypertension • Blood pressure ≥ 140/90 mm Hg using at least 3 anti-hypertensive drugs (at least 1 diuretic) • Case-control study of 63 case patients with resistant hypertension and 63 control patients with controlled hypertension on medications (7) (7) Goncalves SC et al, Chest, 2007 Dec;132(6):1858-62 Goncalves SC et al, Chest, 2007 Dec;132(6):1858-62 Goncalves SC et al, Chest, 2007 Dec;132(6):1858-62 Comparison of CPAP and valsartan in hypertensive patients with sleep apnea Pepin JL et al, AJRCCM, 2010 Oct 1;182(7):954-60 Key Points • Systemic hypertension is more common in patients with OSAS than in those without OSAS • Severity of OSAS corresponds to likelihood of systemic hypertension • Decrease in blood pressure with cpap is small and less then with medications but significant • Consider OSAS in patients with resistant hypertension OSAS and Pulmonary Hypertension • Pulmonary hypertension (PH) in OSAS is typically mild (mean PAP ≤ 26 mm Hg) (8) • Cor pulmonale is more likely to occur in patients with diurnal hypoxemia then in those with just nocturnal hypoxemia (9) • PH can occur in OSAS in the absence of lung disease (8) • Presence of PH decreases overall survival (10) (8) Sajkov D et al, AJRCCM, 1994 Feb;149(2 Pt 1):416-22 (9) Bradley TD et al, Am Rev Repir Dis, 1985 Jun;131(6):835-9 (10) Minai OA et al, Am J Cardiol, 2009 Nov 1;104(9):1300-6 Kaplan-Meier survival curves in 83 OSAS patients, Minai OA et al, Am J Cardiol, 2009 Nov 1;104(9):1300-6 Arias MA et al, Eur Heart J, 2006 May;27(9):1106-13. Epub 2006 Feb 23 Key Points • OSAS causes mild PH • Presence of PH should prompt the clinician to screen for evidence of OSAS OSAS and Coronary Artery Disease • Severe OSAS is associated with increased morbidity and mortality due to coronary artery disease (CAD) • Prospective cohort study of 1651 men who were followed for a mean of 10 years (11) (11) Marin JM et al, Lancet, 2005 Mar 19-25;365(9464):1046-53 Marin JM et al, Lancet, 2005 Mar 19-25;365(9464):1046-53 Marin JM et al, Lancet, 2005 Mar 19-25;365(9464):1046-53 OSAS and Coronary Artery Disease • OSAS can exacerbate pre-existing CAD • Prospective cohort study of 89 consecutive patients who underwent percutaneous coronary intervention for acute CAD (12) • Incidence of major cardiac adverse events (MACE) was higher in patients with OSAS than those without OSAS (adjusted HR 11.6, 95% CI 2.2-62.2) (12) Tsurumi Y et al, Am J. Cardiol., 2007 Jan 1;99(1):26-30. Epub 2006 Nov 2 Tsurumi Y et al, Am J. Cardiol., 2007 Jan 1;99(1):26-30. Epub 2006 Nov 2 OSAS and Coronary Artery Disease • Can CAD worsen OSAS? • Prospective cohort study of 2721 patients (mean age 62 years) without known cardiovascular disease followed for 5 years (13) • Polysomnogram perfomed at baseline and after 5 years (13) Chami HA et al, Circulation, 2011 Mar 29;123(12):1280-6. Epub 2011 Mar 14 Chami HA et al, Circulation, 2011 Mar 29;123(12):1280-6. Epub 2011 Mar 14 Key Points • OSAS increases morbidity and mortality due to CAD (especially severe OSAS) • CAD can also worsen OSAS • CPAP may reduce adverse events related to CAD OSAS and Arrhythmias Bradycardia, Asystole Tachyarrhythmias Atrial Fibrillation Ventricular tachycardia OSAS and Cardiac Arrhythmias • Observational study of 228 patients with RDI ≥ 30/hour compared to 338 controls with RDI ≤ 5/hour (14) • OSAS patients had a higher prevalence of nocturnal arrhythmias (14) Mehra R et al, AJRCCM, 2006 Apr 15;173(8):910-6. Epub 2006 Jan 19 Mehra R et al, AJRCCM, 2006 Apr 15;173(8):910-6. Epub 2006 Jan 19 OSAS and Cardiac Arrhythmias • Bradycardia and asytole are the most prominent and significant rhythm disturbances • OSAS can cause bradyarrhythmias during waking hours (15) (15) Garrigue S et al, Circulation, 2007 Apr 3;115(13):1703-9. Epub 2007 Mar 12 OSAS ↓SO2 ↑pCO2 ↓pH ↑Vagal tone Bradyarrhythmias Mueller’s maneuver OSAS and Atrial Fibrillation • Prevalence of atrial fibrillation (AF) in OSAS patients is low but higher than in the general population (14) • Prevalence of OSAS in AF patients is very high (32%82%) (16, 17) • OSAS can be associated with recurrent atrial fibrillation (18) (14) Mehra R et al, AJRCCM, 2006 Apr 15;173(8):910-6. Epub 2006 Jan 19 (16) Porthan KM et al, Chest, 2004 Mar;125(3):879-85 (17) Gami AS et al, Circulation, 2004 Jul 27;110(4):364-7. Epub 2004 Jul 12 (18) Kanagala R et al, Circulation, 2003 May 27;107(20):2589-94. Epub 2003 May 12 OSAS and Cardiac Arrhythmias • CPAP decreases nocturnal ventricular asystole and bradycardia in OSAS patients (19) • Impact of CPAP on other arrhythmias is unknown • Impact of other therapies for OSAS on cardiac arrhythmias is unknown • Long term data on impact of therapy on mortality is lacking (19) Simantirakis EN et al, Eur Heart J, 2004 Jun;25(12):1070-6 Key Points • Patients with nocturnal or daytime arrhythmias and those with pacemakers should undergo evaluation for OSAS OSAS and Heart Failure • Prospective cohort study of 1927 men and 2495 women without baseline heart failure followed for a median of 8.7 years (20) • Baseline polysomnogram performed • Men with severe OSAS had greatest risk of developing heart failure • No increase in heart failure in women (20) Gottlieb DJ et al, Circulation, 2010 Jul 27;122(4):352-60. Epub 2010 Jul 12 Gottlieb DJ et al, Circulation, 2010 Jul 27;122(4):352-60. Epub 2010 Jul 12 OSAS and Heart Failure • Observational study of 700 patients with heart failure revealed a 36% prevalence of OSAS (21) (21) Oldenburg O et al, Eur J Heart Fail, 2007, 9 (3): 251-257. OSAS ↑LV afterload Cor pulmonale CAD Heart Failure Progression ↑Sympathetic tone Heart Failure Fluid retention Airway congestion ↑ AHI Kaneko Y et al, NEJM, 2003 Mar 27;348(13):1233-41 Kaneko Y et al, NEJM, 2003 Mar 27;348(13):1233-41 Key Points • Severe OSAS can cause development of heart failure in men • OSAS can cause progression of heart failure • Heart failure may potentially increase the AHI • CPAP can improve left ventricular ejection fraction in OSAS patients OSAS and Stroke • Prospective cohort study of 5422 individuals without history of stroke (22) • Median follow up for 8.7 years (22) Redline S. et al, AJRCCM, 2010 Jul 15;182(2):269-77 Redline S. et al, AJRCCM, 2010 Jul 15;182(2):269-77 Redline S. et al, AJRCCM, 2010 Jul 15;182(2):269-77 OSAS ↑ BP Inflammation Heart Disease Endothelial dysfunction Stroke Diabetes mellitus Johnson KG et al, J Clin Sleep Med, 2010;6:131 Parra O et al, AJRCCM, 2000;161:375 Key Points • OSAS increases stroke risk • High prevalence of OSAS after stroke • OSAS can lead to early neurologic deterioration after stroke (23) • OSAS improves as stroke improves over time (24) • CPAP treatment for OSAS may improve long term cardiovascular and neurologic outcomes after stroke (25) (23) Iranzo A et al, Neurology, 2002 Mar 26;58(6):911-6 (24) Parra O et al, AJRCCM, 2000;161:375 (25) Parra O et al, Eur Respir J. 37; 1128-1136 Conclusion • OSAS is associated with significant morbidity and mortality due to cardiovascular disease • Early recognition and treatment of OSAS is the key to prevention of adverse cardiovascular consequences