20 th Annual Advances in Diagnosis and Treatment of Sleep Apnea and Snoring Financial Disclosure February 14-15, 2014 • Member of medical advisory board of Zephyr Cardiovascular Sleep Technologies Consequences of OSA Samuel T. Kuna, MD Center for Sleep and Respiratory Neurobiology University of Pennsylvania and Pulmonary, Critical Care & Sleep Section Philadelphia VAMC Hypnogram Hypnogram Respiratory Events Respiratory Events SaO 2 SaO 2 Body Position Body Position CPAP started What intervention did patient receive? 180 Blood Pressure 70 10-16-13 12-16-13 1-13-14 Intervention ?
Acute hemodynamic effects of OSA Day-night pattern of sudden death in OSA EEG EOG ECG FA Press (mm HG) PA Press (mm HG) SaO 2 (%) Abd Resp Time Code Motta et al. Ann Intern Med 89: 454-458, 1978 Gami et al. NEJM 352:1206-14, 2005 Association of nocturnal arrhythmias Increased mortality in OSA Wisconsin Sleep Cohort Study with sleep disordered breathing Total Sample Sample Excluding CPAP Treated Participants • Nested group-matched exposed and non-exposed design • Group frequency matching to obtain covariate AHI < 5 distributions of age, sex, race/ethnicity and BMI AHI < 5 AHI 5-15 AHI 5-15 % Surviving AHI 5-30 AHI 5-30 AHI < 5 AHI ≥ 30 Odds 95% CI Ratio n = 338 n = 228 Atrial fibrillation 0.9% 4.8% 4.02 1.03 – 15.74 AHI ≥ 30 Non-sustained 1.2% 5.3% 3.40 1.03 – 11.20 AHI ≥ 30 ventricular tach Complex vent- 14.5% 25.0% 1.74 1.11 – 2.74 Years of Follow-up ricular ectopy Adjusted HR (95% CI) for CV mortality in people with severe OSA who had not used CPAP versus people without SDB was 5.2 (1.4,19.2). Mehra et al. AJRCCM 173:910-6, 2006 Young et al. Sleep 31:1071-8, 2008 OSA and incident CVD: the SHHS OSA and incident stroke in males: The Sleep Heart Health Study Coronary Heart Disease - free survival by AHI category - Men Men 40 to 70 yrs old with AHI ≥ 30 were 68% more likely to develop coronary heart disease than those AHI <4.1 with AHI < 5. AHI 4.1- 9.5 AHI 9.5-19.1 Chronic Heart Failure – free survival by AHI category - Men Men with AHI ≥ 30 were 58% more likely to develop heart AHI >19.1 failure than those with AHI < 5 Follow-up (years) Redline et al. AJRCCM 182:269-77, 2010 Gottlieb et al. Circ 2010;22;352-60 Follow-up (years
OSA and incident stroke: Cardiovascular outcomes The Sleep Heart Health Study with or without PAP treatment • Compared to men in the lowest sleep apnea quartile, men with moderately severe OSA p = 0.0012 had an almost 3-fold increased risk of ischemic stroke. • The risk of stroke in men increased 6% with every unit increase in baseline AHI from 5 to 25 events/hr. • In women, increased risk of stroke was only observed for AHI > 25 events/hr. Redline et al. AJRCCM 182:269-77, 2010 Marin et al. Lancet 365:1046-53, 2005 Does sleep apnea cause OSAS cardiovascular disease? Intermittent Hypoxia & Inflammation ↑ FFA Sleep Fragmentation Obesity HTN Sleep ↑ Sympathetic ↑ Oxidative Apnea Activity Stress Insulin Resistance Male CAD Gender Glucose Dyslipidemia Dyslipidemia Hypertension Hypertension Endothelial Intolerance Dysfunction Age CHF Atherosclerosis Arterial Stiffening LV Hypertrophy CARDIOVASCULAR DISEASE Atherosclerotic plaques only in mice on both OBESITY high fat diet and chronic intermittent hypoxia OSAS Normal diet; Normoxia Normal diet; CIH Intermittent Hypoxia & ↑ FFA Inflammation Sleep Fragmentation ↑ Sympathetic ↑ Oxidative Activity Stress Insulin Resistance High cholesterol: Normoxia High cholesterol diet: CIH Glucose Dyslipidemia Dyslipidemia Hypertension Hypertension Endothelial Intolerance Abnormalities Atherosclerosis Arterial Stiffening LV Hypertrophy Savransky et al. AJRCCM 2007;175: 1290 CARDIOVASCULAR DISEASE
OBESITY Association of untreated OSA with risk OSAS of incident hypertension Intermittent Hypoxia & ↑ FFA Inflammation Sleep Fragmentation ↑ Sympathetic ↑ Oxidative Activity Stress Insulin Resistance Glucose Dyslipidemia Dyslipidemia Hypertension Hypertension Endothelial Intolerance Abnormalities Atherosclerosis Arterial Stiffening LV Hypertrophy CARDIOVASCULAR DISEASE Marin et al. JAMA 2012; 307:2169. Change in body weight (kg) Sleep-disordered breathing and HTN Per protocol analysis The Sleep Heart Health Study Intent ‐ to ‐ treat (Compliant subjects) * * * * * * * * Week 8 Week 24 Week 8 Week 24 * P < 0.0001 vs. baseline P = NS for W vs. CPAP + WL at all time points O’Connor et al. AJRCCM 2009; 179:1159–1164 P < 0.0001 CPAP vs either WL or CPAP + WL at all time points
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