Cardiovascular Sleep Technologies Consequences of OSA Samuel T. - - PDF document

Samuel T. Kuna, MD

Center for Sleep and Respiratory Neurobiology University of Pennsylvania and Pulmonary, Critical Care & Sleep Section Philadelphia VAMC

20th Annual Advances in Diagnosis and Treatment of Sleep Apnea and Snoring February 14-15, 2014

Cardiovascular Consequences of OSA

Financial Disclosure

• Member of medical advisory board of Zephyr

Sleep Technologies

Hypnogram Respiratory Events Body Position SaO2 Hypnogram Respiratory Events Body Position SaO2 CPAP started Intervention ?

What intervention did patient receive?

Blood Pressure

10-16-13 12-16-13 1-13-14 180 70

Day-night pattern of sudden death in OSA

Gami et al. NEJM 352:1206-14, 2005

Acute hemodynamic effects of OSA

FA Press

(mm HG)

PA Press

(mm HG)

EEG EOG ECG SaO2 (%) Abd Resp Time Code

Motta et al. Ann Intern Med 89: 454-458, 1978

Association of nocturnal arrhythmias with sleep disordered breathing

Mehra et al. AJRCCM 173:910-6, 2006 AHI < 5 n = 338 AHI ≥ 30 n = 228 Odds Ratio 95% CI Atrial fibrillation 0.9% 4.8% 4.02 1.03 – 15.74 Non-sustained ventricular tach 1.2% 5.3% 3.40 1.03 – 11.20 Complex vent- ricular ectopy 14.5% 25.0% 1.74 1.11 – 2.74

• Nested group-matched exposed and non-exposed design
• Group frequency matching to obtain covariate

distributions of age, sex, race/ethnicity and BMI

Increased mortality in OSA

Wisconsin Sleep Cohort Study

Young et al. Sleep 31:1071-8, 2008 % Surviving Years of Follow-up Total Sample Sample Excluding CPAP Treated Participants

AHI < 5 AHI 5-15 AHI 5-30 AHI ≥ 30 AHI < 5 AHI 5-15 AHI 5-30 AHI ≥ 30

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).

OSA and incident CVD: the SHHS

Follow-up (years Coronary Heart Disease - free survival by AHI category - Men Chronic Heart Failure – 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 with AHI < 5. Men with AHI ≥ 30 were 58% more likely to develop heart failure than those with AHI < 5 Gottlieb et al. Circ 2010;22;352-60

OSA and incident stroke in males: The Sleep Heart Health Study

AHI <4.1 AHI 4.1- 9.5 AHI >19.1 AHI 9.5-19.1 Redline et al. AJRCCM 182:269-77, 2010 Follow-up (years)

OSA and incident stroke: The Sleep Heart Health Study

• Compared to men in the lowest sleep apnea

quartile, men with moderately severe OSA 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
• bserved for AHI > 25 events/hr.

Redline et al. AJRCCM 182:269-77, 2010

p = 0.0012

Marin et al. Lancet 365:1046-53, 2005

Cardiovascular outcomes with or without PAP treatment

Sleep Apnea

Obesity Male Gender Age HTN CAD CHF

Does sleep apnea cause cardiovascular disease?

OSAS ↑ FFA Inflammation ↑ Sympathetic Activity ↑ Oxidative Stress Glucose Intolerance Dyslipidemia Hypertension Endothelial Dysfunction CARDIOVASCULAR DISEASE Arterial Stiffening LV Hypertrophy Atherosclerosis Intermittent Hypoxia & Sleep Fragmentation Insulin Resistance Dyslipidemia Hypertension

Atherosclerotic plaques only in mice on both high fat diet and chronic intermittent hypoxia

Savransky et al. AJRCCM 2007;175: 1290

Normal diet; Normoxia Normal diet; CIH High cholesterol diet: CIH High cholesterol: Normoxia OBESITY OSAS ↑ FFA Inflammation ↑ Sympathetic Activity ↑ Oxidative Stress Glucose Intolerance Dyslipidemia Hypertension Endothelial Abnormalities CARDIOVASCULAR DISEASE Arterial Stiffening LV Hypertrophy Atherosclerosis Intermittent Hypoxia & Sleep Fragmentation Insulin Resistance Dyslipidemia Hypertension

OBESITY OSAS ↑ FFA Inflammation ↑ Sympathetic Activity ↑ Oxidative Stress Glucose Intolerance Dyslipidemia Hypertension Endothelial Abnormalities CARDIOVASCULAR DISEASE Arterial Stiffening LV Hypertrophy Atherosclerosis Intermittent Hypoxia & Sleep Fragmentation Insulin Resistance Dyslipidemia Hypertension

Marin et al. JAMA 2012; 307:2169.

Association of untreated OSA with risk

• f incident hypertension

Sleep-disordered breathing and HTN The Sleep Heart Health Study

O’Connor et al. AJRCCM 2009; 179:1159–1164

Change in body weight (kg)

Intent‐to‐treat Per protocol analysis (Compliant subjects) * P < 0.0001 vs. baseline P = NS for W vs. CPAP + WL at all time points P < 0.0001 CPAP vs either WL or CPAP + WL at all time points

Week 8 Week 24 Week 8 Week 24

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