Ral Antic Director Thoracic Medicine Head of Sleep Service Royal Adelaide Hospital. Visiting Respiratory and Sleep Physician Alice Springs Hospital
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1 Ral Antic Director Thoracic Medicine Head of Sleep Service Royal Adelaide Hospital Visiting Respiratory and Sleep Physician Alice Springs Hospital
2 Conflict of Interest Past member of ResMed Medical Board Honoraria from lectures for Novartis, Boehringer, Glaxo Investigator in Insomnia Clinical Trials
3 To discuss Sleep what is normal Disordered breathing in sleep and its treatment Sleep and the CVS The connection between sleep apnoea and chronic CV diseases the mechanisms by which abnormal sleep leads to cardiac injury the management
4 4 key aspects of health Nutrition Exercise Healthy sleep Mental health/stress
5 Risk to health in sleep Sleep is restorative In sleep there is a downturn in activity of all organs This is needed for ongoing health This state can be destabilised by factors, conditions or pre existing diseases This impairs homeostasis and creates a risk to the development of disease
6 Classification of Sleep Disorders CSD 2 SYSTEM American Academy of Sleep Medicine, 2005 Insomnia conditions that are characterized by difficulty initiating or maintaining sleep, or by poor quality sleep Sleep related breathing disorders abnormal respiration during sleep Hypersomnias of central origin primary complaint is daytime sleepiness that is not due to disturbed sleep or misaligned circadian rhythms Circadian rhythm sleep disorders chronic or recurrent sleep disturbance due to misalignment between the environment and an individual's sleep wake cycle Parasomnias undesirable physical events (movements, behaviours) or experiences (emotions, perceptions, dreams) that occur during entry into sleep, within sleep, or during arousals from sleep Sleep related movement disorders simple, stereotypic movements that disturb sleep eg Restless Legs Syndrome Isolated symptoms and normal variants Other sleep disorders
7 A significant ifi public health h issue Explosion in both knowledge & its incidence id in the last 10 years Sleep creates a risky state
8 Physiological changes in Sleep In non REM sleep (75 85% sleep time) Parasympathetic tone increases and sympathetic decreases Decrease in HR, BP, systemic vascular resistance and cardiac output Increase in cardiac stability Decrease in airway size in REM sleep Decrease in parasympathetic tone and increase in sympathetic tone Rise in BP, HR
9 Health is adversely affected by Insufficient or excessive sleep Acute chronic Fragmentation of sleep Acute Chronic
10 The Upper Airway
11 Sleep apnoea recurrent, sleep induced, partial or complete collapse of the pharyngeal airway resulting in sleep fragmentation from arousals, daytime sleepiness, O2 desaturation, autonomic dysfunction and end organ damage Severity is quantified dby Apnoea Hypopnoea Index (AHI) Prevalence is high
12 Pathophysiological influence of OSA in cardiovascular disease Cycle of Sleep Apnoea Hypoxaemia Pleural pressure and intramural pressure change Sympathetic activation Arousal Ventilation Reoxygenation and restoration of mechanics
13 OSA Heart rate, BP and SaO 2 TACHYCARDIA ACUTE HYPERTENSION APNEA APNEA SaO2
14 Postulated mechanisms underlying the relationship between sleep apnoea and cardiac disease. Jaffe L M et al. Eur Heart J 2013;34: Published on behalf of the European Society of Cardiology. All rights reserved. The Author For permissions please journals.permissions@oup.com
15 Obstructive sleep apnoea in epidemic proportions now Prevalence depends on definition AHI > 5/h 26 % middle aged d men and 10 % middle aged d women. AHI 10/hr approximately 10 % of the middle aged population have OSA (1993) AHI >20 in 25% of adult males in North West Adelaide ( 2011) AHI >20 in 40 70% with end organ damage cardiac, renal, HT
16 Investigation i and therapy
17 Signs and symptoms of sleep apnea These are pointers to sleep apnea snoring choking/gasping i restless sleep waking unrefreshed daytime sleepiness nocturia Z Z Z Z Z Z
18 Cardiovascular Effects of Sleep Apnea
19 Home study
20 Sleep Study Report Normal Sleep Apnoea R W REM MOV AWK SpO2 SaO Cn.A Ob.A Mx.A Hyp Uns RERA Cn.A Ob.A Mx.A Hyp Uns Main indices Apnea Hypopnea Index (AHI) 02 desaturation index (ODI)
21 Sleep apneas go on and on, and on. 20 minute recording
22 An Australian Invention Prof. Colin Sullivan University of Sydney, 1981
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26 The mechanisms of damage
27 Effects of obstructive sleep apnoea on pulmonary and nervous systems. Jaffe L M et al. Eur Heart J 2013;34: Published on behalf of the European Society of Cardiology. All rights reserved. The Author For permissions please journals.permissions@oup.com
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29 Hypertension Cross sectional, longitudinal and prospective studies show strong rel between OSA & HT, independent of confounders Loss of nocturnal BP dipping Cycle of sleep disturbance causes sympathetic overdrive and HT Resistant HT correlated with hyper aldosteronism which promotes accumulation of fluid in the neck when supine and worsens OSA. Blocking this improves OSA and HT
30 Hypertension and OSA The Sleep Heart Health Study (Nieto et al., 2000) demonstrated: an association i between hypertension and OSA independent of age, obesity and other known confounding factors prevalence of hypertension increased with increasing AHI values.
31 OSA Circadian Rhythm of BP in Controls & OSA From: Davies: Thorax, Volume 55(9).September 1,
32 Hypertension and OSA and can actually lead to nocturnal hypertension.
33 Hypertension and OSA Ventura et al. (2004)found dhigher h risk of cardiovascular complications associated with non dipping independent of daytime BP.
34 Wisconsin Sleep Cohort Study BP increases linearly with increasing AHI (p =.003) At AHI 15 (vs 0): Systolic BP 3.6 mmhg higher (95% CI ) 6.0) Diastolic BP 1.2 mmhg higher (95% CI ) Risk of hypertension increases with increasing AHI: AHI 30 : OR 3.15 (95% CI ) AHI 15 : OR 1.78 (95% CI ) AHI 5: OR 1.21 (95% CI )
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36 Coronary artery disease (CAD) & acute coronary syndrome (ACS) Correlation between CAD, ACS & OSA well established 65% admitted for MI have OSA and carry poor prognosis OSA when present with successful coronary intervention after ACS was associated with higher mortality (38% vs 9%), increased rate of stent restenosis (24%vs 5%) Refractory nocturnal angina has higher rate of OSA, occurs at the same time and is reduced with ncpap Whilst treatment of OSA has not been shown to reverse progression of CAD, it might retard it and can decrease new events OSA increases blood coagulability, viscosity and increased platelet aggregability, higher levels of clotting factors. This may contribute to CAD progression and in stent thrombus formation
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38 Arrhythmia OSA associated with hypoxaemia, autonomic derangements and cardiac structural changes all which predispose to arrhythmia Cross sectional studies of SA show prevalence of 43 73% in those with AF, and excess CAD and CSA + In OSA > 25% greater risk of AF recurrence after ablation. Treatment with ncpap gives 8 fold improvement in lasting success of ablation SA esp with heart failure linked with other dysrhythmias y nocturnal asystole, brady arrhythmia, AV nodal block SVT and non sustained VT and malignant ventricular arrhythmias ncpap decreases rates of these arrhythmias
39 In patients with OSA and Arrhythmias Sinus arrhythmia is common, esp in REM sleep Abnormal rhythms are more common than with no OSA AF OR 4.02 Non sustained VT OR 3.40 Complex vent ectopics in severe OSA (bigeminy, trigeminy, quadrigeminy) even adjusting for other risk factors OR 1.74 There is a dose response relationship between increasing severity OSA and arrhythmia and CVE has stronger rel to OSA and hypoxaemia AF stronger rel with CSA, Cheyne Stokes breathing and underlying CVD Increase in nocturnal sudden death in OSA OR 2.57
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42 Sleep Apnea in Heart Failure Contributory mechanisms hypoxaemia, hypercarbia, causing pulmonary vasoconstriction increase in intra thoracic pressure changes from upper airway obstruction Myocardial a wall stress, ess,atrial a size increase cease Impairment in ventricular function Increased venous return causing RV distension and compromise in LV filling Combined long term sympathetic overactivity from OSA and HF Myocyte y apoptosis, p B adrenoceptor down regulation, decreased HR variability, arrhythmias and increased mortality rate
43 Heart Failure OSA in 47 76% Complex mechanisms increase in sympathetic tone and heart rate in already failing heart can lead to myocyte injury, cardiac B adrenergic desensitisation and functional and structural abnormalities Heart failure can cause and exacerbate OSA and CSA CSR carries poor prognosis in HF Diastolic dysfunction is highly correlated with sleep disordered breathing 70% SA in HF with preserved ejection fraction, mainly OSA? why
44 Sleep Apnoea Central ( Cheyne Stokes Respiration ) Decreased ventilatory drive Heart failure, stroke, drugs Enhanced chemoreceptor sensitivity +/ prolonged circulation time
45 Cheyne-Stokes respiration
46 n=32 n=56 Javaheri 2007
47 In summary, although CSA has been associated with increased mortality in heart failure patients, a causal role for CSA in the morbidity and mortality of heart failure awaits more definitive evidence. A number of treatment strategies for CSA have been tested, but presently none is ideal with respect tto both efficacy and dtolerance, nor has any available therapy been demonstrated to improve survival.
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49 Teschler H et. al; AJRCCM 2001
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52 OSA better 3/12 after CVA Parra AMJRCC 2000
53 Cardiovascular Effects of Sleep Apnoea Severe OSA Mild-Mod OSA CPAP treated OSA Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet Mar 19-25;365(9464):
54 Linked epidemics Obesity, Metabolic Syndrome and Sleep Apnoea Incidence and prevalence of Sleep Apnoea is rising as we speak
55 The Weight of the Matter 10% increase in weight predicted 6- fold increase in odds of developing moderate to severe OSA (AHI 15) Peppard 2003
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57 Therapy with ncpap is very cost effective CPAP for moderate-severe OSA $ /QALY gained Condition/Treatment Treatment for Erectile Dysfunction *Physician Counseling for Smoking Total Hip Replacement *Outreach for Flu and Pneumonia Treatment of Major Depression Gastric Bypass Surgery Treatment for Osteoporosis *Screening For Colon Cancer Implantable Cardioverter Defibrillator Lung-Volume Reduction Surgery Tight Control of Diabetes *Treating Elevated Cholesterol ( + 1 risk factor) Resuscitation After Cardiac Arrest Left Ventricular Assist Device Cost per QALY $6,400/QALY $7,200/QALY $9,900/QALY900/QALY $13,000/QALY $20,000/QALY $20,000/QALY000/QALY $38,000/QALY $40,000/QALY $75,000/QALY $98,000/QALY $154,000/QALY $200,000/QALY000/QALY $270,000/QALY $900,000/QALY
58 Evidence for a causal link between OSA and cardiovascular disease remains circumstantial Studies of intermediate markers small subject numbers, short follow up (months) Population and clinic studies positive associations between OSA and CV disease NO large, long term RCTs exploring link between OSA and hard cardiovascular endpoints
59 The SAVE trial Multicentre RCT (n=5000) CPAP versus usual care ( ) Pti Patients t with documented d CV disease PLUS moderatesevere OSA Hard CV outcomes myocardial infarction stroke Hard CV outcomes myocardial infarction, stroke, sudden death, hospital admission for TIA or unstable angina
60 SITES 1site 5 sites, 3 initiated 2 patients t 1 site initiated 15 sites 8 sites, 67 patients 46 sites, 1164 patients 12 sites, 184 patients 5 sites, 87 patients
61 Summary Sleep quality and quantity is fundamental to health Sleep disordered breathing is common. It causes substantial morbidity and mortality OSA is one of the important risk factors to the cardiovascular system That risk is reduced by its control with ncpap Definitive RCT awaited in a number of areas
62 Recent reviews Importance and management of chronic sleep apnoea in Cardiology, Jaffe et al, European Heart Journal 2013, 34, Obstructive Sleep Apnoea in adults, Usmani et al Post Grad Medicine 2013, 89:
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