Ral Antic Director Thoracic Medicine Head of Sleep Service Royal Adelaide Hospital Visiting Respiratory and Sleep Physician Alice Springs Hospital
Ral AnticDirector Thoracic Medicine
Head of Sleep ServicepRoyal Adelaide Hospital
Visiting Respiratory and Sleep PhysicianAlice Springs Hospitalp g p
Conflict of Interest
Past member of ResMed Medical BoardPast member of ResMed Medical BoardHonoraria from lectures for Novartis, Boehringer, GlaxoInvestigator in Insomnia Clinical TrialsInvestigator in Insomnia Clinical Trials
To discussSleep
what is normal
Disordered breathing in sleep and its treatment
Sleep and the CVS The connection between sleep apnoea and chronic CV diseasesthe mechanisms by which abnormal sleep leads to cardiac injurythe management
4 key aspects of health4 key aspects of health
Nutrition
Health sleepE ercise Healthy sleepExercise
Mental health/Stress
Risk to health in sleepSl i ‘ i ’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
Classification of Sleep DisordersClassification of Sleep Disorders CSD‐2 SYSTEMAmerican Academy of Sleep Medicine, 2005
Insomniaconditions that are characterized by difficulty initiating or maintaining sleep, or by poor quality sleep
Sleep related breathing disorders
Parasomnias undesirable physical events (movements, behaviours) or experiences (emotions, perceptions, dreams) that occur during entry into Sleep related breathing disorders
abnormal respiration during sleep
Hypersomnias of central originprimary complaint is daytime
dreams) that occur during entry into sleep, within sleep, or during arousals from sleep
Sleep related movement disordersl hprimary complaint is daytime
sleepiness that is not due to disturbed sleep or misaligned circadian rhythms
simple, stereotypic movements that disturb sleep eg Restless Legs Syndrome
Isolated symptoms and normal Circadian rhythm sleep disorders chronic or recurrent sleep disturbance due to misalignment between the environment and an individual's sleep‐wake cycle
Isolated symptoms and normal variants
Other sleep disorders individual s sleep wake cycle
A i ifi bli h l h iA significant public health issue
E l i i b th k l d & it i id Explosion in both knowledge & its incidence in the last 10 years
Sleep creates a risky state
Physiological changes in Sleep
In non‐REM sleep (75‐85% sleep time)Parasympathetic tone increases and sympathetic Parasympathetic tone increases and sympathetic decreases
Decrease in HR, BP, systemic vascular resistance and cardiac outputoutputIncrease in cardiac stabilityDecrease in airway size
lin REM sleepDecrease in parasympathetic tone and increase in sympathetic toney p
Rise in BP, HR
Health is adversely affected by
Insufficient or excessive sleepInsufficient or excessive sleepAcutechronic
Fragmentation of sleepAcute Chronic
Sleep apnoearecurrent, sleep induced, partial or complete collapse of the pharyngeal airway
resulting in sleep fragmentation from arousals, daytime sleepiness, O2 desaturation, autonomic dysfunction and p , , yend‐organ damage
f d b d ( )Severity is quantified by Apnoea‐Hypopnoea Index (AHI)
Prevalence is highPrevalence is high
Pathophysiological influence ofPathophysiological influence of OSA in cardiovascular diseaseCycle of Sleep
ApnoeaHypoxaemiaPleural pressure and intramural pressure changeSympathetic activationy p
ArousalVentilation
Reoxygenation and restoration of mechanics
OSA Heart rate BP and SaOOSA – Heart rate, BP and SaO2
TACHYCARDIA
APNEA APNEAACUTE HYPERTENSIONHYPERTENSION
S O2SaO2
Postulated mechanisms underlying the relationship between sleep apnoea and cardiacPostulated mechanisms underlying the relationship between sleep apnoea and cardiac disease.
Jaffe L M et al. Eur Heart J 2013;34:809-815
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: [email protected]
Obstructive sleep apnoea in epidemicObstructive sleep apnoea – in epidemic proportions nowPrevalence depends on definition
AHI > 5/hddl d d ddl d26 % middle‐aged men and 10 % middle‐aged women.
AHI ≥ 10/hr approximately 10 % of the middle‐aged population have OSA 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, HTe a ,
Signs and symptoms of sleep apnea
These are pointers to sleep apneasnoringh ki / i
ZZchoking/gasping
restless sleep waking unrefreshed
Z ZZ
Z Z
waking unrefresheddaytime sleepinessnocturianocturia
Sleep Study Reportp y pNormal Sleep Apnoea
REMMOV AWK
1234
RW1234
SaO2
100
50
SpO2
100
50
Cn.AOb.AMx.AHypUns
+5+5+5+5+5
Cn.AOb.AMx.AHypUnsRERA
+5+5+5+5+5+5
Main indices Apnea Hypopnea Index (AHI)
+5+5
02 desaturation index (ODI)
Effects of obstructive sleep apnoea on pulmonary and nervous systems. p p p y y
Jaffe L M et al. Eur Heart J 2013;34:809-815
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: [email protected]
HypertensionCross sectional, longitudinal and prospective studies show strong rel between OSA & HT, independent of confoundersLoss of nocturnal BP dippingLoss of nocturnal BP dippingCycle of sleep disturbance causes sympathetic overdrive and HTResistant HT correlated with hyper‐aldosteronism which promotes accumulation of fluid in the neck when supine
d OSA Bl ki thi i OSA d HTand worsens OSA. Blocking this improves OSA and HT
Hypertension and OSAThe Sleep Heart Health Study (Nieto et al., 2000) demonstrated:
i i b h i d OSA an association between hypertension and OSA independent of age, obesity and other known confounding factorsgprevalence of hypertension increased with increasing AHI values.
OSA Circadian Rhythm of BP in Controls & OSA
From: Davies: Thorax, Volume 55(9).September 1, 2000.736-740
Hypertension and OSA
l ( ) f d h h k f d lVentura et al. (2004) found higher risk of cardiovascular complications associated with non‐dipping independent of daytime BP.y
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 1 3 ‐ 6 0)Systolic BP 3.6 mmHg higher (95% CI 1.3 6.0)Diastolic BP 1.2 mmHg higher (95% CI 0.3 ‐ 3.3)
Risk of hypertension increases with increasing AHI:Risk of hypertension increases with increasing AHI:AHI 30 : OR 3.15 (95% CI 1.75 ‐ 5.67)AHI 15 : OR 1.78 (95% CI 1.32 ‐ 2.38)
AHI 5: OR 1.21 (95% CI 1.10 ‐ 1.34)
Coronary artery disease (CAD) & acuteCoronary 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
ArrhythmiaOSA associated with hypoxaemia autonomic derangements and 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 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 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 – nocturnal p y yasystole, brady‐arrhythmia, AV nodal block SVT and non‐sustained VT and malignant ventricular arrhythmias
nCPAP decreases rates of these arrhythmias
In patients with OSA and ArrhythmiasSinus arrhythmia is common, esp in REM sleepAbnormal rhythms are more common than with no OSA
AF – OR 4.02d ONon‐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 hypoxaemiaAF stronger rel with CSA, Cheyne Stokes breathing and underlying CVDIncrease in nocturnal sudden death in OSA OR 2 57Increase in nocturnal sudden death in OSA – OR 2.57
Sleep Apnea in Heart FailureContributory mechanisms
hypoxaemia, hypercarbia, causing pulmonary vasoconstriction
increase in intra‐thoracic pressure changes from upper airway obstruction
Myocardial wall stress, atrial size increaseyoca d a a s ess, a a s e c easeImpairment in ventricular functionIncreased venous return causing RV distension and compromise in LV fillingg
Combined long term sympathetic overactivity from OSA and HFMyocyte apoptosis, B adrenoceptor down regulation, decreased y y p p , p g ,HR variability, arrhythmias and increased mortality rate
Heart FailureOSA 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
H f il d b OSA d CSAHeart 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 ? whyOSA ? why
Sleep Apnoea – Central ( Cheyne Stokes Respiration )
Decreased ventilatory drive
Heart failure, stroke, drugs
Enhanced chemoreceptor sensitivity +/‐ prolonged circulation time
„In summary, although CSA has been associated withincreased mortality in heart failure patients, a causal role for
CSA in the morbidity and mortality of heart failure awaitsmore definitive evidence. A number of treatment strategiesfor CSA have been tested, but presently none is ideal with
t t b th ffi d t l h il blrespect to both efficacy and tolerance, nor has any availabletherapy been demonstrated to improve survival.“
Cardiovascular Effects of Sleep ApnoeaMild-Mod OSA CPAP treated OSASevere 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. 2005 Mar 19-25;365(9464):1046-53.
Linked epidemicsObesity, Metabolic Syndrome and Sleep Apnoea
Incidence and prevalence of Sleep Apnoea is rising as we speak
The Weight of the MatterThe Weight of the Matter
10% increase in weight predicted 6-fold increase in odds of developing moderate to severe OSA (AHI≥15)
Peppard 2003
moderate to severe OSA (AHI≥15)
Therapy with nCPAP is very cost effective
Condition/Treatment Cost per QALY
CPAP for moderate-severe OSA $3000-5000 /QALY gained
Condition/Treatment Cost per QALY
Treatment for Erectile Dysfunction $6,400/QALY
*Physician Counseling for Smoking $7,200/QALY
Total Hip Replacement $9 900/QALYTotal Hip Replacement $9,900/QALY*Outreach for Flu and Pneumonia $13,000/QALY
Treatment of Major Depression $20,000/QALY
Gastric Bypass Surgery $20 000/QALYGastric Bypass Surgery $20,000/QALY
Treatment for Osteoporosis $38,000/QALY
*Screening For Colon Cancer $40,000/QALYImplantable Cardioverter Defibrillator $75 000/QALYImplantable Cardioverter Defibrillator $75,000/QALY
Lung-Volume Reduction Surgery $98,000/QALY
Tight Control of Diabetes $154,000/QALY
*Treating Elevated Cholesterol ( + 1 risk factor) $200 000/QALYTreating Elevated Cholesterol ( + 1 risk factor) $200,000/QALY
Resuscitation After Cardiac Arrest $270,000/QALY
Left Ventricular Assist Device $900,000/QALY
Evidence for a causal link between OSA and cardio‐vascular disease remains circumstantial
Studies of intermediate markers small subject numbers, short follow‐up (months)j , p ( )
Population and clinic studies positive associations between OSA and CV diseasepositive associations between OSA and CV disease
NO large, long‐term RCTs exploring link between OSA and “hard” cardiovascular endpointshard cardiovascular endpoints
The SAVE trialThe SAVE trial
l ( ) lMulticentre RCT (n=5000) CPAP versus usual care (2008‐2013)
P ti t ith d t d CV di PLUS d tPatients with documented CV disease PLUS moderate‐severe OSA
“Hard” CV outcomes –myocardial infarction stroke Hard CV outcomes myocardial infarction, stroke, sudden death, hospital admission for TIA or unstable angina
SITES
1 site
5 sites, 3 initiated2 ti t
1 site
46 sites, 1164 patients
8 sites, 67 patients
1 site initiated 2 patients
p12 sites,
184 patients 15 sites
5 sites, 87 patients
SummarySl lit d tit i f d t l t h lthSleep quality and quantity is fundamental to health
Sleep disordered breathing is common It causes 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