Download Ral Antic Director Thoracic Medicine Head of Sleep

Ral Antic
Director Thoracic Medicine
Head of Sleep Service
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Royal Adelaide Hospital
Visiting Respiratory and Sleep Physician
Alice Springs Hospital
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Conflict of Interest
y Past member of ResMed Medical Board
y Honoraria from lectures for Novartis, Boehringer, Glaxo
y Investigator in Insomnia Clinical Trials
To discuss
y Sleep y what is normal
y Disordered breathing in sleep and its treatment
y Sleep and the CVS y The connection between sleep apnoea and chronic CV diseases
y the mechanisms by which abnormal sleep leads to cardiac injury
y the management
4 key aspects of health
4 key aspects of health
Nutrition
E ercise
Exercise
Health sleep
Healthy
Mental health/Stress
Risk to health in sleep
y Sleep is ‘restorative’
Sl i ‘
i ’
y In sleep there is a downturn in activity of all organs y This is needed for ongoing health
y This state can be destabilised by factors, conditions or pre‐existing diseases y This impairs homeostasis and creates a risk to the development of disease
Classification of Sleep Disorders
Classification of Sleep Disorders CSD‐2 SYSTEM
American Academy of Sleep Medicine, 2005 y Insomnia
y conditions that are characterized by difficulty initiating or maintaining sleep, or by poor quality sleep
y Sleep related breathing disorders
y abnormal respiration during sleep
y Hypersomnias of central origin
y primary complaint is daytime sleepiness that is not due to disturbed sleep or misaligned circadian rhythms y Circadian rhythm sleep disorders y chronic or recurrent sleep disturbance due to misalignment between the environment and an individual's sleep‐wake cycle individual
s sleep wake cycle y Parasomnias y undesirable physical events (movements, behaviours) or experiences (emotions, perceptions, dreams) that occur during entry into sleep, within sleep, or during arousals from sleep y Sleep related movement disorders
l
h
y simple, stereotypic movements that disturb sleep eg Restless Legs Syndrome
y Isolated symptoms and normal variants y Other sleep disorders A i ifi
A significant public health issue
bli h l h i
Explosion in both knowledge & its incidence E
l i i b th k
l d & it i id
in the last 10 years
Sleep creates a risky state
Physiological changes in Sleep
y In non‐REM sleep (75‐85% sleep time)
y Parasympathetic tone increases and sympathetic decreases
y
y
y
Decrease in HR, BP, systemic vascular resistance and cardiac output
Increase in cardiac stability
Decrease in airway size
y in REM sleep
l
y Decrease in parasympathetic tone and increase in y p
sympathetic tone
y
Rise in BP, HR
Health is adversely affected by
y Insufficient or excessive sleep
y Acute
y chronic
y Fragmentation of sleep
y Acute y Chronic
The Upper
pp Airway
y
Sleep apnoea
y recurrent, sleep induced, partial or complete collapse of the pharyngeal airway
y resulting in sleep fragmentation from arousals, daytime sleepiness, O2 desaturation, autonomic dysfunction and p
,
,
y
end‐organ damage
y Severity is quantified by Apnoea‐Hypopnoea Index (AHI)
f db
d (
)
y Prevalence is high
Pathophysiological influence of
Pathophysiological influence of OSA in cardiovascular disease
Cycle of Sleep
y Apnoea
y
y
y
Hypoxaemia
Pleural pressure and intramural pressure change
Sympathetic activation
y p
y Arousal
y Ventilation
y
Reoxygenation and restoration of mechanics OSA Heart rate, BP and SaO
Heart rate BP and SaO2
OSA –
TACHYCARDIA
ACUTE
HYPERTENSION
S O2
SaO2
APNEA
APNEA
Postulated 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 epidemic in epidemic
Obstructive sleep apnoea –
proportions now
Prevalence depends on definition
y AHI > 5/h
y
26 % middle‐aged men and 10 % middle‐aged women.
ddl
d
d
ddl
d
y AHI ≥ 10/hr y
approximately 10 % of the middle aged population have OSA approximately 10 % of the middle‐aged population have OSA (1993)
y AHI >20 in 25% of adult males in North West Adelaide ( 2011))
y AHI >20 in 40‐70% with end organ damage – cardiac, renal, HT
e a,
Investigation and therapy
I
i i d h
Signs and symptoms of sleep apnea
These are pointers to sleep apnea
¾
¾
¾
¾
¾
¾
snoring
choking/gasping
h ki /
i
restless sleep waking unrefreshed
daytime sleepiness
nocturia
Z
Z
ZZZ
Z
Cardiovascular Effects of Sleep
Cardiovascular Effects of Sleep Apnea
Home study
Sleep Study Report
p
y p
Normal
Sleep Apnoea
REM
MOV AWK
1
2
3
4
R
W
1
2
3
4
100
100
SaO2
SpO2
50
50
Cn.A
Ob.A
Mx.A
Hyp
Uns
RERA
+5
Cn.A
+5
+5
Ob.A
+5
Mx.A
+5
Hyp
+5
Uns
+5
+5
+5
+5
+5
+5
+5
Main indices
Apnea Hypopnea Index (AHI)
02 desaturation index (ODI)
Sleep apneas go on and on, and on…. 20 minute
min te recording
An Australian Invention
Prof. Colin Sullivan
University of Sydney, 1981
The mechanisms of damage
The mechanisms of damage
Effects of obstructive sleep
on pulmonary
p apnoea
p
p
y and nervous systems.
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]
Hypertension
y Cross sectional, longitudinal and prospective studies show strong rel between OSA & HT, independent of confounders
y Loss of nocturnal BP dipping
y Cycle of sleep disturbance causes sympathetic overdrive and HT
y 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
d OSA Bl ki thi i
OSA d HT
Hypertension and OSA
y The Sleep Heart Health Study (Nieto et al., 2000) demonstrated:
y an association between hypertension and OSA i i b
h
i d OSA independent of age, obesity and other known confounding factors
g
y prevalence 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
y and can actually lead to nocturnal hypertension.
Hypertension and OSA
Ventura et al. (2004) found higher risk of cardiovascular l (
)f
dh h
k f
d
l
complications associated with non‐dipping independent of daytime BP.
y
Wisconsin Sleep Cohort Study
y BP increases linearly with increasing AHI (p = .003)
At AHI 15 (vs 0):
y Systolic BP 3.6 mmHg higher (95% CI 1.3 Systolic BP 3 6 mmHg higher (95% CI 1 3 ‐ 6.0)
6 0)
y Diastolic BP 1.2 mmHg higher (95% CI 0.3 ‐ 3.3)
y Risk of hypertension increases with increasing AHI:
AHI 30 :
AHI 15 : AHI 5: OR 3.15 (95% CI 1.75 ‐ 5.67)
OR 1.78 (95% CI 1.32 ‐ 2.38)
OR 1.21 (95% CI 1.10 ‐ 1.34)
Coronary artery disease (CAD) & acute
Coronary artery disease (CAD) & acute coronary syndrome (ACS)
y Correlation between CAD, ACS & OSA well established – 65% admitted for MI have OSA and carry poor prognosis
y 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%)
y Refractory nocturnal angina has higher rate of OSA, occurs at the same time and is reduced with nCPAP
y Whilst treatment of OSA has not been shown to reverse progression of CAD, it might retard it and can decrease new events
y 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
Arrhythmia
y OSA associated with hypoxaemia, autonomic derangements and OSA associated with hypoxaemia autonomic derangements and cardiac structural changes all which predispose to arrhythmia
y Cross sectional studies of SA show prevalence of 43 Cross sectional studies of SA show prevalence of 43 ‐ 73% in those with AF, and excess CAD and CSA +
y 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
y SA esp
p with heart failure linked with other dysrhythmias –
y y
nocturnal asystole, brady‐arrhythmia, AV nodal block SVT and non‐sustained VT and malignant ventricular arrhythmias
y nCPAP decreases rates of these arrhythmias
In patients with OSA and Arrhythmias
y Sinus arrhythmia is common, esp in REM sleep
y Abnormal rhythms are more common than with no OSA
y AF
– OR 4.02
y Non‐sustained VT
d
– OR 3.40
O
y Complex vent ectopics in severe OSA (bigeminy, trigeminy, quadrigeminy) even adjusting for other risk factors – OR 1.74
y There is a dose‐response relationship between increasing severity OSA and arrhythmia y and y CVE has stronger rel to OSA and hypoxaemia
y AF stronger rel with CSA, Cheyne Stokes breathing and underlying CVD
y Increase in nocturnal sudden death in OSA – OR 2.57
OR 2 57
Sleep Apnea in Heart Failure
Contributory mechanisms
y hypoxaemia, hypercarbia, causing pulmonary vasoconstriction
y increase in intra‐thoracic pressure changes from upper airway obstruction
y Myocardial wall stress, atrial size increase
yoca d a a s ess, a a s e c ease
y Impairment in ventricular function
y Increased venous return causing RV distension and compromise g
in LV filling
y Combined long term sympathetic overactivity from OSA and HF
y
Myocyte
y y apoptosis, B adrenoceptor
p p
,
p down regulation, decreased g
,
HR variability, arrhythmias and increased mortality rate
Heart Failure
y OSA in 47‐76%
y 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
y Heart failure can cause and exacerbate OSA and CSA
H
f il d b OSA d CSA
y CSR carries poor prognosis in HF
y Diastolic dysfunction is highly correlated with sleep disordered breathing – 70% SA in HF with preserved ejection fraction, mainly OSA ? why
Sleep Apnoea – Central ( Cheyne Stokes Respiration )
y Decreased ventilatory drive
y Heart failure, stroke, drugs
y Enhanced chemoreceptor sensitivity +/‐ prolonged circulation time
Cheyne-Stokes respiration
n=32
32
n=56
Javaheri 2007
„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
respectt to
t both
b th efficacy
ffi
and
d tolerance,
t l
nor has
h any available
il bl
therapy been demonstrated to improve survival.“
Teschler H et. al; AJRCCM 2001
b
/
f
OSA better 3/12 after CVA
Parra AMJRCC 2000
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. 2005 Mar 19-25;365(9464):1046-53.
Linked epidemics
y Obesity, Metabolic Syndrome and Sleep Apnoea
y Incidence and prevalence of Sleep Apnoea is rising as we speak
The Weight of the Matter
„
10% increase in weight predicted 6fold increase in odds of developing
moderate to severe OSA (AHI≥15)
Peppard 2003
Therapy with nCPAP is very cost effective
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/QALY
$9,900/QALY
*Outreach for Flu and Pneumonia
$13,000/QALY
Treatment of Major Depression
$20,000/QALY
Gastric Bypass Surgery
$20 000/QALY
$20,000/QALY
Treatment for Osteoporosis
$38,000/QALY
*Screening For Colon Cancer
$40,000/QALY
Implantable Cardioverter Defibrillator
$75 000/QALY
$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/QALY
$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
y Studies of intermediate markers y small subject numbers, short follow‐up (months)
j
,
p(
)
y Population and clinic studies y positive associations between OSA and CV disease
y NO large, long‐term RCTs exploring link between OSA and “hard” cardiovascular endpoints
hard cardiovascular endpoints
The SAVE trial
The SAVE trial
y Multicentre RCT (n=5000) CPAP versus usual care l
(
)
l
(2008‐2013)
y Patients with documented CV disease PLUS moderate‐
P ti t ith d
t d CV di
PLUS d t
severe OSA y “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 initiated
2 patients
ti t
1 site initiated
46 sites,
1164 patients
8 sites,
patients
67 p
15 sites
12 sites,
184 patients
5 sites,
87 patients
Summary
y Sleep quality and quantity is fundamental to health
Sl lit d tit i f d
t l t h lth
y Sleep disordered breathing is common. It causes Sleep disordered breathing is common It causes substantial morbidity and mortality
y OSA is one of the important risk factors to the cardiovascular system y That risk is reduced by its control with nCPAP
y Definitive RCT awaited in a number of areas
Recent reviews
Importance and management of chronic sleep apnoea in p
g
p p
Cardiology, Jaffe et al, European Heart Journal 2013, 34,809‐815
Obstructive Sleep Apnoea in adults, Usmani et al Post Grad Medicine 2013, 89: 148‐156