Cardiovascular Disease and
Sleep-Disordered Breathing
Sleep Physician
ResMed Specialist
Waking people up to sleep
Agenda
• Case study – Heart Block and Sleep Apnea
• Sleep Apnea: Definitions and Prevalence
• Cardiovascular Consequences of Sleep Apnea
• Therapeutic outcomes
• Therapeutic options
2 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Case Study
Waking people up to sleep
• 30+ second apnea
(no airflow)
• Abdominal effort
throughout apnea
(obstructive sleep
apnea)
• Oxygen saturation
drops below 80%
• Heart block event
associated with
apnea
Case Study: Heart Block Associated Event Associated with OSA
4 Cardiovascular Disease and Sleep-disordered Breathing © ResMed 2003
Each episode of
heart block is
preceded by an
apneic event
Case study: ECG Trace and Heart Block Events Associated with OSA
5 Cardiovascular Disease and Sleep-disordered Breathing © ResMed 2003
Sleep Apnea:
Definitions and Prevalence
Waking people up to sleep
Overview of Sleep Apnea
•
Sleep Disordered Breathing
(SDB) describes a number of
nocturnal breathing disorders
•
Sleep Apnea is the dominant
type of SDB
– Obstructive sleep apnea (OSA)
– Central sleep apnea (CSA)
•
7 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
OSA and CSA are highly
prevalent in patients with
cardiovascular disease
Sleep Apnea Types
•
Obstructive Sleep Apnea (OSA):
– Apnea with ventilatory efforts due to pharyngeal collapse
– Patient tries to breathe but can’t due to upper airway obstruction
– ~90% of sleep apnea cases1
•
Central Sleep Apnea (CSA):
– Apnea without ventilatory effort due to withdrawal of central drive
– Cheyne-Stokes respiration a subset of CSA
– ~10% of sleep apnea cases1
•
Mixed Sleep Apnea:
– Apnea with central component followed by obstructive component
– Often classified as obstructive sleep apnea
1
Young T, Palta M, et al. The Occurrence of Sleep-Disordered Breathing Among
Middle-Aged Adults. N Eng J Med; 328: 1230-35.
8 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Sleep Apnea Definitions1
Apnea:
Hypopnea:
AHI:
Cessation of Airflow > 10 sec
>50% reduction in airflow for >10 sec
Apnea Hypopnea Index: the number of apneas
and hypopneas per hour of sleep
–Normal:
–Mild:
–Moderate:
–Severe:
Severity Definitions:
Sleep Apnea Syndrome:
1
AHI < 5
AHI 5 – 14
AHI 15 – 30
AHI >30
AHI of > 5 with symptoms.
American Academy of Sleep Medicine, Sleep-Related Breathing Disorders in Adults: Recommendations for Syndrome
Definition and Measurement Techniques in Clinical Research -AASM Task Force. SLEEP 1999;22(5):667-689.
9 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Prevalence in General Population
• Young et al., NEJM, 1993:328:1230-5
– N = 602 (F 250, M 352)
– Age 30-60 years, employed
• AHI>5: mild, moderate, or severe sleep apnea*
– 24% of middle aged men
– 9% of middle aged women
– These patients stop breathing >40 times per night
• AHI>15: moderate or severe sleep apnea
– 15% of middle-aged men
– 5% of middle-aged women
– These patients stop breathing >120 times per night
10 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Prevalence of Sleep Apnea
increases with age
Young T, et al. Predictors of Sleep-Disordered Breathing in Community-Dwelling Adults. Arch Intern Med 2002; 162:
893-900.
11 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Normal Breathing
Nasal airflow
Thorax effort
Abdominal effort
SaO2
Snore
12 Cardiovascular Disease and Sleep-disordered
Sleep-Disordered Breathing
Breathing ©
©ResMed
ResMed 2003
2004
Obstructive Sleep Apnea
•
Most common type of SDB
•
Muscles that control the
tongue and soft palate relax
causing the airway to narrow
and close
•
Patient tries to breathe but
cannot due to airway
obstruction
•
Patient stops breathing for
more than 10 seconds
Normal breathing
Obstructive apnea
13 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Closed
Airway
Obstructive Sleep Apnea (OSA)
14 Cardiovascular Disease and Sleep-disordered
Sleep-Disordered Breathing
Breathing ©
©ResMed
ResMed 2003
2004
Central Sleep Apnea
Normal breathing
Central apnea
Open
Airway
15 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
•
Patient makes no effort to
breathe in thorax nor
abdomen during apnea
•
Patient stops breathing for
more than 10 seconds
•
Typical in severe heart failure
patients
•
May be characterized by
Cheyne-Stokes respiration
(CSR) separated by periods
of apnea or hypopnea
Central Sleep Apnea (CSA)
16 Cardiovascular Disease and Sleep-disordered
Sleep-Disordered Breathing
Breathing ©
©ResMed
ResMed 2003
2004
Cardiovascular
Consequences of
Sleep Apnea
Waking people up to sleep
Apnea
Plunging blood
oxygen
saturation
Negative swings
in intra-thoracic
pressure
Increase in
blood pressure
Surge in sympathetic
nerve activity
Physiological Consequence of Sleep Apnea (Morgan et al. Sleep 1996)
Cardiovascular Disease and Sleep-disordered Breathing
Mechanisms of Sleep Apnea Inducing
Cardiovascular Disease
Mechanisms Discussed in Literature:
•
Hypoxia resulting directly from apnea
•
Negative intra-thoracic pressure from
effort to breathe increases cardiac stress
•
Pulmonary and systemic hypertension
•
Increased sympathetic nerve activity
during arousal (neuro-hormonal surge)
•
Stimulation of inflammatory pathways
•
Endothelial dysfunction
19 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Sleep Apnea and Hypertension
• SDB has a dose-response relationship with
hypertension, independent of all known risk factors
(age, gender, BMI, smoking, alcohol, others)
–
–
–
–
Nieto et al. JAMA 2000 (SHHS n=6132)
Lavie et al. BMJ 2000 (n=2677)
Bixler et al. Arch Intern Med 2000 (n=1741)
Peppard et al. NEJM 2000 (WSCS n=709)
20 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Dose-Response
relationship
between AHI and
risk for developing
hypertension,
independent of
confounding factors
Apnea/Hypopnea Index (AHI)
Sleep Apnea and Odd-ration for Developing Hypertension (Lavie et al. BMJ 2000)
21 Cardiovascular Disease and Sleep-disordered Breathing
Sleep Apnea Prevalence in
Cardiovascular Disease Patients
Drug-Resistant
Hypertension
80%
Congestive Heart
Failure
50%
Atrial Fibrillation
All Hypertension
45%
35%
Logan et al.
J. Hypertension 2001
Javaheri et al.
Circulation 1999
Somers et al.
Circulation 2004
Sjostrom et al.
Thorax 2002
Coronary Artery
Disease
30%
Schafer et al.
Cardiology 1999
Angina
30%
Sanner et al.
Clin Cardiology 2001
22 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Sleep Apnea is an
Identifiable
Cause of
Hypertension
- NIH, JNC7 (2003)
23 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
v
Sleep Apnea and
Coronary Artery Disease
•
>30% of patients with CAD have sleep apnea
•
OSA is an associated with an increased risk of cardiovascular
mortality in patients with CAD with a dose-response relationship
Figure 1. By use of a Poisson
model the death hazard was
calculated as a function of RDI,
current age, and time elapsed
after the intensive care
episode for CAD. The bolded
curve gives the function at the
current age 70 yr and 3 yr after
intensive care. The dotted
curves represent 95% CI.
Peker Y, Hedner J, Kraiczi H,
et al. Am J Respir Crit Care
Med. 2000 Vol. 162. Pp 81-86.
AHI
24 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Therapeutic
Outcomes
Waking people up to sleep
CPAP treats OSA providing a pneumatic
splint to keep the upper airway open
Sullivan et al.
Lancet (1981)
26 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Percent
OSA: Oxygen Desaturation
Before CPAP
100
90
80
70
60
50
40
30
20
10
0
O2 Sat
0
1
2
3
Hours
Sullivan, et al., 1981
27 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
4
5
Percent
OSA: Oxygen Desaturation
After CPAP
100
90
80
70
60
50
40
30
20
10
0
A
O2 Sat
A = Introduction
of CPAP
0
1
2
3
Hours
Sullivan, et al., 1981
28 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
4
5
Control Arm
140
b a s e line
M A P (m m H g )
s ub the ra p e utic nC P A P
120
100
Average 10 mm Hg
reduction in BP
predicts:
80
60
7
15
pm
11
15
pm
3
15
am
7
15
am
Therapeutic Arm
• Coronary artery
disease risk
reduced by 37%
• Stroke risk
reduced by 56%
140
b a s e line
M A P (m m H g)
e ffe c tive nC P A P
120
100
80
60
7 1 5 pm
11 1 5 pm
3 1 5 am
7 1 5 am
Effect of nCPAP on Blood Pressure (Becker et al. Circulation 2003)
29 Cardiovascular Disease and Sleep-disordered Breathing
v
• Average 35%
relative increase
in LVEF
• OSA may have an
adverse effect in
heart failure that
can be
addressed by
CPAP therapy
N=24
Effect of CPAP on LVEF (Kaneko et al. N Engl J Med 2003)
30 Cardiovascular Disease and Sleep-disordered Breathing
Event-free Survival in CAD Patients with
OSA: CPAP Therapy and Control Arms
N=54
Milleron et al. Eur Heart J 2004;25:728
31 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
• 75% five-year survival rate
for CHF patients with
CSA/CSR on CPAP
• 25% five-year survival rate
for CHF patients with
CSA/CSR not on CPAP
CPAP Therapy
n = 64
Comparison of Transplant Free Survival in CHF Patients: CPAP vs Control
(Sin et al. Circulation 2000)
32 Cardiovascular Disease and Sleep-disordered Breathing
Therapeutic
Options
Waking people up to sleep
OSA Therapeutic Methods
• Current:
– Nonsurgical treatment:
• Behavior modifications
• Nasal Continuous Positive Airway Pressure (CPAP)*
• AutoSet CPAP (APAP) devices – increased compliance*
– Surgical treatment:
• Uvulopalatopharyngoplasty (UPPP)
• Laser-assisted uvulopalatoplasty (LAUP)
• Future:
– Adaptive Servo Ventilation
* Discussion focused on CPAP/APAP – Standard of Care
34 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Behavioral Modifications
Methods:
•
Weight loss
•
Avoidance of alcohol, sedatives, antihistamines, smoking
•
Sleeping on side vs. back
Pros:
•
Lower risk (vs. surgical/invasive methods)
•
Easier to implement and lower cost
•
Even a moderate weight loss of 10% corresponds to ~30% decrease in AHI
Cons:
•
Requires active patient participation
•
Patient compliance low
35 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Positive Airway Pressure
Methods:
–
–
–
–
Pneumatic stent to keep upper airway open
Continuous positive airway pressure (CPAP): one pressure set
Bi-level (VPAP/BiPAP): two pressures set (inhalation/exhalation)
Auto-CPAP (APAP/AutoSet): device adjusts pressure automatically
Pros:
– Non-invasive therapy
– Demonstrated to improve AHI, SA symptoms, hypertension, heart
failure status, and other CVD outcomes with effective use
– Effective in 80-90% of patients (when used appropriately)
Cons:
– Patient compliance is an issue
• Intensive HME support and customization improves compliance
• New mask / device technologies improve compliance / efficacy
36 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Patient Using Small, Effective Mask
37 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Autotitration CPAP
(APAP or AutoSet)
• AutoSet devices adjust positive airway pressure on a
breath-by-breath basis to suit patient needs as they
vary throughout the night.
• Acts like a “pacemaker” for sleep apnea with a
“preemptive ICD” – algorithm senses and adjusts
pressure support as needed to prevent apnea,
hypopneas, snore, and flow limitation
• Record patient specific data regarding compliance,
device/mask function, and efficacy.
38 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
AutoSet for OSA How it works
• AutoSet Sensors (algorithm triggers)
–
–
–
–
–
apneas,
hypopneas,
flow limitation (shape-change of flow-time curve),
snore (flow vibration),
compensation for mask leak
• Ramp pressure to maintain open airway – algorithm
approach – preemptive to apnea
• Able to compensate for both intra-night as well as
night-to-night variability
39 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
AutoSet for OSA –
Advantages for Patients
• AutoSet more comfortable than basic CPAP
• Patients report more restful sleep, better quality of
sleep, less discomfort from pressure
• Immediate benefits once therapy begins: patients
report less trouble getting to sleep
• Varies therapy dose automatically
• Electronic feedback to home medical equipment
company – no need for patient diary
• Improves compliance and efficacy
40 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
AutoSet for OSA
Advantages for Clinicians - 1
• Easier to initiate and titrate – out of the box
• AutoSet has improved patient comfort,
compliance, and quality-of-life outcomes (Massie et
al. Am J Crit Care Med v167 pp 20-23 2003)
• Equivalent apnea prevention as CPAP (Lloberes et
al. Am J Crit Care Med v154; pp1755-1758 1996)
• Especially useful in patients requiring higher
treatment pressures (Randerath et al. Med Sci Monit 2003)
41 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
AutoSet for OSA
Advantages for Clinicians - 2
• Lower mean pressure overnight
– AutoSet mean pressure 37% lower than traditional CPAP
– Reduces pressure related side-effects: only uses high pressure
when clinically necessary
– No negative effects on sleep architecture or fragmentation
• Automatically adjusts as patient’s needs change both
inter-night and intra-night
– e.g., weight gain or loss, improving or decompensated
CHF, REM-related apnea, sleeping position, alcohol, etc.
• AutoSet tracks compliance and efficacy
– Compliance – hours of use at pressure
– Efficacy – Mask Leak, and treatment AHI
42 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Patient Using APAP and Mask
43 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Conclusions on Therapy
• Sleep Apnea is common in patients with
cardiovascular disease
• CPAP treatment of sleep apnea is safe and
effective
• AutoSet devices (APAP) improve patient
comfort, compliance, and quality-of-life
outcomes
44 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Therapeutic
Outcomes
New Therapies for
OSA and CSA
Waking people up to sleep
Obstructive Sleep Apnea - OSA
(effort to breathe; no flow)
EEG
EOG/L
EOG/R
EMG
EKG
LAT/RAT
SNORING
FLOW
NEED REFERENCES FOR THIS SLIDE
Effort/Thorax
Effort/Abdn
SaO2
46 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
AutoSet Spirit (APAP) for
Obstructive Sleep Apnea (OSA)
• Pilot Data of AutoSet on OSA in CHF patients
• After 3 months of AutoSet therapy (n=10)
–
–
–
–
–
Apnea-Hypopnea Index – reduced by 90%
BNP – reduced by 45%
6 minute walk – increased by 20%
LVEF – increased by 5%
Cardiac Output – no significant change
Source: Maisel et al., UCSD, VA Hospital, 2004
47 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Obstructive Sleep Apnea and
Congestive Heart Failure
Case Study: 69 year-old, male
450
AHI = 26 events per hour
Nadir O2 was 81%
400
AutoSet download
Mask Leak noted
350
BNP
(pg/mL)
300
250
200
150
100
AutoSet download
Compliance > 4 hrs/night
AHI<5 events/hour
50
0
Baseline
1.5 Months
Leak eliminated
C>4h/n AHI<5
3 Months
8 Months
Source: Maisel et al., UCSD, VA Hospital, 2004
48 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Obstructive Sleep Apnea and
Congestive Heart Failure
Case Study: 69 year-old, male
6 min. walk (feet)
2000
1500
Leak eliminated
C>4h/n AHI<5
AHI = 26 per hour
Nadir O2 = 81%
1000
Up 35%
AutoSet download
Mask Leak noted
500
0
Baseline
3 Months
8 Months
Source: Maisel et al., UCSD, VA Hospital, 2004
49 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Conclusions
• AutoSet devices are easier to initiate, adjust to changes
over time, and provide feedback
• AutoSet devices may increase the number of patients
successfully treated for Sleep Apnea leading to
improved cardiovascular outcomes
• Summary of key cardiovascular outcomes improved
with positive airway pressure:
–
–
–
–
Blood Pressure
Ejection Fraction
Quality of Life
Survival Rate
50 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Central Sleep Apnea - CSA
(no effort to breathe; no flow)
EEG
EOG/L
EOG/R
EMG
EKG
LAT/RAT
FLOW
Effort/Thorax
Effort/Abdn
SaO2
51 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Adaptive Servo Ventilation for
Central Sleep Apnea (CSA)
• Pressure Support Adaptive Servo Ventilator
• Design Goals:
–
–
–
–
Direct suppression of CSA/CSR
More comfortable than traditional CPAP
Easier to introduce than CPAP & bi-level
Similar hemodynamic/cardiovascular benefits
• Called AutoSet CS*
– Central Sleep Apnea
– Cheyne-Stokes Respiration
52 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
Adaptive Servo Ventilation for
Central Sleep Apnea (CSA)
Mechanism of Action:
• Supplements ventilation during apneic and hypopneic
phases of breathing cycle
• Reduces support during hypercapneic phase to avoid
hyperventilation
• Target overall minute ventilation of 90% of the
ventilation of the past 300 seconds
53 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Adaptive Servo Ventilation for
Central Sleep Apnea (CSA)
• Patients with central sleep apnea treated with
oxygen, CPAP, bi-level, and Adaptive Servo
Ventilator (AutoSet CS*)
• N = 14 patients in Acute Setting
(Teschler H, et al., Am J Respir Crit Care Med 164: 614-19, 2001)
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
54 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
N=14
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
55 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
N=14
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
56 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Adaptive Servo Ventilation
Essen Long-term Study
• N=20 Patients in Chronic Setting (Home Study)
– N=10 patients
– N=10 placebo controls
• 6 months home therapy on AutoSet CS*
• Assess cardiac, respiratory, and QOL data
• N=12 completed and available
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
57 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Pilot Data: Essen Long-term Study
Adaptive Servo-Ventilation
Compliance 6.3 hr/night for 6 months
Key Outcomes:
• 27% improvement in VO2 max
• 35% improvement in 6 minute walk
• 38% improvement in MLHFQ
• 55% reduction in nocturia episodes
• 88% reduction in AHI
N=12
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
58 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
Adaptive Servo-Ventilation and
CSA/CSR
Airflow Measurement
Pressure from AutoSet CS
Blood Oxygen Level (SaO2%)
AutoSet CS* [on]
59 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004
* Informational purposes only
Currently in FDA trial
Not available for sale in the U.S.
AutoSet CS* [off]
Conclusions
• Adaptive Servo Ventilation suppresses CSA and CSR
• Adaptive Servo Ventilation is more effective than:
– Oxygen
– CPAP
– Bi-level
• Summary of key cardiovascular outcomes improved
with adaptive servo ventilation:
– VO2 max
– Six minute walk
– Minnesotta Living with Heart Failure Questionnaire
• AutoSet CS is currently in FDA trials
60 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004