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Conseqüências Cardiovasculares da AOS
Geraldo Lorenzi-Filho
Professor Livre Docente
Lab do Sono, Disciplina de Pneumologia
InCor, FM USP
Conflito de interess
• Laboratório do sono do InCor– Grants e colaboração– Philips-Respironics– Resmed– Fisher-Paykel– Equipamentos
– FAPESP, Fundação Zerbini, CnPq, Finep
Prevalência de Distúrbios Respiratórios do Sono entre as Doenças Cardiovasculares
HipertensãoHipertensão
35%35%
Hipertensão Hipertensão RefratáriaRefratária
70%70%
Doença Doença CoronarianaCoronariana
Fibrilação Fibrilação AtrialAtrial
Insuficiência Insuficiência cardíacacardíaca
50%50%
50%50%
30%30%
Leung. AJRCCM 2003
SaO2SaO2
94%94%78%78%
SNORESNORE
OBSTRUTIVEOBSTRUTIVE
APNEAAPNEA
Polissonografia
De que forma a AOS pode afetar o SCV?
SaO2SaO2
94%94%
SNORESNORE
OBSTRUTIVEOBSTRUTIVE
APNEAAPNEA
SaOSaO22SaOSaO22SaOSaO22
SaOSaO22
COCO22COCO22COCO22
COCO22
De que forma a AOS pode afetar o SCV?
SaO2SaO2
94%94%78%78%
AROUSALAROUSAL
SNORESNORE
OBSTRUTIVEOBSTRUTIVE
APNEAAPNEA
SaOSaO22SaOSaO22SaOSaO22
SaOSaO22
COCO22COCO22COCO22
COCO22
De que forma a AOS pode afetar o SCV?
SaO2SaO2
94%94%78%78%
AROUSALAROUSAL
SNORESNORE
OBSTRUTIVEOBSTRUTIVE
APNEAAPNEA
SaOSaO22SaOSaO22SaOSaO22
SaOSaO22
------------
--------
----
COCO22COCO22COCO22
COCO22
CPAP--------------------------
CPAP OSA
APNEIA OBSTRUTIVA DO SONO
Conceitos
• Hipertensão Arterial Sistêmica
• Arritimia Cardíaca
• Mortalidade
• Aterosclerose
CPAP and BPCPAP and BP
Before Before AfterAfter
Pepperell JC et al. Lancet. 2002;359:204-10.Pepperell JC et al. Lancet. 2002;359:204-10.
OSA OSA
Cause of Cause of HypertensionHypertension
11
APNEIA OBSTRUTIVA DO SONO
Conceitos
Hipertensão Arterial Sistêmica
• Arritimia Cardíaca
• Mortalidade
• Aterosclerose
SAOS e arritimia: Fibrilação Atrial
Kanagala R et al. Circulation 2003Kanagala R et al. Circulation 2003
Rec
orrê
ncia
de
Rec
orrê
ncia
de
FA
apó
s 12
F
A a
pós
12
mes
esm
eses
0102030405060708090
100
Controles SAOS tratado SAOS nãotratado
P=0.46P=0.46
P=0.009P=0.009
P=0.013P=0.013
APNEIA OBSTRUTIVA DO SONO
Conceitos
Hipertensão Arterial Sistêmica
Arritimia Cardíaca
• Mortalidade
• Aterosclerose
SAOS e Morte SúbitaSAOS e Morte Súbita
Gami et al Gami et al N Engl J Med. 2005;352(12):1206-14N Engl J Med. 2005;352(12):1206-14..
OSA and fatal cardiovascular eventsFollow up 10 years
Marin JM et al Lancet 365: 1046-1053, 2005Marin JM et al Lancet 365: 1046-1053, 2005
264 377
403 235
372
1,651
OSA and fatal cardiovascular events
Marin JM et al Lancet 365: 1046-1053, 2005Marin JM et al Lancet 365: 1046-1053, 2005
Number HR (IC) Cohort Publication
1,651Heathy subjectsSevere OSA(n= 235)
2.87 (1.17 – 7.51)
Spain Follow up
10 y
J Marin Lancet2005
OSA and fatal cardiovascular events
Number HR (IC) Cohort Publication
1,651Heathy subjectsSevere OSA(n= 235)
2.87 (1.17 – 7.51)
Spain J Marin Lancet2005
Wisconsin Cohort: Population Based Study 1,522 subjectsWisconsin Cohort: Population Based Study 1,522 subjects
Young T et al, SLEEP 31(8): 1071-1078, 2008Young T et al, SLEEP 31(8): 1071-1078, 2008
OSA and fatal cardiovascular events
Number HR (IC) Cohort Publication
1,651Heathy subjectsSevere OSA(n= 235)
2.87 (1.17 – 7.51)
Spain J Marin Lancet2005
1,522No OSASevere OSA(n = 63)
3.8 (1.6 – 9.0)
Wisconsin
Follow up18 y
Young TSLEEP2008
OSA and fatal cardiovascular events
Number HR (IC) Cohort Publication
1,651Heathy subjectsSevere OSA(n= 235)
2.87 (1.17 – 7.51)
Spain J Marin Lancet2005
1,522No OSASevere OSA(n = 63)
3.8 (1.6 – 9.0)
Wisconsin
Young TSLEEP2008
Sleep Heart Health Study 6,441 subjects from different cohorts across USA Sleep Heart Health Study 6,441 subjects from different cohorts across USA
Punjab N et al PLOS: 6 (8) e 100132, 2009Punjab N et al PLOS: 6 (8) e 100132, 2009
OSA and fatal cardiovascular events
Number HR (IC) Cohort Publication
1,651Heathy subjectsSevere OSA(n= 235)
2.87 (1.17 – 7.51)
SpainFollow up
10 y
J Marin Lancet2005
1,522No OSASevere OSA(n = 63)
3.8 (1.6 – 9.0)
WisconsinFollow up
18 y
Young TSLEEP2008
6,441No OSASevere OSA(n= 341)
1. 5 (1.1 – 1.9)
SHHSFollow up
8.2 y
PunjabPLOS2009
APNEIA OBSTRUTIVA DO SONO
Conceitos
Hipertensão Arterial Sistêmica
Arritimia Cardíaca
Mortalidade – Estudo SAVE
• Aterosclerose
Arterial Stiffness Arterial Stiffness Pulse wave velocity (PWV)Pulse wave velocity (PWV)
A D B
A
B
T
CCACCA
CRCRCFCF
RARA
FAFA
Echo-trackingEcho-tracking
Intima media thickness (IMT) Intima media thickness (IMT)
Carotid diameterCarotid diameterANTANT POSPOSTT
OSA »»atherosclerosis ?
OSAOSA HTNHTN
• Male Age• Hypertension• Dislipidemia• Diabetes
No co-morbidities
~ 50% of OSA - HTN~30% of HTN - OSA
Arterial StiffnessArterial Stiffness
8
8,5
9
9,5
10
10,5
11
11,5
12
12,513
Control OSA HTN OSA + HTN
PW
V (
m/s
)P
WV
(m
/s)
8,78,7
10,710,710,110,1
12,112,1
<0.001<0.001
<0.001<0.001
<0.007<0.007
NSNS<0.001<0.001
<0.007<0.007
Drager LF et al. Chest 2007;131:1379-1386Drager LF et al. Chest 2007;131:1379-1386n = 15 15 15 15
OSA and LV OSA and LV hypertrophyhypertrophy
Drager LF et al. Chest 2007;131:1379-1386Drager LF et al. Chest 2007;131:1379-1386
60
70
80
90
100
110
120
130
Control OSA HTN OSA+HTN
**
LV
ma
ss in
de
xL
V m
ass
ind
ex **
**** *P<0,05*P<0,05
n = 15 15 15 15
Carotid Intima Media Thickness Carotid Intima Media Thickness ((m)m)
Drager LF et al. Hypertension 53: 64-69 2009Drager LF et al. Hypertension 53: 64-69 2009n 22 25 20 27
Carotid DiameterCarotid Diameter ( (m)m)
Drager LF et al. Hypertension 53: 64-69, 2009Drager LF et al. Hypertension 53: 64-69, 2009
n 22 25 20 27
Carotid Distensibility (KpaCarotid Distensibility (Kpa-1-1 10 10-3-3))
Drager LF et al. Hypertension 53: 64-69, 2009Drager LF et al. Hypertension 53: 64-69, 2009n 22 25 20 27
The impact of continuous positive The impact of continuous positive
airway pressure (CPAP) on airway pressure (CPAP) on
validated markers of validated markers of
atherosclerosis. atherosclerosis.
Drager LF et al. Drager LF et al. Am J Respir Crit Care Med.Am J Respir Crit Care Med. 2007;176:706-12. 2007;176:706-12.
MethodsMethods
No treatment (NT)No treatment (NT)
(N=12)(N=12)
24-h blood pressure monitoring24-h blood pressure monitoringSerum catecholamineSerum catecholamine
C-reactive protein C-reactive protein
VASCULAR PARAMETERSVASCULAR PARAMETERS
24 OSA patients AHI>3024 OSA patients AHI>30
CPAPCPAP
(N=12)(N=12)
4 months4 months
RandomizationRandomization
Baseline Baseline
Pulse Wave Velocity
Arterial Stiffness
BaselineBaseline 4 months4 months
OSA-NTOSA-NT OSA-CPAPOSA-CPAP
NSNS
77
88
99
1010
1111
1212
1313
PW
V (
m/s
)P
WV
(m
/s)
BaselineBaseline 4 months4 months
P=0.002P=0.002
PW
V (
m/s
)P
WV
(m
/s)
77
88
99
1010
1111
1212
1313
P<0.001P<0.001
Drager LF et al. Drager LF et al. Am J Respir Crit Care Med.Am J Respir Crit Care Med. 2007;176:706-12. 2007;176:706-12.
Intima-media thickness
BaselineBaseline 4 months4 months
OSA-NTOSA-NT OSA-CPAPOSA-CPAP
NSNS
BaselineBaseline 4 months4 months
P=0.04P=0.04
P=0.02P=0.02
IMT (
IMT (
µm
)µ
m)
400400
500500
600600
700700
800800
900900
10001000
11001100
12001200
400400
500500
IMT (
IMT (
µm
)µ
m)
600600
700700
800800
900900
10001000
11001100
12001200
Drager LF et al. Drager LF et al. Am J Respir Crit Care Med.Am J Respir Crit Care Med. 2007;176:706-12. 2007;176:706-12.
Carotid Diameter
BaselineBaseline 4 months4 months
OSA-NTOSA-NT OSA-CPAPOSA-CPAP
NSNS
BaselineBaseline 4 months4 months
NSNS
NSNS
55005500
Caro
tid
dia
mete
r (
Caro
tid
dia
mete
r ( µ
m)
µm
)
60006000
65006500
70007000
75007500
80008000
85008500
90009000
95009500
55005500
Caro
tid
dia
mete
r (
Caro
tid
dia
mete
r ( µ
m)
µm
)
60006000
65006500
70007000
75007500
80008000
85008500
90009000
95009500
Drager LF et al. Drager LF et al. Am J Respir Crit Care Med.Am J Respir Crit Care Med. 2007;176:706-12. 2007;176:706-12.
Conclusão
• AOS é pouco diagnosticada, e quando não tratada faz muito mal .....
• OBRIGADO!• [email protected]