APNÉIA OBSTRUTIVA DO SONO APNÉIA OBSTRUTIVA DO SONO e DOENÇA CARDIOVASCULAR e DOENÇA CARDIOVASCULAR Laboratório do Sono da Disciplina de Pneumologia Laboratório do Sono da Disciplina de Pneumologia InCor HC- FMUSP InCor HC- FMUSP Brailia 2008 Geraldo Lorenzi-Filho
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APNÉIA OBSTRUTIVA DO SONO APNÉIA OBSTRUTIVA DO SONO e DOENÇA CARDIOVASCULAR Laboratório do Sono da Disciplina de Pneumologia InCor HC- FMUSP Brailia 2008.
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APNÉIA OBSTRUTIVA DO SONOAPNÉIA OBSTRUTIVA DO SONOe DOENÇA CARDIOVASCULARe DOENÇA CARDIOVASCULARLaboratório do Sono da Disciplina de Pneumologia Laboratório do Sono da Disciplina de Pneumologia
InCor HC- FMUSPInCor HC- FMUSP
Brailia2008
Geraldo Lorenzi-Filho
Trudo FJ, Am J Respir Crit Care Med, 1998Trudo FJ, Am J Respir Crit Care Med, 1998
Prevalência de Distúrbios Respiratórios do Sono entre as Doenças Cardiovasculares
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
17
OSA »» Atherosclerosis
AtherosclerosisOSA
HYP
++ +++
OSA »» Atherosclerosis
AtherosclerosisOSA
HYP
++
Ambulatory BP monitoring x clinicAmbulatory BP monitoring x clinic
24 hs 24 hs
BP BP
monitoringmonitoring
Time (hs)
• OSA is associated with absence of nocturnal BP dipping
Suzuki M et all Sleep 1996, 19 (5): 32-7
24 hs 24 hs
BP BP
monitoringmonitoring
Time (hs)
• OSA is associated with absence of nocturnal BP dipping
Suzuki M et all Sleep 1996, 19 (5): 32-7
• Masked Hypertension in OSA 35% Normotensives130 OSA patients 30% Masked HYP 35% HYP
Baguet JP et all J Hypertens 2008, 26 (5): 885-92
Ambulatory BP monitoring x clinic
24 hs BP monitoring24 hs BP monitoring
Somers VK et al. J Clin Invest 1995;96:1897-904
30 min
1 min
Acute modulation of arterial vasomotor tone
• Impaired endothelial relaxation?
Jelic et all Sleep 25(8): 15-20, 2002
Mean arterial pressure
11 ± 6%
8 ± 2 %
Balfors & Franklin AJRCCM150: 1587-1591, 1994
Shear stress
OSA and LV hypertrophyOSA and LV hypertrophy
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 m
ass
inde
xLV
mas
s in
dex **
****
*P<0,05*P<0,05
Left ventricular hypertrophyLeft ventricular hypertrophy
0
20
40
60
Control OSA HYP OSA +HYP
**
% L
V hy
petr
ophy
% L
V hy
petr
ophy
**
*** ** *
*P<0,05 * * P<0,0001*P<0,05 * * P<0,0001Drager LF et al. Chest 2007;131:1379-1386Drager LF et al. Chest 2007;131:1379-1386
Arterial StiffnessArterial Stiffness
88,5
99,510
10,511
11,512
12,513
Control OSA HTN OSA + HTN
PWV
(m/s
)PW
V (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;131:1379-1386
LV mass index vs PWVLV mass index vs PWV
PWV (m/s)PWV (m/s)77 99 1111 1313 1515 1717
180180
150150
120120
9090
6060
3030
R=0.72; P<0.0001R=0.72; P<0.0001
LV m
ass
inde
xLV
mas
s in
dex
Drager LF et al. Chest 2007;131:1379-1386Drager LF et al. Chest 2007;131:1379-1386
Heart RemodelingHeart Remodeling
After LoadAfter Load
LV remodelingLV remodeling
Drager LF et al. Chest 2007;131:1379-1386Drager LF et al. Chest 2007;131:1379-1386
Arterial Arterial stiffnessstiffness
HYP
&
OSA
OSA »» Atherosclerosis
AtherosclerosisOSA
HYP
++ +++
LIP+ +++
Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7
Intermittent Hypoxia and AtherosclerosisIntermittent Hypoxia and AtherosclerosisAnimal ModelAnimal Model
40 male mice
12 weeks
Regular chow diet
Intermittent air
High cholesterol dietIntermittent air
Regular chow diet
Intermittent hypoxia
High cholesterol dietIntermittent hypoxia
IH or Colesterol Diet » NO Aterosclerosis
Control IH
Cholesterol Diet
Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7
IH + Colesterol Diet » » Aterosclerosis
Control
Cholesterol + IH
IH
Cholesterol Diet
Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7
OSA »» Atherosclerosis
AtherosclerosisOSA
HYP
++ +++
LIP
Inflammation
+++
+++
+
+
SAOS e eventos cardiovascularesSeguimento de 10 anos: Eventos fatais
Marin JM et al. Lancet. 2005Marin JM et al. Lancet. 2005
Controles
RoncadoresRoncadores
SAOS leveSAOS leve
SAOS graveSAOS grave
SAOS - CPAPSAOS - CPAP
Inci
dênc
ia a
cum
ulad
a de
eve
ntos
fata
is (%
)In
cidê
ncia
acu
mul
ada
de e
vent
os fa
tais
(%)
SAOS e arritimia: Fibrilação Atrial
Kanagala R et al. Circulation 2003Kanagala R et al. Circulation 2003
Rec
orrê
ncia
de
FA
Rec
orrê
ncia
de
FA
após
12
mes
esap
ós 1
2 m
eses
0102030405060708090
100
Controles SAOS tratado SAOS nãotratado
P=0.46P=0.46
P=0.009P=0.009
P=0.013P=0.013
SAOS e Morte SúbitaSAOS e Morte Súbita
NEJM, 2005NEJM, 2005
Early Signs of Atherosclerosis in Patients with Obstructive Sleep Apnea
Luciano F Drager, Luiz A Bortolotto, Maria Cecília Lorenzi, Adelaide C Figueiredo, Eduardo M Krieger and Geraldo
Lorenzi-Filho
Sleep Laboratory, Pulmonary Division, Heart Institute (InCor), University of São Paulo Medical School, Brazil
Methods
• 15 severe OSA patients• 15 mild-to-moderate OSA patients • 12 age and sex-matched healthy volunteers • All participants were free of hypertension, diabetes,
smoking and were not on any medications. OSA patients were naive to treatment.