APNÉIA OBSTRUTIVA DO SONO e DOENÇA CARDIOVASCULAR Laboratório do Sono da Disciplina de Pneumologia InCor HC- FMUSP Brailia 2008 Geraldo Lorenzi-Filho

Trudo FJ, Am J Respir Crit Care Med, 1998

Hipertensão Refratária Insuficiência cardíaca Prevalência de Distúrbios Respiratórios do Sono entre as Doenças Cardiovasculares 35% 70% Hipertensão Refratária Hipertensão 50% 30% Fibrilação Atrial 50% Insuficiência cardíaca Doença Coronariana Leung. AJRCCM 2003

Factors associated with OSA Male  Age Hypertension Dislipidemia Diabetes OSA

 Risk factors for Atherosclerosis Male  Age Hypertension Dislipidemia Diabetes Smoking Atherosclerosis OSA

Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea Drager LF et al J Hum Hypertens 2006 Jul;20(7):523-8

OSA »»atherosclerosis ? Male  Age Hypertension Dislipidemia Diabetes Smoking Causal Link ? Atherosclerosis OSA

How can OSA affect the CV system ronco S2 Arousal - Obstructive event SaO2 SaO2 78% 94%

Snore  Carotid Arteries Vibration OBSTRUTIVE APNEA SaO2 78% 94%

CPAP  OSA CPAP--------------------------

Esra Tasali et all PNAS 105 (3):1044-1049, 2008

Slow-wave sleep and the risk of type 2 diabetes Esra Tasali et all PNAS 105 (3):1044-1049, 2008

Wisconsin coort Peppard PE et al. NEJM 2000;342:1378-84.

CPAP TRATAMENTO DA APNÉIA OBSTRUTIVA DO SONO “continuous positive airway pressure” Sullivan, 1981

Before After Pepperell JC et al. Lancet. 2002;359:204-10. CPAP and BP Before After Pepperell JC et al. Lancet. 2002;359:204-10.

OSA Cause of Hypertension 17

OSA »» Atherosclerosis HYP +++ ++ OSA Atherosclerosis

OSA »» Atherosclerosis HYP ++ OSA Atherosclerosis

Ambulatory BP monitoring x clinic OSA is associated with absence of nocturnal BP dipping Suzuki M et all Sleep 1996, 19 (5): 32-7 24 hs BP monitoring Time (hs)

Ambulatory BP monitoring x clinic OSA is associated with absence of nocturnal BP dipping Suzuki M et all Sleep 1996, 19 (5): 32-7 24 hs BP monitoring Time (hs) Masked Hypertension in OSA 35% Normotensives 130 OSA patients 30% Masked HYP 35% HYP Baguet JP et all J Hypertens 2008, 26 (5): 885-92

24 hs BP monitoring 30 min 1 min Somers VK et al. J Clin Invest 1995;96:1897-904

Mean arterial pressure 11 ± 6% Mean arterial pressure  8 ± 2 % Balfors & Franklin AJRCCM150: 1587-1591, 1994 Acute modulation of arterial vasomotor tone Impaired endothelial relaxation? Jelic et all Sleep 25(8): 15-20, 2002 Shear stress

Drager LF et al. Chest 2007;131:1379-1386 OSA and LV hypertrophy * * * * LV mass index *P<0,05 Drager LF et al. Chest 2007;131:1379-1386

Left ventricular hypertrophy * * * * % LV hypetrophy * *P<0,05 * * P<0,0001 Drager LF et al. Chest 2007;131:1379-1386

Arterial Stiffness PWV (m/s) 12,1 10,7 10,1 8,7 <0.001 <0.007 <0.001 <0.007 <0.001 NS PWV (m/s) 12,1 10,7 10,1 8,7 Drager LF et al. Chest 2007;131:1379-1386

LV mass index vs PWV R=0.72; P<0.0001             180   150           120 LV mass index                   90                      60    30 7 9 11 13 15 17 PWV (m/s) Drager LF et al. Chest 2007;131:1379-1386

Heart Remodeling  Arterial stiffness  After Load HYP & LV remodeling OSA LV remodeling  Arterial stiffness  After Load Drager LF et al. Chest 2007;131:1379-1386

OSA »» Atherosclerosis HYP +++ ++ LIP +++ + OSA Atherosclerosis

Intermittent Hypoxia and Atherosclerosis Animal Model 40 male mice 12 weeks Regular chow diet Intermittent hypoxia Regular chow diet Intermittent air High cholesterol diet Intermittent hypoxia High cholesterol diet Intermittent air Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7

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 IH  Cholesterol + IH  Cholesterol Diet Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7

OSA »» Atherosclerosis HYP +++ ++ + +++ LIP OSA Atherosclerosis + +++ Inflammation

SAOS e eventos cardiovasculares Seguimento de 10 anos: Eventos fatais Controles Roncadores SAOS leve SAOS grave Incidência acumulada de eventos fatais (%) SAOS - CPAP Marin JM et al. Lancet. 2005

SAOS e arritimia: Fibrilação Atrial P=0.009 P=0.46 Recorrência de FA após 12 meses P=0.013 Kanagala R et al. Circulation 2003

SAOS e Morte Súbita NEJM, 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.

Baseline Characteristics

Pulse wave velocity CCA CR CF RA FA A D B  T

Eco-tracking ANT POST

PWV * p<0.0001

IMT † p<0.0001

Carotid Diameter

PWV P<0,001 Grupo Controle CPAP NS P<0,001 7 8 9 10 11 12 13 7 8 9 10 11 12 13 PWV (m/s) PWV (m/s) Basal 4 months Basal 4 months Grupo Controle CPAP Drager LF et al. Am J Respir Crit Care Med. 2007

Espessura íntima-média da carótida NS P=0,04 400 500 600 700 800 900 1000 1100 1200 1200 1100 1000 900 (µm) (µm) 800 700 600 500 400 Basal 4 meses Basal 4 meses Grupo Controle CPAP Drager LF et al. Am J Respir Crit Care Med. 2007

Cântico de Salomão, Cap 5, V 2. “Eu dormia, mas meu coração estava acordado” LABORATÓRIO DO SONO INSTITUTO DO CORAÇÃO Cântico de Salomão, Cap 5, V 2.