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 Prevalência de Distúrbios Respiratórios do Sono entre as Doenças Cardiovasculares 35% 70% Hipertensão 50% Insuficiência cardíaca Hipertensão Refratária 30% Doença Coronariana 50% Fibrilação Atrial Leung. AJRCCM 2003 Factors associated with OSA • • • • • Male Age Hypertension Dislipidemia Diabetes OSA Risk factors for Atherosclerosis • • • • • • Male Age Hypertension Dislipidemia Diabetes Smoking OSA Atherosclerosis Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea Normotensive N = 76 Hypertensive N = 76 Age, yrs 4713 6011 <0.001 BMI, kg.m2 315 363 <0.001 9% 34% 0.004 Glucose, mg.dl 9811 11337 0.01 History of Hyp 54% 79% 0.01 Diabetes Drager LF et al J Hum Hypertens 2006 Jul;20(7):523-8 p OSA »»atherosclerosis ? • • • • • • Male Age Hypertension Dislipidemia Diabetes Smoking Causal Link ? OSA Atherosclerosis How can OSA affect the CV system ronco S2 SaO2 Obstructive event SaO2 Arousal SaO2 78% 94% Snore Carotid Arteries 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 Eventos/hora > 15 5.0 - 14.9 0.1 - 4.9 0 0 0,5 1 1,5 2 2,5 3 3,5 Odds Peppard PE et al. NEJM 2000;342:1378-84. TRATAMENTO DA APNÉIA OBSTRUTIVA DO SONO CPAP “continuous positive airway pressure” Sullivan, 1981 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 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 OSA and LV* hypertrophy 130 * LV mass index 120 * 110 * 100 90 80 70 60 *P<0,05 Control OSA HTN OSA + HTN Drager LF et al. Chest 2007;131:1379-1386 Left ventricular hypertrophy ** % LV hypetrophy 60 * 40 * * 20 0 Control *P<0,05 * * P<0,0001 OSA HYP OSA + HYP Drager LF et al. Chest 2007;131:1379-1386 Arterial Stiffness PWV (m/s) <0.001 13 12,5 12 11,5 11 10,5 10 9,5 9 8,5 8 <0.007 <0.001 <0.007 <0.001 NS 12,1 10,7 10,1 8,7 Control OSA HTN OSA + HTN Drager LF et al. Chest 2007;131:1379-1386 LV mass index vs PWV R=0.72; P<0.0001 60 90 150 120 LV mass index 180 30 7 9 13 11 15 17 PWV (m/s) Drager LF et al. Chest 2007;131:1379-1386 Heart Remodeling HYP LV remodeling & OSA Arterial stiffness After Load Drager LF et al. Chest 2007;131:1379-1386 OSA »» Atherosclerosis HYP +++ ++ + OSA LIP +++ Atherosclerosis Intermittent Hypoxia and Atherosclerosis Animal Model 40 male mice 12 weeks Regular chow diet Regular chow diet Intermittent air Intermittent hypoxia High cholesterol diet Intermittent air High cholesterol diet Intermittent hypoxia 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 Diet Cholesterol + IH Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7 OSA »» Atherosclerosis HYP +++ ++ + LIP OSA +++ Atherosclerosis + Inflammation +++ SAOS e eventos cardiovasculares Incidência acumulada de eventos fatais (%) Seguimento de 10 anos: Eventos fatais Controles Roncadores SAOS leve SAOS grave SAOS - CPAP Marin JM et al. Lancet. 2005 SAOS e arritimia: Fibrilação Atrial Recorrência de FA após 12 meses P=0.009 100 90 80 70 60 50 40 30 20 10 0 P=0.46 P=0.013 Controles SAOS tratado SAOS não tratado 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 Control (n=12) Mild-moderate OSA (n=15) Severe OSA (n=15) P Age (years) 42 2 43 1 44 1 0.67 Males (%) 93 93 84 0.64 Body mass index (Kg/m2) 28.9 0.7 28.4 0.6 29.3 0.8 0.66 Caucasians (%) 83 67 80 0.35 SBP (mm Hg) 115.4 3.5 114.2 2.5 117.4 3.0 0.74 Heart rate (bpm) 75 2 75 2 76 2 0.87 Fasting glucose (mg/dL) 96 2 95 3 98 1 0.74 Cholesterol (mg/dL) 226 14 226 6 236 8 0.67 AHI (events/hour) 3.1 0.3 16.2 1.7 55.7 5.9 <0.0001 Minimal oxygen saturation 90 1 81 1 73 1 <0.0001 (SatO2min) Pulse wave velocity CCA A D CF CR A B RA T FA B Eco-tracking ANT POST PWV 11 PWV (m/s) * 10 * p<0.0001 9 8 Control Mild-to-Moderate OSA Severe OSA IMT † 800 IMT (m) 750 † p<0.0001 700 650 600 550 500 Control Mild-to-Moderate OSA Severe OSA Carotid Diameter Carotid Diameter (m) 8000 § ‡ 7500 7000 6500 6000 Control Mild-to-Moderate OSA Severe OSA PWV P<0,001 P<0,001 13 13 12 12 PWV (m/s) PWV (m/s) NS 11 10 9 11 10 9 8 8 7 7 Basal 4 months Grupo Controle Basal 4 months CPAP Drager LF et al. Am J Respir Crit Care Med. 2007 Espessura íntima-média da carótida P=0,02 P=0,04 1200 1200 1100 1100 1000 1000 900 900 (µm) (µm) NS 800 800 700 700 600 600 500 500 400 400 Basal 4 meses Grupo Controle Basal 4 meses CPAP Drager LF et al. Am J Respir Crit Care Med. 2007 “Eu dormia, mas meu coração estava acordado” LABORATÓRIO DO SONO INSTITUTO DO CORAÇÃO Cântico de Salomão, Cap 5, V 2.
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