APNÉIA OBSTRUTIVA DO SONO e DOENÇA CARDIOVASCULAR

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

2. Trudo FJ, Am J Respir Crit Care Med, 1998

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

4. Factors associated with OSA • Male •  Age • Hypertension • Dislipidemia • Diabetes OSA

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

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

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

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

9. Snore  Carotid Arteries SNORE Carotid Arteries Vibration OBSTRUTIVE APNEA SaO2 78% 94%

10. CPAP  OSA CPAP--------------------------

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

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

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

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

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

17. OSA Cause of Hypertension 17

18. OSA »» Atherosclerosis HYP +++ ++ OSA Atherosclerosis

19. OSA »» Atherosclerosis HYP ++ OSA Atherosclerosis

20. 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)

21. 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

22. 24 hs BP monitoring 30 min 1 min Somers VK et al. J Clin Invest 1995;96:1897-904

23. 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

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

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

26. Arterial Stiffness <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

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

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

29. OSA »» Atherosclerosis HYP +++ ++ LIP +++ + OSA Atherosclerosis

30. 40 male mice 12 weeks Intermittent Hypoxia and AtherosclerosisAnimal Model Regular chow diet Intermittent hypoxia Regular chow diet Intermittent air Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7 High cholesterol diet Intermittent hypoxia High cholesterol diet Intermittent air

31. IH or  Colesterol Diet » NO Aterosclerosis Control IH  Cholesterol Diet Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7

32. IH +  Colesterol Diet » » Aterosclerosis Control IH  Cholesterol + IH  Cholesterol Diet Savranski et al. Am J Resp Crit Care Med. 2007;175:1290-7

33. OSA »» Atherosclerosis HYP +++ ++ + +++ LIP OSA Atherosclerosis + +++ Inflammation

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

36. 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

37. SAOS e Morte Súbita NEJM, 2005

38. 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

39. 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.

40. Baseline Characteristics

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

42. Eco-tracking ANT POST

43. PWV * p<0.0001

44. IMT † p<0.0001

45. Carotid Diameter

46. 13 13 12 12 11 11 10 10 9 9 8 8 7 7 P<0,001 NS P<0,001 PWV 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

47. 1200 1100 1000 900 800 700 600 500 400 P=0,02 NS P=0,04 1200 Espessura íntima-média da carótida 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

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