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CONSEQUENCES OF SLEEP APNEA SYNDROME Yüksel Peker MD, PhD, Associate Professor

CONSEQUENCES OF SLEEP APNEA SYNDROME Yüksel Peker MD, PhD, Associate Professor Sleep Medicine Unit, Skaraborg Hospital, Skövde & University of Gothenburg, Sweden. Wife stabbed snoring husband. rescued by thoracic surgeons. OSA (Asymptomatic OSA; “Non-sleepy sleep apnoeics”)

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CONSEQUENCES OF SLEEP APNEA SYNDROME Yüksel Peker MD, PhD, Associate Professor

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  1. CONSEQUENCES OF SLEEP APNEA SYNDROME Yüksel Peker MD, PhD, Associate Professor Sleep Medicine Unit, Skaraborg Hospital, Skövde & University of Gothenburg, Sweden

  2. Wife stabbed snoring husband rescued by thoracic surgeons

  3. OSA (Asymptomatic OSA; “Non-sleepy sleep apnoeics”) • OSAS (Symptomatic OSA; “Sleepy sleep-apnoeics”)

  4. OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS) OSA + Daytime sleepinessTreatment indication

  5. Prevalence (30-60 yrs) Men Women OSA 24 % 9 % OSAS 4 % 2 % The majority of the patients with OSA do not report daytime sleepiness

  6. OSA increases by age Eight-year follow-up AHI versus baseline AHI in the Wisconsin Sleep Cohort Study (n= 282) Young Tet al, AJRCCM 2002

  7. OSAS decreases after age of 64? Bixleret al, AJRCCM 1998 % Do they • become asymptomatic? • die?

  8. OSA • Immediate changes • Long-term effects

  9. OSA • Immediate changes • Long-term effects

  10. Grote L. et al., J. Cardiovasc. Pharmacol. 1994

  11. Cardiovascular mechanisms (I) Repeated nocturnal hypoxemia Coccogna G et al, 1972; Podszus T et al, 1986 Sympathetic nervous activity Fletcher EC et al, 1987; Hedner J et al, 1988; Narkiewicz K & Somers VK 2003 Vascular endothelial dysfunction Carlson J et al, 1996; Remsburg S et al, 1999; Kraiczi H et al, 2000

  12. Cardiovascular mechanisms (II) Enhanced release of superoxide from polymorphonuclear neutrophils in OSA. Impact of CPAP. Schulz Ret al, AJRCCM 2000 Plasma vascular endothelial growth factor in OSAS: Effects of CPAP. Lavie L et al, AJRCCM 2002 Elevated levels of C-reactive protein and interleukin-6 in patients with OSAS are decreased by CPAP. Yokoe Tet al, Circulation 2003

  13. Pulse-oximetry Oxygen saturation % Heart rate 50 % Time

  14. OSA & CVD • Immediate changes • Long-term effects

  15. Hypnogram Lights Out MT Normal Wake REM S1 S2 S3 S4 00:00 02:00 04:00 06:00 08:00 OSA Lights Out MT Wake REM S1 S2 S3 S4 00:00 01:00 02:00 03:00 04:00 05:00 06:00 07:00

  16. Long-term complications • Cognitive dysfunction • Cardiovascular dysfunction

  17. AHI 30 AHI 30 AHI 30 AHI 30 AHI 30 AHI 30

  18. Long-term complications • Cognitive dysfunction • Cardiovascular dysfunction

  19. Clinical and epidemiological aspects Obstructive sleep apnea is associated with Hypertension Coronary heart disease Cardiac arrhythmias Heart failure Stroke Diabetes and Insulin Resistance Mortality

  20. CVD OSA OSAS

  21. CVD OSA Obesity

  22. OSA & CAD

  23. Prevalence of CAD in Sleep Clinic Cohorts CAD in 25% of unselected patients with OSA More common in severe OSA Maekawa M et al, Psychiatry Clin Neurosci 1998

  24. First author publ yr n AHI10 controls De Olazabal 1982 Andreas 1996 Mooe 1996 Mooe 1996 Koehler 1996 Peker 1999 Moruzzi 1999 Sanner 2001 Mehra 2006 Takama 2007 Yumino 2007 17 50 142 102 74 62 22 49 104 65 89 76 % 50 % 37 % 30 % 35 % 31 % 9 % 27 % 66 % 45 % 57 % yes yes yes Total 776 42% Prevalence of OSA in CAD clinic cohorts

  25. Explanatory variables associated with CAD (multivariate analysis) _______________________________________________________________________________________Odds Ratio 95 % CI p values_______________________________________________________________________________________Current smoking 9.8 2.6-36.5 0.001Diabetes mellitus 4.2 1.1-17.1 0.045Obstructive sleep apnea 3.1 1.2-8.3 0.025_______________________________________________________________________________________ Peker et al, ERJ 1999

  26. Prognosis of CAD with concomitant OSA is WORSE than the prognosis of CAD patients without OSA Peker et al, AJRCCM 2000 Mooe et al, AJRCCM 2001 Yumino et al, Am J Cardiol 2007

  27. Prognosis of CAD after PCI in patients with concomitant OSA 89 consecutive patients with acute coronary syndrome who were successfully treated with PCI OSA in 51 patients (57%); follow-up period 6 months Major cardiac event (cardiac death, reinfarction, revascularization) 23.5 % in OSA, 5.3 % in non-OSA (p=0.020) Odds ratio for OSA 11.6 (95% CI 2.2-62-2) Yumino et al, Am J Cardiol 2007

  28. Peker et al, AJRCCM 2000

  29. Hazard function of death estimated by use of Poisson model Peker et al, AJRCCM 2000

  30. Prognosis of CAD with concomitant OSA is NOT WORSE than the prognosis for CAD patients without OSA 50 CAD patients (25 OSA, 25 non-OSA) Follow-up period 10 years Cardiac death in 4 versus 5 patients (ns) Hagenah et al, Respir Med 2006

  31. Weak association between OSA & CAD in a general population Sleep Heart Health Study Cross-sectional analysis (n=6,132) Adjusted OR for OSA 1.27 (95% CI 0.99-1.62) (AHI>11 versus AHI<1.4) Shahar E et al, AJRCCM 2001

  32. CAUSALITY Incident CAD in OSA Impact of treatment of the OSA on CAD

  33. All normotensive at baseline AJRCCM 2002

  34. CAD incidence in a sleep-clinic cohort at a 7-yr follow-up % Peker et al, ERJ 2006

  35. Probability of CAD incidence estimated by Poisson modelStart age 49 yrs, Systolic BP 133 mmHg and Sat. min 86% Peker et al, ERJ 2006

  36. OSA & Stroke

  37. First author publ yr n AHI10 controls Bassetti 1996 Dyken 1996 Bassetti 1999 Wessendorf 2000 Parra 2000 Iranzo 2002 Hui 2002 Turkington 2002 Kaneko 2003 Bassetti 2006 59 24 128 147 161 50 51 120 61 152 69 % 71 % 63 % 44 % 71 % 62 % 67 % 61 % 72 % 58 % yes yes Total 953 67% Prevalence of sleep apnea in acute stroke/TIA

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