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SHOULD ALL OBSTRUCTIVE SLEEP APNEA PATIENTS BE TREATED? “YES!” Yüksel Peker MD*, PhD**

SHOULD ALL OBSTRUCTIVE SLEEP APNEA PATIENTS BE TREATED? “YES!” Yüksel Peker MD*, PhD** *Sleep Medicine Unit, Skaraborg Hospital, Skövde & **University of Gothenburg, Sweden. OSA (Asymptomatic OSA; “Non-sleepy sleep apnoeics”) OSAS (Symptomatic OSA; “Sleepy sleep-apnoeics”).

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SHOULD ALL OBSTRUCTIVE SLEEP APNEA PATIENTS BE TREATED? “YES!” Yüksel Peker MD*, PhD**

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  1. SHOULD ALL OBSTRUCTIVE SLEEP APNEA PATIENTS BE TREATED? “YES!” Yüksel Peker MD*, PhD** *Sleep Medicine Unit, Skaraborg Hospital, Skövde & **University of Gothenburg, Sweden

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

  3. Wisconsin Sleep Cohort (age 30-60 yrs) Men Women OSA 24 % 9 % OSAS 4 % 2 % Young et al, N Engl J Med 1993; 328: 1230-1235 Majority of the OSA patients do not report daytime sleepiness

  4. 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

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

  6. OSA • Immediate changes • Long-term effects

  7. complete AV block tachycardia apnea REM-sleep arousal modified from Becker et al, AJRCCM 1995

  8. 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

  9. 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

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

  11. 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

  12. Long-term complications • Cognitive dysfunction • Daytime sleepiness • Cardiovascular dysfunction

  13. DAYTIME SLEEPINESS

  14. “Sleepy” OSA patients should be treated! No doubt! Evidence based data on impact of treatment regarding daytime sleepiness, quality of life! Ballester E, et al, AJRCCM 1999 Farre R, et al, Lancet 1999 Benson K, Hartz AJ. N Engl J Med 2000

  15. How to treat?

  16. CVD OSA Obesity

  17. Treatment of sleep apnea • Weight reduction • Gastric by-pass • CPAP • Palatal surgery • Oral devices • Tracheostomy • Drugs?

  18. Why to treat all OSA patients regardless daytime sleepiness?

  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. MORTALITY

  21. Mortality in severe OSAS patients at 5 to 7-yr follow-up (AHI 5527, age 5310 yrs, BMI 325 kg/m2 at baseline) % modified from Marti S et al, ERJ 2002

  22. Long-term cardiovascular outcomes in men with OSA with or without treatment with CPAP: an observational study Marin JM et al Lancet 2005; 365:1046-53

  23. Long-term cardiovascular outcomes in men with OSA with or without CPAP • Sleep clinic (1992-1994), PSG 1465 • Simple snorers (n=377) • OSA (n=1071) • CPAP recommended (n=667) • CPAP accepted (n=426) • Untreated severe OSA (AHI>30, n=235) • Healthy controls (n=264) individually matched with the severe untreated OSA for age and BMI (AHI<5)

  24. Variables Healthy Snorers Mild Severe CPAP men OSA OSA treatedat baseline (AHI 5-30) (AHI>30) Patients (n) 264 377 403 235 372 AHI* n/h 1 4 18 43 42 Age yrs 4950505050 BMI*kg/m230 26 28 30 31 Hypertens.* (%) 15 18 25 35 35 Diabetes (%) 7 7 7 8 8 Smokers (%) 23 23 24 25 25 Marin JM et al, Lancet 2005

  25. Cardiovascular events in men during 10 years % *** *** modified from Marin JM et al, Lancet 2005

  26. Fully adjusted Odds Ratios for cardiovascular death associated with clinical variables OR (95% CI) p Age, yrs 1.09 (1.04-1.12) 0.001 Snoring 1.03 (0.31-1.84) 0.88 Mild OSA 1.15 (0.34-2.69) 0.71 Severe OSA 2.87 (1.17-7.51) 0.025 CPAP 1.05 (0.39-2.21) 0.74 Cardiovascular disease 2.54 (1.31-4.99) 0.005 Marin JM et al, Lancet 2005

  27. OVERALL CARDIOVASCULAR DISEASE

  28. Peker et al, AJRCCM 2002; 166: 159-65

  29. HYPERTENSION

  30. OSA as a risk factor for hypertension (sleep-clinic population, n=2677) Lavie P et al; BMJ 2000;320:479-482

  31. OSA & HT in a general population Sleep Heart Health Study Cross-sectional analysis (n=6,132) Adjusted OR for HT 1.37 (95% CI 1.03-1.83) (AHI>30 versus AHI<1.5) Nieto FJ et al, JAMA 2000;283:1829-1836

  32. Incidence of HT in a general population Wisconsin Sleep Cohort Prospective 4-yr follow-up (n=893) AHI Adj. OR 95% CI 0 1 0.1-4.9 1.4 1.1-1.8 5.0-14.9 2.0 1.3-3.2 >=15 2.9 1.5-5.6 Peppard PE et al, N Engl J Med 2000;342:1378-1384

  33. Ambulatory BP after therapeutic and subtherapeutic CPAP for OSA: a randomised parallel trial • Normotensive & Hypertensive • OSAS (n=118) • More BP-reduction in hypertensives • More BP-reduction in severe OSAS Pepperell J et al, LANCET 2001; 359: 204-210

  34. CORONARY ARTERY DISEASE

  35. OSA & CAD in a general population Sleep Heart Health Study Cross-sectional analysis (n=6,132) Adjusted OR for CAD 1.27 (95% CI 0.99-1.62) (AHI>11 versus AHI<1.4) Shahar E et al, AJRCCM 2001;163:19-25

  36. Prevalence of risk factors (%) OSA & Coronary Artery Disease Peker et al, Eur Resp J 1999; 14: 179-84

  37. 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, Eur Resp J 1999; 14: 179-84

  38. Prevalence of OSA in CAD

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