1. The Change of Sympathetic Activity During Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea Patients with and without Hypertension 于鍾傑 Chung-Chieh Yu Division of Pulmonary and Critical Care Medicine Chang Gung Memorial Hospital, Keelong

2. Cardiovascular Consequences of Obstructive Sleep apnea Hypopnea Syndrome (OSAHS) Cardiovascular event: Hypertension Peppard et al. NEJM 2000(WSCS n=709) Nieto et al. JAMA 2000(SHHS n=6,132) Increased mortality and morbidity in coronary artery disease with OSAHS Mooe et al AJRCCM 2001: 164; 1910-13 High prevalence of OSAHS in CHF(2.4X) and stroke(1-2.5X) Shahar et al. AJRCCM 2001

3. Hypothesis of Cardiovascular Consequences Chronic effect on inflammatory mediator Maillard D 1997 Wessendorf 2000 Reinhart WH 2002 Endothelium dysfunction Lavie et al 2002 Ip et al 2000 Autonomic dysfunction Somers et al J Clin Invest 1995 Narkiewicz et al 1998

4. Acute cardiovascular effects of OSAHS Normal sleep induces a fall in BP –Reduced heart rate, stroke volume, cardiac output. –Reduced peripheral resistance, sympathetic nervous system activity. OSAHS causes cyclical oscillations in the these variables due to: –Exaggerated negative intra-thoracic pressure. –Hypoxia. –Recurrent arousals.

5. Example of obstructive apnoea

6. Recurrent episodes of hypertension Somers et al J Clin Invest 1995

7. Chronic Effects Increased sympathetic nerve activity Narkiewicz et al 1998

8. Nieto FJ et al. JAMA 2000;283:1829-36. Associations of SDB with Hypertension

9. HRV analysis may represent an accurate and inexpensive screening tool in suspected OSAHS. Frederic R. et al. Circulation. 1999;100:1411-1415 ↑SDNN, VLF,LH, HF at night time. Micheal C. K. Khoo et al. Sleep 1999;22;443-51

10. CPAP treatment decreases muscle sympathetic traffic in patients with OSA. Narkiewicz K et al. Circulation. 1999;100(23):2332-5 CPAP treatment decreased HR, noradrenaline plasma level,and BP Heitmann J et al. European Respiratory Journal. 2004;23(2):255-62. CPAP treatment is effective in improving autonomic activities by way of eliminating apnea and reversing hypoxemia. Guo Xiheng et al. Chin J Tuber Respir Dis 1998;21(8): 480-3

11. Autonomic nervous system is involved in the development of hypertension. Emily B. Schroeder et al. Hypertension 2003;42:1106-11 LF was associated with incident hypertension.(low LF) Jagmeet P. et al. Hypertension 1998;32:293-97

12. Question 1. Is there sympathetic activity difference between normotensive and hypertensive patients with OSAS ? 2. How the sympathetic activity change during CPAP therapy between two group?

13. Method Retrospective study Enrolled 84 OSAHS and physician recommend CPAP therapy(consecutive one year) Eliminate 14 patients (CHF, CAD, DM, and stroke, and atrial fibrillation) HRV data ( SDNN, LF, and HF) derive from initial diagnostic PSG and second CPAP titration

14. Heart Rate Variability(HRV) Non-invasive Well establish Commercial tool

15. Heart Rate Variability(HRV) SDNN : standard deviation of all R-R intervals LF: Low frequency ( ～ 0.04 to 0.15 Hz) that are sensitive to changes in cardiac sympathetic nerve activity (LF: Both sympathetic and parasympathetic activity) HF: High frequency( ～ 0.15 to 0.4 Hz) that are synchronized to the respiratory rhythm and primarily modulated by cardiac parasympathetic innervation (HF: Parasympathetic activity) LF/HF ratio: generally considered to provide a good index of sympathetic modulation (LF/HF: sympathetic activity)

16. Summary CPAP reduce heart rate variability(SDNN) for all OSAHS pateints. The HRV has no statistic difference between normotensive and hypertensive subjects before CPAP therapy. OSAHS subjects with hypertension have greater sympathetic activity reduction( △ LF and △ LF/HF ) than normotensive during CPAP therapy.

17. OSAHS patients with HTN have greater benefit when receive CPAP therapy. OSAS patients with HTN need aggressive management.