Obstructive Sleep Apnea and Hypertension

1. Obstructive Sleep Apnea and Hypertension Christine Won, M.D. Stanford Sleep Disorders Center

2. Objectives • Hypertension • Definition • Risk Factors • Significance • Causes • Treatment • Obstructive Sleep Apnea • Association with Hypertension • Physiology • Causes • Treatment • Other Cardiovascular Diseases

3. Definition of Hypertension • Normal blood pressure: systolic <120 mmHg and diastolic <80 • Pre-hypertension: systolic 120-139 or diastolic 80-89 • Hypertension:  • Stage 1: systolic 140-159 or diastolic 90-99 • Stage 2: systolic 160 or diastolic 100

4. Prevalence of Hypertension Hajjar, I, Kotchen, TA. JAMA 2003; 290:199.

5. White-Coat Hypertension Mancia, G, Parati, G, Pomidossi, G, et al, Hypertension 1987; 9:209

6. Risk Factors for Hypertension • More common and more severe in blacks • It is likely that increased salt intake is a necessary but not sufficient cause for hypertension • Excess alcohol intake increases risk • High cholesterol may also associated with the development of hypertension • Hypertension may be more common among those with certain personality traits, such as hostile attitudes and time urgency/impatience

7. Obesity and Hypertension • Obesity is associated with an increased risk of hypertension, and weight gain appears to be a main determinant of the rise in blood pressure that is commonly seen with aging • Weight loss improves blood pressure Stevens, VJ, Corrigan, SA, Obarzanek, E, et al, Arch Intern Med 1993; 153:849

8. Why is Hypertension Important? • Hypertension is associated with a number of serious adverse effects • The likelihood of developing these complications varies with the blood pressure • The increase in risk begins as the blood pressure rises above 110/75 mmHg and, at any blood pressure, is importantly affected by the presence or absence of other risk factors

9. Why is Hypertension Important? • Premature cardiovascular disease • Coronary heart disease • Heart failure • Stroke • Intracerebral hemorrhage • Chronic renal insufficiency and end-stage renal disease • Acute, life-threatening emergency

10. What Causes Hypertension? • Increased sympathetic neural activity • Increased angiotensin II activity and mineralocorticoid excess • Reduced adult nephron mass • may be related to genetic factors, intrauterine disturbance (eg, hypoxia, drugs, nutritional deficiency), and post-natal environment (eg, malnutrition, infections) • Hypertension is twice as common in those who have hypertensive parents; genetic factors account for approximately 30% of the variation in blood pressure

11. Benefit of Treating Hypertension • Antihypertensive therapy has been associated with 40 percent reduction in stroke; 25 percent in myocardial infarction; and more than 50 percent in heart failure • It is estimated that control of hypertension to below 140/90 mmHg could, in men and women, prevent 19 and 31 percent of coronary heart disease events

12. Lifestyle modifications in the management of hypertension The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, JAMA 2003; 289:2560

13. Obstructive Sleep Apnea and Hypertension • Wisconsin Sleep Cohort Study • Dose-dependent relationship between severity of sleep apnea and risk of developing hypertension • Odds for developing hypertension during a 4-8 year follow-up period compared to subjects with no apneas or hypopneas was 2.0 if AHI was 5-15, and 3.0 if AHI>15 • The Sleep Heart Health Study • A cross-sectional analysis of a large community-based multi-center population showed an increase in odds of 1.4 for hypertension when AHI > 30 compared to those with AHI < 1.5 • The Nurses’ Health Study • Increase in risk of 1.6 for the development of hypertension over an 8-year follow-up period in regular snorers compared to non-snorers

14. The Relationship between Obstructive Sleep Apnea and Hypertension • The odds of having hypertension is 37% greater in persons with obstructive sleep apnea • The odds of having hypertension is 46% greater in those who spend greater percentage of sleep time below 90% oxygen saturation Nieto, F. J. et al. JAMA 2000;283:1829-1836

15. The Relationship between Obstructive Sleep Apnea and Hypertension • Compared to those with AHI=0, the odds of having hypertension was 42% greater if AHI was 0.1-5, 2x greater if AHI was 5-15, and almost 3x greater if AHI was more than 15 per hour Peppard et al. NEJM. 2000; 342:1378-1384

16. Obstructive Sleep Apnea: Physiology

17. Obstructive Sleep Apnea: Physiology www.qeok.com/lung-cancer/asbestosis-picture.jpg

18. Obstructive Apnea Negative Intrathoracic Pressure (Mueller Maneuver) Hypoxia Hypercapnia Resumption of breathing Labile blood pressure Obstructive Sleep Apnea and Cardiovascular Effects EEG arousals • Fragmented sleep • Increased sympathetic activity

19. EEG EOG EKG SBP PAP SAO2 RESP Overnight Polysomnogram in a Patient with Obstructive Sleep Apnea Tilkian AG, Guilleminault C. Ann Intern Med. 1976 Dec;85(6):714-9

20. The Sympathetic System • Many early studies demonstrated abnormal autonomic activity in both animal models and in humans with obstructive sleep apnea: • Increased norepinephrine levels • Increased muscle sympathetic nerve activity

21. Sympathetic System: Muscle Nerve Activity • Compared muscle sympathetic nervous activity (MSNA) of blood vessels in untreated and treated OSA at baseline and after 1, 6, 12 months of CPAP • MSNA was similar during repeated measurements in the untreated group • In contrast, MSNA decreased significantly over time in patients treated with CPAP Narkiewicz et al. Circulation 1999;100:2332-2335

22. Sympathetic System: Norepinephrine • 24-hr urinary NE increased 45% in apneic (RDI>20) compared to non-apneic patients. • CPAP treatment lowered daytime plasma NE levels by 23%; Placebo had no effect on NE levels Dimsdale et al, Sleep 1995;18:377-81

23. Treating Obstructive Sleep Apnea • Several trials have demonstrated improved systolic and diastolic blood pressures with both short-term and long-term CPAP use • Regular CPAP use has also shown to improve blood pressure in patients with refractory hypertension who were requiring three or more antihypertensive medications

24. The seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends evaluating for and treating obstructive sleep apnea in adults with hypertension

25. Obstructive Sleep Apnea and other Cardiovascular Diseases www.rjmatthewsmd.com/Definitions/img/osa-fig3.gif

26. Summary • Hypertension is a serious disease that affects many people • Scientific evidence for a link between obstructive sleep apnea and hypertension is compelling • Sleep apnea is thought to contribute to hypertension by increasing sympathetic nervous system activity and causing vascular dysfunction • Animal studies have demonstrated that sleep apnea can cause hypertension • Human epidemiological studies confirm that untreated sleep apnea increases the risk of having hypertension

27. Summary • CPAP stabilizes the upper airway, preventing collapse and the acute cardiovascular and hemodynamic consequences of obstructive sleep apnea • CPAP applied over several weeks reduces both systolic and diastolic blood pressure by ~10 mm Hg. These reductions are predicted to reduce stroke risk by 56% and coronary heart disease event risk by 37% • The United States National Heart, Lung, and Blood Institute now recognizes sleep apnea as a significant and reversible cause of hypertension

28. Thank You