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The Impact of OSA on Exercise: A Window Into Chronic Disease Risk

The Impact of OSA on Exercise: A Window Into Chronic Disease Risk. Trent A. Hargens, PhD Department of Kinesiology James Madison University. Outline. Background on OSA-chronic disease Physiological mechanisms of disease link Exercise Testing as a diagnostic/prognostic tool

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The Impact of OSA on Exercise: A Window Into Chronic Disease Risk

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  1. The Impact of OSA on Exercise: A Window Into Chronic Disease Risk • Trent A. Hargens, PhD • Department of Kinesiology • James Madison University

  2. Outline • Background on OSA-chronic disease • Physiological mechanisms of disease link • Exercise Testing as a diagnostic/prognostic tool • Variables of interest • Exercise responses in OSA patients • Summary

  3. Hypoxemia Intrathoracic Pressure Reoxygenation Arousals OSA Hypercapnia Sleep Deprivation Sympathetic activation Endothelial dysfunction Metabolic dysregulation Systemic inflammation Disease Mechanisms Left atrial enlargement Hypercoagulability Systemic Hypertension Renal disease Pulmonary Associated CV Disease Heart Failure Stroke Arrhythmias Myocardial infarction Sudden cardiac death Somers et al., Circulation 2008;118:1080-1111.

  4. OSA and Insulin Resistance Homeostasis model assessment index Independent of age, gender, ethnicity, smoking status, BMI, waist circumference, and sleep duration Punjabi et al., Am J Epidemiol 2004;160:521-530

  5. OSA and Heart Failure • Prevalence of OSA in CHF population estimated to be as high as 40% • Javaheri, Circulation 1998;97:2154–2159 Significantly improved LV function in CHF patients with OSA following CPAP treatment Mansfield et al., Am J RespirCrit Care Med 2004;169:361-366

  6. OSA and Heart Failure * * * * * LVEDV (ml) LVESV (ml) LVEDD (mm) LVESD (mm) EF (%) Kourouklis SP, et al, Int J Cardiol (2012), http://dx.doi.org/10.1016/j.ijcard.2012.09.101. Article in press

  7. OSA and Hypertension P for trend = 0.005 ADJUSTED FOR BMI, NECK, WHR, ALCOHOL USE, SMOKING Nieto et al., Jama 2000;283:1829-1836.

  8. OSA and Hypertension P for trend < 0.001 ADJUSTED FOR BASE-LINE HYPERTENSION STATUS, NON-MODIFIABLE RISK FACTORS, HABITUS, AND WEEKLY ALCOHOL AND CIGARETTE USE Peppard et al., N Engl J Med 2000;342:1378-1384.

  9. OSA and Cardiovascular Disease Odds ratio for cardiovascular death Marin et al., Lancet 2005;365:1046-1053.

  10. OSA and Cardiovascular Disease Odds ratio for non-fatal cardiovascular events Marin et al., Lancet 2005;365:1046-1053.

  11. OSA and Cardiovascular Disease Kaplan-Meier curves A. Fatal B. Non-Fatal Authors conclude that OSA independently increases risk for CV events Marin et al., Lancet 2005;365:1046-1053.

  12. OSA and Cardiovascular Disease Wisconsin Sleep Cohort “Mortality follow-up of the Wisconsin Sleep Cohort, comprising 20,963 person-years, indicates that severe SDB is significantly associated with a 3-fold increased all-cause mortality risk (P < 0.0008), independently of age, sex, BMI, and other potential confounders

  13. OSA Disease Mechanisms Hyperleptinemia Baroreflex Sensitivity Chemoreflex Activation RAAS Activity OSA HTN Sympathetic Activation Insulin Resistance Oxidative Stress Endothelial Dysfunction Systemic Inflammation Adapted from Wolk et al., Clinics in chest medicine 2003;24:195-205.

  14. Sympathetic Activation in OSA Heightened SNA persists during waking hours, not just during sleep. Improvements in SNA during sleep were seen in this group with CPAP Somers VK et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995;96:1897-1904.

  15. Sympathetic Activation in OSA SNA was: 1. Greater in Obese vs. lean 2. Greater in Obese + OSA vs Lean + OSA 3. Greater in OSA vs. without OSA (regardless of wt) Therefore: 1. Sympathetic activation seen in obesity is independent of OSA 2. OSA’s impact on SNA is independent of body weight, but ADDITIVE Grassi et al., Hypertension 2005;46:321-325.

  16. Exercise Question • If OSA impacts so many physiological systems, how may those adaptations manifest during acute exercise? • Does it negatively impact their ability to exercise, ability to improve health/fitness, etc? • Could changes with exercise provide prognostic or diagnostic clues as OSA risk? • Given that SO MANY OSA sufferers go undiagnosed • 93 and 82% of females and males, who would benefit from treatment, remain undiagnosed (Young et al., 1997)

  17. “Cardiopulmonary exercise testing (CPX) offers the clinician the ability to obtain a wealth of information beyond standard exercise electrocardiography testing that when appropriately applied and interpreted can assist in the management of complex cardiovascular and pulmonary disease.” Circulation. 2010;122:191-225

  18. “the addition of ventilatory gas exchange measurements during exercise testing provides a wide array of unique and clinically useful incremental information that heretofore has been poorly understood and underutilized by the practicing clinician. The reasons for this are many...”

  19. Gas Exchange Variables of Interest • Peak rate of oxygen uptake (VO2peak) • Reflects the capacity of the heart, lungs, and blood to deliver O2 to the muscles. Criterion measure of Aerobic Fitness. • VO2max = (HR x SV) x [C(a-v)O2] • Minute ventilation (VE) • Amount of air moved in and out of the lungs (Liters/min) • Ventilatory Equivalent for oxygen consumption (VE/VO2) • Volume of air you must move to consume 1 Liter of O2. • Marker of ventilatory efficiency

  20. Gas Exchange Variables of Interest • Ventilatory Equivalent for CO2 (VE/VCO2) • Volume of air that you must move to blow off 1 Liter of CO2. • Marker of ventilatory efficiency for CO2 clearance • VE/VCO2 Slope • Powerful marker of ventilatory efficiency • Slope of relationship from onset of exercise to peak • MOST research done in area of heart failure

  21. Peak VO2 responses in OSA

  22. Peak VO2 vs. VE/VCO2 Slope in CHF Peak VO2 (ml.kg-1.min-1) P1 < 13.0 P2 13-16.5 P3 16.6-21.6 P4 > 21.6 VE/VCO2 Slope V1 < 27.7 V2 27.7-34.5 V3 34.6-42.1 V4 > 42.1 Francis et al., Eur Heart J 2000

  23. Peak VO2 vs. VE/VCO2 Slope in CHF slope > 30 now considered “abnormal” Arena et al., Circulation. 2007;115:2410-2417

  24. Pathophysiological mechanisms of an elevated VE/VCO2 slope Central Decreased right sided cardiac output Increased pressure in pulmonary vasculature secondary to increased left sided pressure Compromised pulmonary vessel dilation secondary to decreased NO production Increased ventilation-perfusion mismatching High VE/VCO2 slope Heightened VE response to exercise Peripheral Abnormal chemoreceptor and ergoreceptor reflex Central Abnormal chemoreceptor reflex

  25. VE/VCO2 slope in CSA (with CHF) VO2peak did not differ between groups Artz et al., Circulation. 2003;107:1998-2003

  26. Hargens et al., 2009 Altered ventilatory responses to exercise testing in young adult men with obstructive sleep apnea. Respir Med 2009;103:1063-9.

  27. Hargens et al., 2009 VO2peak did not differ between groups

  28. Hargens et al., 2009 VE/VCO2 slope - AHI correlation: r = 0.56, P = 0.001 To date, no other studies have examined this explicitly in OSA

  29. Balady et al “During dynamic exercise, heart rate increases linearly with work rate and VO2, but the slope and magnitude of heart rate acceleration are influenced by age, deconditioning, body position, type of exercise, and various states of health and therapy, including heart transplant. Chronotropic incompetence, defined as either failure to achieve 85% of the age-predicted maximal heart rate or a low chronotropic index (heart rate adjusted to the MET level), is associated with increased mortality risk in patients with known cardiovascular disease.”

  30. Sleep Med 2007;8:160-168.

  31. Kaleth et al., 2007 “The repetitive blood pressure surges during sleep and increased sympathetic activity during wakefulness may result in the structural downregulation of cardiac Beta-adrenergic receptors and/or alter the baroreflex set point to a higher level of pressure.”

  32. Balady Subjects were without a history of heart failure or coronary revascularization and without pacemakers. 6 year follow-up in 2428 subjects N Engl J Med 1999;341:1351-1357.

  33. Attenuated HR Recovery • Also a reflection of autonomic dysfunction • Imbalance between sympathetic and parasympathetic activation

  34. Sleep 2008;31:104-110.

  35. Hargens et al., 2008 Sleep 2008;31:104-110.

  36. Hargens et al., 2008 “Attenuation of the HR recovery response in OSA may reflect predominance and/or slower withdrawal of sympathetic influence; how this pattern may be affected by parasympathetic reactivation that normally slows HR is uncertain.” Sleep 2008;31:104-110.

  37. Maeder et al., 2008 Maeder MT, Munzer T, Rickli H, Schoch OD, Korte W, Hurny C, Ammann P. Association between heart rate recovery and severity of obstructive sleep apnea syndrome. Sleep Med 2008;9:753-761.

  38. Maeder et al., 2008

  39. Kline et al., 2012 * * * Kline et al., 2012. Int J Cardiol. In press

  40. Maeder et al., 2009 • 40 subjects with OSA (AHI = 37) • ~ 8 months of CPAP treatment • Exercise test responses compared pre/post * Maeder MT, et al. Continuous positive airway pressure improves exercise capacity and heart rate recovery in obstructive sleep apnea. Int J Cardiol 2009;132:75-83.

  41. Maeder et al., 2009

  42. Other ways to assess autonomic function?

  43. Heart Rate Variability HRV is the variation of beat to beat intervals among successive heart rate cycles.

  44. Heart Rate Variability • Heart rate variability (HRV) serves as a reflection of the balance between the sympathetic and parasympathetic nervous system • Frequency-domain analysis of HRV have been established as a simple and non-invasive marker • LF = low frequency (0.04-0.15 Hz). Reflection of sympathetic/parasympathetic balance • HF = high frequency (0.15-0.40 Hz). Reflection of parasympathetic activity • LF/HF = ratio. Reflection of sympathetic/parasympathetic balance • OSA patients have demonstrated autonomic dysfunction, reflected in diminished vagal activity and heightened sympathetic activity, measured through HRV. This is seen even during normal waking hours. (At rest) • Aydin, Tex Heart Inst J 2004;31:132-6

  45. Hargens et al., 2012 • 9 High risk OSA, 16 Controls • Max cycle exercise tests • HRV assessed throughout exercise and recovery Findings suggest that heightened sympathetic activation (LF) and reduced parasympathetic activation (HF) may manifest during high intensity exercise. Further examination is warranted. At peak exercise * * Heart Rate Variability is Reduced at Peak Exercise in Individuals at Risk for Sleep Apnea. Medicine & Science in Sports & Exercise 2012;44:S163.

  46. So…GXT as a clinical tool in OSA?

  47. Methods of assessing HR recovery are heterogeneous!

  48. http://www.multibriefs.com/briefs/acsm/active11-2.htm, 2010

  49. Hargens et al., 2013 • Purpose: To examine whether measures obtained during exercise testing may aid in clinical risk stratification for OSA • 102 overweight subjects • Cycle max exercise test • Screened for possible OSA with Embletta • Logistic regression analysis with AHI > 15 criteria for OSA In press: Medicine & Science in Sports and Exercise

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