6/2/18 SLEEP APNEA AND ITS CARDIOVASCULAR CONSEQUENCE. Salim Surani, MD, MPH, MSHM, FACP, FCCP, FAASM

Transcription

1 SLEEP APNEA AND ITS CARDIOVASCULAR CONSEQUENCE Salim Surani, MD, MPH, MSHM, FACP, FCCP, FAASM 1

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3 SNORING PATIENT Sleep and wakefulness, both of them when immoderate constitutes disease hippocrates SRS SNORING PATIENT Bible states that Solomon s bed was guarded by 60 valliant men throughout the night for fear of death (song of solomon 3:7-8) In 1945 F. Scott Fitzgerald wrote: In the real darl night of the soul it is always three o clock in the morning since the 1800 s various epidemiological reviews have shown that peak mortality occurs early in the morning. SRS 3

4 SLEEP DISORDER Obstructive sleep apnea Central sleep apnea Insomnia Parasomnia SRS SLEEP DISORDERS Falls under following 4 categories DIMS (insomnia), disorder of initiating and maintaining sleep DOES (OSA, Narcolepsy & sleep deprivation), disorder of excessive sleeping DOSWS (jet leg, work change etc) disorder of sleep wake schedule Dysfunction associated with sleep, sleep stages, or partial arousal (parasomnias) SRS Obstructive Sleep Apnea (OSA) Apnea -absence of airflow despite persistent ventilatory effort. This is the result of pharyngeal collapse and obstruction of airway. Hypopnea - decrease of airflow by 30-50% for 10 seconds or greater (adults) with or without O2 desats Malhotra and White, Lancet,

5 OBSTRUCTIVE SLEEP APNEA AIR FLOW RESPIRATORY EFFORT SRS CENTRAL APNEA Air flow Resp effort Abd movm. SRS MIXED APNEA Air Flow Resp Effort Abd movm SRS 5

6 RESPIRATORY DISTURBANCE INDEX AHI 0-5/hour: Normal AHI 6-15/hour mild apnea AHI 16-30/hour moderate apnea AHI >30/hour Severe apnea SRS Prevalence of OSA Study Location n Age Range Wisconsin Penn Spain Prevalence of AHI>5 (95%CI) Prevalence of AHI15 (95%CI) Men Women Men Women (19-28) (15-20) (20-32) 9 (6-12) 9 Not given 7 28 (20-35) (6-11) (6-9) 14 (10-18) 4 (2-7) 2 (2-3) 7 (3-11) Overview Acute cardiovascular effects of OSA Intermediary pathophysiologic mechanisms n Sympathetic activation n Vascular endothelial dysfunction n Oxidative stress n Inflammation n Increased Coagulability n Metabolic dysregulation Cardiovascular diseases n Hypertension n Cardiac Arrhythmias n Coronary Artery Disease n Congestive Heart Failure n Pulmonary Hypertension n Stroke n Metabolic Syndrome 6

7 Normal Sleep and the Heart NREM Sleep sympathetic neural activity heart rate and CO Blood pressure ( dipping ) arrhythmogenicity REM Sleep sympathetic tone Heart rate variability, generally Blood pressure variable Sinus pauses/arrhythmia not uncommon Recordings of Sympathetic-Nerve Activity (SNA) and Mean Blood Pressure (BP) Somers V et al. N Engl J Med 1993;32 ABnormal Sleep and the Heart NREM Sleep + SDB sympathetic activity heart rate Blood pressure ( non-dipping ) arrythmogenicity REM Sleep + SDB symptathetic tone Heart rate variability Blood pressure variable arrhythmias 7

8 EEG Arousal ECG Air Apnea Δ HR Breathe Flow Sono Desaturation Re-oxygenate SaO2 Apnea Respiratory Efforts Against Obstruction Breathe Chest Wall 180 sec Acute cardiovascular consequences of OSA Related to Hypoxia Hypercapnia Increased intrathoracic pressure Arousals 8

9 Sympathetic Neural Mechanisms Intra-neural Recordings - SLEEP Normal OSA SNA RESP 200 BP Somers, J Clin Invest, 1995 Increased Sympathetic Tone During Wakefulness Somers et al, J Clin Invest, 1995 Obstructive Sleep Apnea Loss of sleep stage dependent modulation of sympathetic activity Increased tonic and phasic gain of chemoreflex related sympathetic drive 9

10 CPAP and SNA 10 sec CP Somers, J Clin Invest, 1995 Cyclic Hypoxia-Reoxygenation Reactive oxygen species/oxidative stress Mitochondrial dysfunction Reactive and oxygen nitrogen species Heat shock protein induction Apoptosis Li C & Jackson. Am J Physiol Cell Physiol, 2002;282:227. Shamsuzzaman, JAMA

11 Inflammation and CV Risk: C-Reactive Protein Ridker, Circulation 2003 Inflammation and OSA: C-Reactive Protein BMI 34 BMI 36 Shamsuzzaman AS et al. Circulation 2002;105:2462. C-Reactive Protein: OSA or Obesity? Guilleminault, Sleep,

12 CRP and OSA Punjabi NM et al. Sleep 2007;30: Vascular Endothelial Dysfunction Endothelin-1 found in OSA patients. Endothelin-1 levels correlate with oxygen desaturation and mean arterial pressure Philips et al. J. Hypertens. 17:61-66, Impaired endothelial function in OSA patients free of any other cardiac or vascular disease. Kato M et al. Circulation. 102: ,2000. Endothelial dysfunction was reversible after 4weeks of CPAP use Ip et al. AJRCCM 2004;169: Intermediary Mechanisms of Cardiovascular Disease in OSA Increased Coagulation Platelet aggregation increases in OSA. Platelet function normalizes following CPAP. Role of nocturnal catecholamines? n Bokinsky et al. Chest. 108: , Hematocrit, fibrinogen and blood viscosity are increased in OSA patients and decrease following CPAP. Predisposition to clot formation. n Wessendorf et al. Am. J. Respir. Crit. Care Med. 162:2039,

13 HEALTH CONSEQUENCES FRAGMENTED SLEEP Sleepiness Productivity School grades Motor vehicle accidents Mood changes depression Senility INTERMITTENT HYPOXIA Hypertension Stroke Coronary disease Heart failure Diabetes Obesity Metabolic syndrome PCOS Impotence Pregnancy complications Hypertension Independent risk factor Treatment of OSA improves BP control Screen for ALL new hypertensives with obesity and/or history of loud snoring 13

14 STROKE 70% of stroke victims have OSA Cause vs effect vs both? Treatment of OSA improves stroke outcome and survival 14

15 SDB and Carotid Artery Atherosclerosis in Humans Drager et al; Am J Resp Crit Care Med 2005;172:613-8 CPAP Therapy Improves Sub-clinical Atherosclerosis Drager et al; Am J Rep Crit Care Med 2007; 176:706 Effect of SDB on Stroke and Death Yaggi et al; N Engl J Med 2005;353:

16 Untreated SDB is associated with increased risk for death Young et al. Sleep 2008;31: Acute coronary syndrome 16

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20 CARDIAC ARRHYTHMIAS OSA and bradyarrhythmia Bradycardia, AV blocks, asystole can occur in 10% of OSA pts Mostly in REM and associated desaturation Occurs during the apneic episode Reversed with CPAP Recent European Multicenter polysomnographic study showed presence of OSA in 60% of pts with pacemaker 68% of pts with AV block have OSA Garrigue S et al. Circulation 2007;115: SDB: Cardiac Arrhythmias SHHS Data Mehra R et al. Am J Res Crit Care Med 2006;173:

21 SDB: Cardiac Arrhythmias Arrhythmia Type Nonsustained ventricular tachycardia Unadjusted Odds Ratio 4.64 ( ) Odds Ratio * (95% CI) Odds Ratio * (95% CI) Adjusted Adjusted for Age, Sex, for Age, Sex, BMI, CHD BMI 3.72 ( ) 3.40 ( ) Complex ventricular 1.96 (1.28 ectopy 3.00) Atrial fibrillation 5.66 ( ) 1.81 ( ) 1.74 ( ) 3.85 ( ) 4.02 ( ) Mehra R et al. Am J Res Crit Care Med 2006;173: Increased Prevalence of OSA in AFib Compared with General Cardiology Patients Gami, A. S. et al. Circulation 2004;110: OSA and Recurrence of A-Fib Pts with a-fib/flutter referred for electrical cardioversion 43 had a formal sleep study resulting in the diagnosis of OSA 79 randomly selected post-cardioversion patients matched pts without prior sleep study Kanagala, R. et al. Circulation 2003;107:

22 12 mo Recurrence AFib after DCCV Kanagala, R. et al. Circulation 2003;107: OSA and Risk of Incident Atrial Fibrillation Mayo Clinic center for sleep medicine, ,542 consecutive Olmsted County adults n No current or past history of AF n First diagnostic polysomnography yo BMI 33 9 Gami AS et al. JACC 2007;49:565 Incidence of AF by OSA Status P = Gami AS et al. JACC 2007;49:565 22

23 OSA, AHI, and O 2 desaturations are risk markers for incident AF by 5 years follow-up BMI independently predicts AF O 2 desaturation independently predicts AF Gami AS et al. JACC 2007;49:565 Take-homes about a-fib OSA is very common (48%) in patients with a-fib OSA is an independent risk factor for developing a- fib (OR = 4) A-fib patients who are cardioverted and have untreated OSA have a 2.5 X increased risk of recurrence compared with treated OSA patients Makes sense to identify and treat OSA OSA and PVCs PVCs reported in 66% of pts with OSA (0-12% in the general population) No conclusive data that OSA causes PVCs Shepard JW Jr et al. Chest 1985;88: Occurs mostly during apneic periods n When O2 sats fall below 60% May be seen more often in pts with concurrent CHF, comorbid CVD Guilleminault C et al. Am J Cardiol 1983;52:490-4 Hoffstein V. Chest 1995;106:

24 OSA and PVCs Treatment with CPAP Randomized control 1 month trial OSA and systolic dysfunction n 58% reduction in PVCs and nocturnal urinary norepinephrine concentrations Ryan CM et al. Thorax 2005;60: No evidence to support atrial overdrive pacing as a treatment for OSA. Sudden Death and OSA Patients with OSA had high risk of nocturnal SD Patients without OSA had highest SD hrs Gami, NEJM 2005 Coronary Artery Disease and OSA High prevalence of OSA in patients with CAD Prevalence 37-76% CAD present by angiography in 20-68% of patients with OSA Does it matter? 24

25 Cardiac Ischemia and OSA ST-segment depression common during apneic events in sleep of OSA patients More frequent in more severe OSA n Philip et al. Sleep. 16: , 1993 Correlate with oxygen desaturation and complaints of nocturnal angina. CPAP therapy normalizes ST depression in sleep. n Peled et al. J. Am. Coll. Cardiol. 34:1744, In a five year follow-up of patients with established CAD, higher mortality in patients with OSA (38%) compared to those without OSA (9%) n Peker et al. Am J. Respir. Crit. Care. 162:81-86, BMI 30.3 Observational Cohort >1600 men (50 yo) followed for 10.1 years 36% of patients with severe OSA refused CPAP Marin JM et al. Lancet 2005; 365: Cardiac Death After PCI 12 P= Untreated OSA 8 % 6 4 Treated OSA Months after PCI Cassar et al: JACC,

26 Pulmonary Hypertension and OSA No prospective incidence data available No relative risk data available Related more to BMI and daytime hypoxemia (lung function) Available studies in mild disease (mean PAP mm Hg) Modest treatment effects in reducing PAP Summary of Recommendations: In the evaluation of patients with PAH, an assessment of SDB is recommended. Quality of evidence: low; net benefit: small/weak; strength of recommendation: C. In the evaluation of a patient with PAH for SDB, polysomnography is recommended if OSA is suspected as the etiology, if a screening test result for OSA is positive, or if a high clinical suspicion for OSA is present. Quality of evidence: expert opinion; net benefit: intermediate; strength of recommendation: E/B. In the management of patients with OSA, routine evaluation for the presence of PAH is not recommended. Quality of evidence: low; net benefit: none; strength of recommendation: I In patients with OSA and PAH, treatment of OSA with positive airway pressure therapy should be provided with the expectation that pulmonary pressures will decrease, although they may not normalize, particularly when PAH is more severe. Quality of evidence: low; net benefit: small/weak; strength of recommendation: C. Features of "syndrome Z" Hypertension Central obesity Insulin resistance Hyperlipidaemia Obstructive sleep apnoea 26

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28 Leptin Leptin, OSA and Weight Gain Phillips BG et al. Am J Physiol Heart Circ Physiol, 2000;H

29 Platelet Aggregation Cardiovascular Actions of Leptin Inflammation Sympathetic Increased Activity Adrenergic Responsiveness Renal Increased Natriuresis Endothelial NO Angiogenesis NE Pressor Depressor 29

30 Prevalence of sleep apnea in men with erectile dysfunction Hirshkowitz, M., Karacan, I., Arcasoy, M.O., Acik, G., Narter, E.M., Williams, R.L. Sleep studies were performed on 1,025 patients complaining of erectile dysfunction. Overall prevalence of sleep apnea activity in this sample was: 43.8 percent with AI 5; 27.9 percent with AI 10; and 19.6 percent with AI 15. These results confirm that sleep apnea activity is common in men with erectile dysfunction. CPAP therapy resolved the erectile dysfunction in 13 out of 17 patients. Sleep-Disordered Breathing & School Performance in Children Identified 1 st graders performing at the bottom 10% percent of grade level Found over 20% had OSA All were offered surgery (tonsillectomy and adenoidectomy), but only half accepted All children who had surgery improved their grades, the others stayed the same Gozal, Pediatrics,

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33 Non-arteritic anterior ischemic optic neuropathy Sudden, painless, irreversible, nonprogressive visual loss Mojon et al found that twelve (71%) of their 17 patients with NAION had SAS, compared to only 3 (18%) of 17 controls (P=005) Arch Ophthalmol 120 (2002), p 57% of pts with NTG, compared to 3% of nonglaucoma patients had a positive sleep history (P=0.001). 11 out of 13 with a positive sleep history that underwent PSG were diagnosed OSA NTG = NORMAL TENSION GLAUCOMA J Glaucoma 10 (2001), pp

34 CPAP therapy CPAP PAP provides a "pneumatic splint" by delivering an intraluminal pressure that is positive with reference to the atmospheric pressure. PAP increases upper-airway cross-sectional area and volume in awake normal subjects and OSA patients with the largest change in the lateral dimensions. A second mechanism by which PAP may affect upper airway size is by increasing lung volume. The increased lung volume provides a downward traction on the trachea (tracheal tug). This action is believed to stretch upper-airway structures and increase upper-airway size. Thank you Also thanks to Dr S Subramanyian and Dr K Ramar for Providing some slides 34

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37 CPE Codes RPH: 4PXz CPHT: 2EbN THANK YOU 37