Sleep Disorders: A Case-based Approach LeRoy Essig, MD Rami Khayat, MD Case ROS: 30 Lbs wt gain/1year Fatigue Heart burn Nasal congestion, dry mouth Reduced concentration/memory Case 47 y/o male presents to primary doctor for annual examination Recently started on citalopram History of hypertension Family history of CAD Case Social history: School bus driver, 30 p/year Wife complains of husband snoring Meds: Lisinopril, atorvastatin, hydrochlorothiazide 1
Sleep History Struggling to stay awake during daytime 6 hours of sleep per night with a 1 hour nap in the early afternoon, 2-3 beers/night Watches TV in bed before sleep Physical Examination Exam: Weight 212, BMI 35, BP 147/87 Big uvula, nasal passages narrow, thick neck Lungs clear Heart regular, no gallop, clear lungs No peripheral edema Intact sensation and strength in LE s Sleep History Awakens 3-4 times at night to use rest room Persistent loud snoring Leg jerks and kicks, restless sleep Wife gradually sleeping in another room What problems did you identify in this patient? 2
Problems General: Poorly controlled HTN Cardiovascular risk factors Heartburn Arrange problems in order of Importance Problems Sleep Fatigue, depression Snoring, sleepiness Restless sleep/legs Dissatisfied spouse Problems in Order of Importance Sleepiness Professional driver Poorly controlled hypertension Smoking Obesity Depression Restless legs 3
Differential Diagnosis Inadequate sleep time Poor sleep hygiene Obstructive Sleep Apnea Periodic Limb Movement of Sleep/Restless Leg Syndrome Inadequately treated depression Medication side effects Daytime Sleepiness Sleep deprivation for 1 day or sleeping 2 hours less/day for a week resulted in the same driving impairment as a blood alcohol level of 0.089 g/dl (Powell, 2001). 2002 NHTSA survey of 4010 adult drivers Of the 11% who admitted to nodding off while driving in the previous year, 2/3 stated they had 6 hours of sleep the previous night Daytime Sleepiness 16% of adults experience excessive sleepiness that impairs daily functioning (Young, 2004). More than 100,000 automobile accidents each year are due to drivers falling asleep (National Highway Traffic Safety Administration). 71,000 non-fatal injuries 1500 fatalities 12.5 billion dollars in annual all-cause monetary loss Assessment of Sleepiness The Epworth Sleepiness Scale SITUATION CHANCE OF DOZING 1-Sitting and reading 2-Watching TV 3-Sitting inactive in a public place (I.e. a theater or a meeting) 4- As a passenger in a car for an hour without break 5- Lying down to rest in the afternoon when circumstances permit 6-Sitting and talking to someone 7-Sitting quietly after lunch without alcohol 8 -In a car, while stopping for a few minutes in traffic 0 = Would never doze 1 = Slight chance of dozing 2 = Moderate chance of dozing 3 = High chance of dozing 4
What is the most effective next intervention? Prevalence of Obstructive Sleep Apnea Evaluate for OSA! Improved sleep hygiene and expanded sleep alone are unlikely to reduce sleepiness if OSA is untreated OSA is linked to hypertension, cardiovascular disease, periodic limb movement and depression The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults The Wisconsin Sleep Cohort, NEJM 1993 Obstructive Sleep Apnea OSA- why should I care? If I have to care, what should I do about it? Treatment of OSA and CSA in patients with heart disease is a waste of time! Symptoms of OSA Snoring Excessive daytime sleepiness Witnessed apneas Poor memory and concentration, irritability or personality changes Other: Dry throat, morning headache, and nocturia 5
Diagnosis History and physical examination Questionnaires Pulse oximetry Portable sleep studies Polysomnography Effects of Sleep on the Upper Airway Loss of tone in genioglossus, palatal, and pharyngeal constrictor muscles Supine position and reduced lung volumes OSA-Imbalance between Dilating and Constricting Forces of the Upper Airway Dilating forces: pharyngeal muscle tone Lung volumes Constricting forces: Negative inspiratory pressure Extra luminal fat Physical Examination in OSA Neck circumference > 17 inches in males > 16 inches in females Craniofacial anatomy Inferiorly positioned hyoid bone Mandibular insufficiency Increased mid-facial height Nasal obstruction 6
LOC ROC Chin EMG C3-A2 O2-A1 EKG Nasal flow Chest Abdomen Sleep Study- Polysomnography SaO 2 Why should this patient be treated urgently? Professional driver with sleepiness Poorly controlled hypertension Cardiovascular risk Depression Quality of Life Case: Results of the Sleep Study Sleep Efficiency: 68% Wakefulness and arousal index: 37/hour Respiratory disturbance index: 42/hour Periodic Limb Movement Index: 32/hour Prospective Data From Wisconsin Sleep Cohort Study (N=913) (Young et al, Sleep 20:608, 1997) Any MVA in 5 years (n=165) Increased Relative Risk Men Women No SDB Reference category = 1.0 Snorer, RDI <5 3.4* 0.9 RDI 5-15 4.2* 0.8 RDI >15 3.4* 0.6 *Significant increase compared to reference category INCREASED RISK OF CRASHES EVEN WITH MILD OSA 7
Relationship Between Severity pf Sleep Apnea and Crash Risk (N=460, OSA) (George et al, Sleep 22:790, 1999) Crash Rate (Number/Year) 0.14 0.12 0.1 0.08 0.06 0.04 0.02 0 Only increased risk RDI >40 p<0.01 Control RDI 10-25 RDI 26-40 RDI >40 Derivation of Patient Population Used in Study of CPAP and Crashes (George, Thorax 56:508, 2001) Confirmed OSA (n=740) Driving records available (n=582) CPAP treatment (n=317) Clinic follow-up for >3 years (n=210) Does Sleep Apnea Increase Crash Rates? Answer Yes Different data about relationship between crash risk and severity of illness Severe sleep apnea is a risk factor for crashes Is mild-to-moderate sleep apnea a risk factor for crashes Not clear Does treatment reduce crash risk? Yes Association of OSA and Depression Peppard, P. E. et al. Arch Intern Med 2006;166:1709-1715. 8
The Cardiovascular Consequences of Sleep Apnea Increased Sympathetic Nerve Activity in OSA (Somers et al J Clin Invest 1995; 96:1897-1904) Components of the Cardiovascular Response to Apnea Hypoxia Increased sympathetic activity Blood pressure surge Increased respiratory effort Arousal Increased Incidence of Coronary Artery Disease in OSA Pecker et al Eur Resir J 2006 9
OSA Can Kill Patients with Coronary Disease Association of Hypertension and Sleep-Disordered Breathing -- Sleep Heart Health Study Respiratory Disturbance Index: an independent predictor of mortality in coronary artery disease Odds Ratio (OR) 2.5 2 1.5 1 0.5 0 <1.5 (Ref) 1.5-4.9 5-14.9 15-29.9 >30 RDI (episodes/hour) OR adjusted for age, sex, ethnicity OR adjusted for age, sex ethnicity, and BMI n=6440 p=0.0001 for linear trend Pecker et al. AJRCC 2005 Nieto et al, JAMA 283:1829, 2000 OSA And Hypertension 40% of patients with OSA have hypertension 50% of patients with hypertension have OSA OSA patients were more likely to be nocturnal non-dippers Treatment of OSA reduces blood pressure Association Between Sleep Apnea and Incident Hypertension During 4 Year Follow Up Period Odds Ratio (OR) for Hypertension at Follow-up 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 0 (Ref) 0.1-4.9 5.0-14.9 >15 Baseline AHI OR adjusted for baseline hypertension status OR for above + age, gender, BMI, etc. Hypertension = BP of at least 140/90 or use of anti-hypertensive medications Peppard et al, NEJM 342:1378-1384, 2000 10
Association of OSA and Type II Diabetes Reichmuth et al AJRCCM 2005 Obstructive Sleep Apnea and Stroke Young et al AJRCC 2005 Association of OSA and Type II Diabetes Reichmuth et al AJRCCM 2005 4 year odd ratio of physician diagnosed DM over 4 year of follow up Obstructive Sleep Apnea and Outcome of Stroke Mohsenin NEJM 2005 11
OSA Can Cause Heart Failure OR 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 I II III IV AHI Interquartile range CHF n=6,424 Association Between Severe OSA (AHI >30) and Arrhythmias in Sleep Heart Health Study (Mehra et al, AJRCCM, doi:10.1164/rccm.200509-1442oc) Arrhythmia Type Non-sustained ventricular tachycardia Complex ventricular ectopy Atrial fibrillation Unadjusted Odds Ratio 4.64 (1.48-14.57) 1.96 (1.28-3.00) 5.66 (1.56-20.52) Odds Ratio* (95% CI) Adjusted for Age, Sex, BMI 3.72 (1.13-12.2) 1.81 (1.16-2.84) 3.85 (1.00-14.93) Odds Ratio* (95% CI) Adjusted for Age, Sex, BMI, CHD 3.40 (1.03-11.2) 1.74 (1.11-2.74) 4.02 (1.03-15.74) E Shahar, et al, AJRCCM, 2001 BMI=body mass index; CHD=coronary heart disease *Results of logistic regression analysis with SDB as the exposure; N=338 without SDB, N=228 with SDB Higher Prevalence of Predicted OSA in Patients Presenting with AF Compared to General Cardiology Patients (Gami et al, Circ 110:364, 2004) Sudden Cardiac Death in OSA N Engl J Med 2005;352:1206-14. 12
OSA Increases Fatal and Non-fatal Cardiovascular Events (Marin et al, Lancet 365:1046, 2005) OSA Negative intrathoracic pressure Sympathetic activity Hypoxemia Systolic transmural pressure Venous return RV overload Afterload SVR Oxidative injury Endothelial dysfunction Pulmonary vasoconstriction LV afterload Impaired LV filling Arrhythmias HTN Platelet activation LV Hypertrophy RV afterload LV remodeling Atherosclerosis Worsening RV function Sudden death Diastolic dysfunction Ischemic heart disease Stroke Heart failure OSA is a Cardiovascular Risk Factor Hypertension Atherosclerosis OSA Heart Failure Arrhythmia Undiagnosed OSA Kills Patients with Cardiovascular Disease OSA causes sudden death OSA worsens atrial fibrillation OSA worsens Hypertension control OSA promotes stroke OSA worsens outcome of stroke OSA promotes arrhythmia 13
OSA is a Cardiovascular Risk Factor OSA is a cardiovascular risk factor just like high cholesterol and diabetes Certain cardiovascular risk factors are modifiable Case-Continued Patient is started on CPAP, returns after 6 weeks with: Complete resolution of snoring Remains restless in sleep Sleepiness is only partially improved Dry mouth in the morning OSA is a Cardiovascular Risk Factor Early identification and treatment of cardiovascular risk factors is the current focus of care Treatment of co-existent OSA in patients with established cardiovascular disease is critical Why didn t the treatment of OSA completely reverse sleepiness Is the patient adequately for OSA? Is the patient using CPAP long enough? Is the mask appropriately fitted? Is there mask leak? Are there other correctable causes of sleepiness? 14
CPAP Limitations Interface Mask issues, claustrophobia Mouth leaks Skin abrasion Pressure-related Intolerance of pressure, flow Rhinitis, sinusitis, headaches Assessment of Adequate treatment of OSA Hours of use per night: >4-5 hours Total Sleep time: 7-10 hours Mask fitting (noise, dry eyes, aerophagia) Number of awakening per night CPAP Limitations Equipment related Noise, smell, condensation Dryness, inadequate humidification Changes in optimal pressure within night/over time Weight gain Nasal congestion Positional Sleep stage Differential Diagnosis Inadequate sleep time Poor sleep hygiene Obstructive Sleep Apnea Periodic Limb Movement of Sleep/Restless Leg Syndrome Inadequately treated depression Medication side effects 15
Sleep Hygiene Interventions Increase sleep time Avoid Alcohol too close before bedtime Avoid TV in bed Exercise 4-5 hours before bedtime Conclusions Excessive Sleepiness is present in >16% of adults OSA is present in 5-15% middle age adults OSA increases risk of vehicle accidents OSA is a cardiovascular risk factor Case-Continued Interventions: Sleep Expansion Sleep hygiene Change Citalopram 16