SLEEP APNEA AND ITS CONSEQUENCESalim Surani, MD, MPH, MSHM, FACP, FCCP, FAASM

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SNORING PATIENT

Sleep and watchfulness, both of them when immoderate constitutes diseasehippocrates

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SNORING PATIENT

Bible states that Solomons 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 1800s various epidemiological reviews have shown that peak mortality occurs early in the morning.

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SNORING PATIENT

In US 50 million adults have difficulty in sleeping

10 million usually discuss their sleep problems with physicians

5 million receive sleeping pill prescription

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SLEEP DISORDER

Obstructive sleep apnea Central sleep apnea Insomnia Parasomnia

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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)

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OBSTRUCTIVE SLEEP APNEA

AIR FLOW

RESPIRATORYEFFORT

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CENTRAL APNEA

Air flow

Resp effort

Abd movm.

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MIXED APNEA

Air Flow

Resp Effort

Abd movm

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HYPOPNEA

Hypopnea is the reduction of air flow accompanied by 02 desaturation of 4% or more

The number of apnea and hypopnea per hour is termed the respiratory distress index (RDI) or the apnea hypopnea index (AHI)

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RESPIRATORY DISTURBANCE INDEX

RDI 0-5/hour: Normal RDI 5-20/hour: gray zone RDI > 20/hour: Apneic

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SNORING PATIENT

History: Described in 4th century B.C. by Aelianus: I am informed that Dionysis through daily gluttony and intemperance, increased to an extraordinary degree of corpulency and fatness, by reason whereof he had much adoe to take breath. Because of his obesity, he was afflicted with shortness of breath and fits of chocking. So the physicians prescribed that he should get lonf fine needles which they thrust through his ribs; and belly whenever he fell into a very deep sleep

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SNORING PATIENT

The syndrome was described by Charles Dickens in the 19th century novel Posthumous Papers of the Pickwick Club as Joe the Fat boy. The character was described as having plethora, obesity, snoring, psychological changes, and the name young dropsy which elegantly describe right heart failure.

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DEFINITION OF OSA

The upper limit of normal is five apneas/hr. Because apneas normally increase with age, an AI greater than 10/hr is pathologic.

The occurrence and severity of the disordered breathing event, the degree of disruption of sleep, and symptoms determine the need for and the type of therapy.

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DISORDERS COMMONLY ASSOCIATED WITH OBSTRUCTIVE SLEEP APNEA

Obesity Nasal Obstruction Adenoidal and Tonsillar Hypertrophy Macroglossia Retrognathia, Micrognathia Acromegaly Hypothyroidism

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PREVALENCE OF OSA

1. The incidence of OSA is not known 2. Approx. 22% of patients referred to sleep study

are diagnosed with OSA. 3. OSA may affect 2-3% of the population, although

its prevalence has been reported to range from 1% to 15% in the general population.

4. 25% to 37% of people over 65 yrs may be affected.

Prevalence of OSA

Study Location

n Age Range

Prevalence of AHI>5 (95%CI)

Prevalence of AHI15 (95%CI)

Men Women Men Women

Wisconsin 626 30-60 24 (19-28)

9 (6-12)

9 (6-11)

4(2-7)

Penn 1741 20-99 17 (15-20)

Not given 7 (6-9)

2(2-3)

Spain 400 30-70 26 (20-32)

28(20-35)

14 (10-18)

7(3-11)

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SYMPTOMS OF OSA

The typical patient is male (6:1 to 10:1), middle-age to elderly (apneas increase with age), overweight (80%), hypertensive (50-90%) who presents with a history of snoring and hypersomnolence.

As opposed to patients with obesity hypoventilation syndrome, apneics have normal daytime ABGs.

The Multiple Sleep Latency Test (MSLT) was developed to objectively evaluate excessive daytime sleepiness (EDS).

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History: Be specific

Differentiate true sleepiness from fatigue, apathy, depression, etc.

Ask specific situational questions such as: Do you fall asleep reading, watching TV, driving Try for semi-specific answer s such as: always, frequent, occasionally, rarely, or never

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HISTORY : ONSET AND COURSE

Duration of sleepiness complaint Rapidity of onset : days or weeks versus months or

years Age of onset of sleepiness Variability of sleepiness over time Family history of sleepiness

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HISTORY : SLEEP QUANTITY AND SCHEDULE Usual sleep - wake schedule Work time versus non -working variation Shift work and travel Relationship of diurnal sleepiness to nocturnal sleep

quantity Previous perceived sleep needs

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HISTORY : KNOWN DISEASES OR SLEEP DISTURBING FACTORS

Previous head trauma Diseases causing pain, for example: _Arthritis _COPD Drugs and alcohol Environmental disturbances

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HISTORY : OBSERVED BEHAVIOR

History from bed partner is very important Ask about both nocturnal and diurnal behavior _Sleepiness _Snoring _Apneas _Abnormal movements

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MORBIDITY OF OSA

Restless sleep, EDS, intellectual deterioration, personality changes, and behavioral disorders can lead to job loss and life-threatening complications for those who operate motor vehicles and equipment.

Physiologic complications: chronic hypoventilation, hypertension, pulmonary hypertension, cor pulmonale, nocturnal arrhythmias, unexplained nocturnal death.

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TREATMENT APPROACHES FOR PATIENTS WITH OSA

Medical therapy -weight loss -lateral position for sleeping -avoidance of sedative and alcohol -nasal and oral appliances -pharmacological agents * protriptyline * progesterone -oxygen -nasally applied continuous positive airway

pressure

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TREATMENT (cont.)

Surgical Therapy -Treatment of discrete obstruction -Uvulopalatopharyngoplasty -Tracheostomy -Sectioning and advancement of the hyoid -gastroplasty and gastric bypass

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Should all snorers be evaluated?

1. No symptoms or witnessed apneas-advice 2. No symptoms but witnessed apneas-advice 3. Symptoms or excessive witnessed apneas-formal

sleep study and evaluation

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Risk Factors for OSA

Gender (male/female 2:1) Obesity (>120% ideal body weight) Neck size (> 17 male, >15 female) Age (middle age highest risk) Tonsillar hypertrophy Craniofacial abnormalities Retrognathia, Micrognathia Endocrinopathies (Hypothyroidism, acromegaly) Alcohol, sedative or hypnotic use.

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Workup of OSA

Screening overnight oximetry (optional) Overnight Polysomnography (gold standard) 1st night diagnostic study 2nd night therapeutic with CPAP Split night study Ambulatory study

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Consequence of sleep apnea

Nocturnal arrhythmia Hypertension Right and Left heart failure MI Pulmonary Hypertension CVA Cognitive impairment Sexual dysfunction Accidents Death

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Delivery of Positive airway pressure

CPAP BIPAP Auto CPAP Nasal Ventilator

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CPAP

Treatment of choice Most effective noninvasive therapy for

sleep apneaCPAP has shown to reduce

apnea/hypopnea, daytime sleepiness and improve neuropsychiatric function

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CPAP PROBLEM

Patient acceptability Patient acceptability.... Patient acceptabilityAverage night time use of 4.8 hrs

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Common complaints with CPAP

Nocturnal arousals Rhinitis, Nasal irritation, and dryness Aerophagia Mask and Mouth Leaks Fascial skin discomfort Difficulty with exhalation Claustrophobia Chest and Back Pain

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Dental Appliances

Useful in patient who fail CPAP Patients with retrognathia, micrognathia Best oral appliance unknown not universally effectiveNo study on compliance or effect on sleep

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Surgery for OSA

Nasal surgery Removal of Tonsils/adenoids UPPP LAUP ? laser assisted UPP Genioiglossus advancement Maxillomandibular advancement Tracheostomy

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UPPP

Effective in 50%-60% of patients with sleep apnea

effectiveness defined liberally as a 50% reduction in RDI

Results better in those patients with retropalatal obstructions

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

Acute cardiovascular consequences of OSA

Related to Hypoxia

Hypercapnia

Increased intrathoracic pressure

Arousals

Brainstem mediated: 1. ventilation2. sympathetic neural outflow

Hypoxia

Weir, NEJM, 2005

SNA

RESP200

100

0

BP

Somers, J Clin Invest, 1995

Sympathetic Neural MechanismsIntra-neural Recordings - SLEEP

Normal OSA

Increased Sympathetic ToneDuring Wakefulness

Somers et al, J Clin Invest, 1995

MSNA

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

STROKE

70% of stroke victims have OSA

Cause vs effect vs both?

Treatment of OSA improves stroke outcome and survival

Drager et al; Am J Resp Crit Care Med 2005;172:613-8

SDB and Carotid Artery Atherosclerosis in Humans

Drager et al; Am J Rep Crit Care Med 2007; 176:706

CPAP Therapy Improves Sub-clinical Atherosclerosis

Effect of SDB on Stroke and Death

Yaggi et al; N Engl J Med 2005;353:2034

Young et al. Sleep 2008;31:1071-8

Untreated SDB is associated with increased risk for death

Acute coronary syndrome

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;115:1703-9.

SDB: Cardiac ArrhythmiasSHHS Data

Mehra R et al. Am J Res Crit Care Med 2006;173:910-916

SDB: Cardiac Arrhythmias

Arrhythmia Type Unadjusted Odds Ratio

Odds Ratio* (95% CI) Adjusted for Age, Sex,

BMI

Odds Ratio* (95% CI) Adjusted for Age, Sex, BMI, CHD

Nonsustained ventricular tachycardia

4.64 (1.4814.57)

3.72 (1.1312.2) 3.40 (1.0311.2)

Complex ventricular ectopy

1.96 (1.283.00)

1.81 (1.162.84) 1.74 (1.112.74)

Atrial fibrillation 5.66 (1.5620.52)

3.85 (1.0014.93) 4.02 (1.0315.74)

Mehra R et al. Am J Res Crit Care Med 2006;173:910-916

Gami, A. S. et al. Circulation 2004;110:364-367

Increased Prevalence of OSA in AFib Compared with General Cardiology Patients

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;107:2589-2594

Kanagala, R. et al. Circulation 2003;107:2589-2594

12 mo Recurrence AFib after DCCV

OSA and Risk of Incident Atrial Fibrillation

Mayo Clinic center for sleep medicine, 1987-2003

3,542 consecutive Olmsted County adults

No current or past history of AF First diagnostic polysomnography

49 14 yo BMI 33 9

Gami AS et al. JACC 2007;49:565

Incidence of AF by OSA Status

P = 0.002

Gami AS et al. JACC 2007;49:565

OSA, AHI, and O2 desaturations are risk markers for incident AF by 5 years follow-up

BMI independently predicts AF

O2 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

Occurs mostly during apneic periods 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;52:490-4Hoffstein V. Chest 1995;106:466.

Shepard JW Jr et al. Chest 1985;88:335-340.

OSA and PVCs

Treatment with CPAP Randomized control 1 month trial

OSA and systolic dysfunction 58% reduction in PVCs and nocturnal urinary norepinephrine concentrations

No evidence to support atrial overdrive pacing as a treatment for OSA.

Ryan CM et al. Thorax 2005;60:781-785.

Sudden Death and OSA

Patients with OSA had high risk of nocturnal SDPatients without OSA had highest SD 0600-1200 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?

Cardiac Ischemia and OSA

ST-segment depression common during apneic events in sleep of OSA patients More frequent in more severe OSA

Philip et al. Sleep. 16:558-559, 1993

Correlate with oxygen desaturation and complaints of nocturnal angina.

CPAP therapy normalizes ST depression in sleep. Peled et al. J. Am. Coll. Cardiol. 34:1744, 1999.

In a five year follow-up of patients with established CAD, higher mortality in patients with OSA (38%) compared to those without OSA (9%)

Peker et al. Am J. Respir. Crit. Care. 162:81-86, 2000.

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: 1046-53.

BMI 30.3

Conclusions: Treatment of OSA is associated with a reduction in cardiac deaths, but not in MACE or MACCE, after PCI. Screening for, and treating, OSA in patients with CAD who may undergo PCI may result in decreased cardiac death.

CP1281042-1

Cardiac Death After PCI

Cassar et al: JACC, 2007

0

2

4

6

8

10

12

0 12 24 36 48 60

%

Months after PCI175 151 118 94 69 49196 161 139 107 85 68

P=0.027

Treated OSA

Untreated OSA

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 20-25 mm Hg) Modest treatment effects in reducing PAP

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.

Summary of Recommendations:

2004

Features of "syndrome Z"

Hypertension Central obesity Insulin resistance Hyperlipidaemia Obstructive sleep

apnoea

Leptin - a hormone produced predominantly in white adipose tissue.

Leptin levels increase exponentially with increasing fat mass. Leptin inhibits the synthesis of hypothalamic neuropeptide Y

(NPY), a potent stimulator of food intake. Downregulation of NPY results in increased sympathetic

nervous system outflow and energy expenditure. Activate thyroid, growth hormone, and gonadal axes and

suppress the pituitary-adrenal axis. Directly inhibits intracellular lipid by reducing fatty-acid and

triglyceride synthesis and, concomitantly, by increasing lipid oxidation

Just blame it on LEPTIN

Obesity is a leptin-resistant state. Treatment with subcutaneous leptin reduces

weight in all mammalian species tested. Leptin-induced weight loss is completely specific

for loss of adipose tissue, whereas food restriction results in loss of both adipose tissue and lean body mass.

Copyright restrictions may apply.

Ozturk, L. et al. Arch Otolaryngol Head Neck Surg 2003;129:538-540.

Positive correlation of plasma leptin levels with apnea-hypopnea index

CPAP and leptin

Prevalence of sleep apnea in men with erectile dysfunctionHirshkowitz, 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 1st 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, 1998.

Non-arteritic anterior ischemic optic neuropathy

Sudden, painless, irreversible, non-progressive 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),

57% of pts with NTG, compared to 3% of non-glaucoma 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 GLAUCOMAJ Glaucoma 10 (2001), pp. 17

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.

ThankyouAlsothankstoDrSSubramanyian andDrKRamar forProvidingsomeslides

Sleep Apnea and its consequenceSNORING PATIENTSNORING PATIENTSNORING PATIENTSLEEP DISORDERSLEEP DISORDERSOBSTRUCTIVE SLEEP APNEACENTRAL APNEAMIXED APNEAHYPOPNEARESPIRATORY DISTURBANCE INDEXSNORING PATIENTSNORING PATIENTDEFINITION OF OSADISORDERS COMMONLY ASSOCIATED WITH OBSTRUCTIVE SLEEP APNEAPREVALENCE OF OSAPrevalence of OSASYMPTOMS OF OSAHistory: Be specificHISTORY : ONSET AND COURSEHISTORY : SLEEP QUANTITY AND SCHEDULEHISTORY : KNOWN DISEASES OR SLEEP DISTURBING FACTORSHISTORY : OBSERVED BEHAVIORMORBIDITY OF OSATREATMENT APPROACHES FOR PATIENTS WITH OSATREATMENT (cont.)Should all snorers be evaluated? Risk Factors for OSAWorkup of OSAConsequence of sleep apneaDelivery of Positive airway pressureCPAPCPAP PROBLEMCommon complaints with CPAPDental AppliancesSurgery for OSAUPPPNormal Sleep and the HeartRecordings of Sympathetic-Nerve Activity (SNA) and Mean Blood Pressure (BP)ABnormal Sleep and the HeartAcute cardiovascular consequences of OSAHypoxiaSympathetic Neural MechanismsIntra-neural Recordings - SLEEPIncreased Sympathetic ToneDuring WakefulnessHEALTH CONSEQUENCESHypertensionSlide Number 47Slide Number 49Slide Number 50STROKESlide Number 52Slide Number 53Slide Number 54Slide Number 55Slide Number 56Acute coronary syndromeSlide Number 58Slide Number 59Slide Number 60Slide Number 61Slide Number 62Slide Number 63Slide Number 64Slide Number 65Slide Number 66Cardiac ArrhythmiasOSA and bradyarrhythmiaSDB: Cardiac ArrhythmiasSHHS DataSDB: Cardiac ArrhythmiasSlide Number 71OSA and Recurrence of A-FibSlide Number 73OSA and Risk of Incident Atrial FibrillationIncidence of AF by OSA StatusSlide Number 76Take-homes about a-fibOSA and PVCsOSA and PVCsSudden Death and OSACoronary Artery Disease and OSACardiac Ischemia and OSASlide Number 83Slide Number 84Cardiac Death After PCIPulmonary Hypertension and OSASlide Number 87Slide Number 88Slide Number 89Slide Number 90Slide Number 91Slide Number 92Slide Number 93Just blame it on LEPTINSlide Number 95Slide Number 96CPAP and leptinSlide Number 98Slide Number 99Slide Number 100Slide Number 101Prevalence of sleep apnea in men with erectile dysfunctionHirshkowitz, M., Karacan, I., Arcasoy, M.O., Acik, G., Narter, E.M., Williams, R.L. Slide Number 103Sleep-Disordered Breathing & School Performance in Children Slide Number 105Slide Number 106Slide Number 107Slide Number 108Slide Number 109Slide Number 110Slide Number 111Non-arteritic anterior ischemic optic neuropathySlide Number 113Slide Number 114CPAP therapyCPAPSlide Number 117