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Sleep Disorders: A Case-based Approach

LeRoy Essig, MDRami Khayat, MD

Case• 47 y/o male presents to primary doctor

for annual examination

• Recently started on citalopram

• History of hypertension

• Family history of CAD

• ROS: 30 Lbs wt gain/1year

Fatigue

Heart burn

Nasal congestion, dry mouth

Reduced concentration/memory

Case

• Social history: School bus driver, 30 p/year

• Wife complains of husband snoring

• Meds: Lisinopril, atorvastatin, hydrochlorothiazide

Case

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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

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

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

What problems did you identify in this patient?

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• General:Poorly controlled HTNCardiovascular risk factorsHeartburn

Problems

• SleepFatigue, depressionSnoring, sleepinessRestless sleep/legsDissatisfied spouse

Problems

Arrange problems in order of Importance

• SleepinessProfessional driver

• Poorly controlled hypertension• Smoking• Obesity• Depression• Restless legs

Problems in Order of Importance

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• Inadequate sleep time• Poor sleep hygiene• Obstructive Sleep Apnea• Periodic Limb Movement of

Sleep/Restless Leg Syndrome• Inadequately treated depression• Medication side effects

Differential Diagnosis

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 injuries1500 fatalities12.5 billion dollars in annual all-cause monetary loss

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

Assessment of SleepinessThe Epworth Sleepiness Scale

SITUATION CHANCE OF DOZING

1-Sitting and reading2-Watching TV3-Sitting inactive in a public place (I.e. a theater or a meeting)4- As a passenger in a carfor an hour without break5- Lying down to rest in the afternoon when circumstances permit6-Sitting and talking to someone7-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 dozing2 = Moderate chance of dozing 3 = High chance of dozing

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What is the most effective next intervention?

• Evaluate for OSA!Improved sleep hygiene and expanded sleep alone are unlikely to reduce sleepiness if OSA is untreatedOSA is linked to hypertension, cardiovascular disease, periodic limb movement and depression

• 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 !

Obstructive Sleep Apnea

Prevalence of Obstructive Sleep Apnea

The Occurrence of Sleep-Disordered Breathing among Middle-Aged AdultsThe Wisconsin Sleep Cohort, NEJM 1993

Symptoms of OSA• Snoring• Excessive daytime sleepiness• Witnessed apneas• Poor memory and concentration,

irritability or personality changes• Other: Dry throat, morning headache,

and nocturia

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Diagnosis• History and physical examination• Questionnaires• Pulse oximetry• Portable sleep studies• Polysomnography

OSA-Imbalance between Dilating and Constricting Forces of the

Upper Airway• Dilating forces:

pharyngeal muscle toneLung volumes

• Constricting forces:Negative inspiratory pressureExtra luminal fat

Effects of Sleep on the Upper Airway• Loss of tone in genioglossus, palatal,

and pharyngeal constrictor muscles

• Supine position and reduced lung volumes

Physical Examination in OSA

• Neck circumference> 17 inches in males

> 16 inches in females• Craniofacial anatomy

Inferiorly positioned hyoid boneMandibular insufficiency Increased mid-facial height

• Nasal obstruction

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LOC

ROCChin EMG

C3-A2O2-A1

EKGNasal flow

ChestAbdomen

SaO2

Sleep Study-Polysomnography

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

Why should this patient be treated urgently?

• Professional driver with sleepiness• Poorly controlled hypertension• Cardiovascular risk• Depression• Quality of Life

Prospective Data FromWisconsin Sleep Cohort Study (N=913)

(Young et al, Sleep 20:608, 1997)

Any MVA in 5 years (n=165)

Increased Relative RiskMen Women

No SDB Reference category = 1.0Snorer, RDI <5 3.4* 0.9RDI 5-15 4.2* 0.8RDI >15 3.4* 0.6

*Significant increase compared to reference categoryINCREASED RISK OF CRASHES EVEN WITH MILD OSA

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Relationship Between Severity pfSleep Apnea and Crash Risk (N=460, OSA)

(George et al, Sleep 22:790, 1999)

p<0.01

Only increased risk RDI >40

0

0.02

0.04

0.06

0.08

0.1

0.12

0.14

Control RDI 10-25 RDI 26-40 RDI >40

Cra

sh R

ate

(Num

ber/Y

ear)

Does Sleep Apnea IncreaseCrash Rates?

AnswerYes• 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

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)

Peppard, P. E. et al. Arch Intern Med 2006;166:1709-1715.

Association of OSA and Depression

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The Cardiovascular Consequences of Sleep Apnea

Components of the Cardiovascular

Response to Apnea• Hypoxia

• Increased sympathetic activity

• Blood pressure surge

• Increased respiratory effort

• Arousal

Increased Sympathetic Nerve Activity in OSA(Somers et al J Clin Invest 1995; 96:1897-1904)

Increased Incidence of Coronary Artery Disease in OSA

Pecker et al Eur Resir J 2006

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OSA Can Kill Patients with Coronary Disease

Pecker et al. AJRCC 2005

Respiratory Disturbance Index: an independent predictor of mortality in coronary artery disease

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

0

0.5

1

1.5

2

2.5

<1.5(Ref)

1.5-4.9 5-14.9 15-29.9 >30

RDI (episodes/hour)

Odd

s R

atio

(OR

) OR adjusted for age, sex,ethnicityOR adjusted for age, sexethnicity, and BMI

Association of Hypertension and Sleep-Disordered Breathing -- Sleep

Heart Health Study

n=6440p=0.0001 for lineartrend

Nieto et al, JAMA 283:1829, 2000

00.5

11.5

22.5

33.5

44.5

5

0 (Ref) 0.1-4.9 5.0-14.9 >15Baseline AHI

Odd

s R

atio

(OR

) for

H

yper

tens

ion

at F

ollo

w-u

p

OR adjusted for baselinehypertension statusOR for above + age,gender, BMI, etc.

Association Between Sleep Apnea and Incident Hypertension During 4 Year Follow Up Period

Hypertension = BP of at least 140/90 or use of anti-hypertensive medications

Peppard et al, NEJM 342:1378-1384, 2000

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Association of OSA and Type II DiabetesReichmuth et al AJRCCM 2005

Association of OSA and Type II DiabetesReichmuth et al AJRCCM 2005

4 year odd ratio of physician diagnosed DM over 4 year of follow up

Obstructive Sleep Apnea and Stroke

Young et al AJRCC 2005

Obstructive Sleep Apnea and Outcome of Stroke

Mohsenin NEJM 2005

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OSA Can Cause Heart Failure

E Shahar, et al, AJRCCM, 2001

00.5

11.5

22.5

33.5

44.5

5

I II III IV

AHI Interquartile range

OR CHF

n=6,424

Higher Prevalence of Predicted OSA in Patients Presenting with AF Compared

to General Cardiology Patients(Gami et al, Circ 110:364, 2004)

Association Between Severe OSA (AHI >30) and Arrhythmias in Sleep Heart Health Study

(Mehra et al, AJRCCM, doi:10.1164/rccm.200509-1442OC)

4.02(1.03-15.74)

3.85(1.00-14.93)

5.66(1.56-20.52)

Atrial fibrillation

1.74(1.11-2.74)

1.81(1.16-2.84)

1.96(1.28-3.00)

Complex ventricular ectopy

3.40(1.03-11.2)

3.72(1.13-12.2)

4.64(1.48-14.57)

Non-sustained ventricular tachycardia

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

CHD

Odds Ratio* (95% CI)

Adjusted for Age, Sex, BMI

Unadjusted Odds Ratio

Arrhythmia Type

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

Sudden Cardiac Death in OSA

N Engl J Med 2005;352:1206-14.

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OSA Increases Fatal and Non-fatal Cardiovascular Events

(Marin et al, Lancet 365:1046, 2005)

OSA is a Cardiovascular Risk Factor

Heart FailureArrhythmia

HypertensionAtherosclerosis

OSA

Pulmonary vasoconstriction

Worsening RV function

OSA

Sympathetic activity HypoxemiaNegative

intrathoracic pressure

Oxidative injuryEndothelial dysfunction

Afterload

SVR

RV afterload

Atherosclerosis

Ischemic heart disease

HTN

Arrhythmias

Diastolic dysfunction

Systolic transmural pressure

LV afterload

Venous return

RV overload

Impaired LV filling

Heart failure

Sudden death

Stroke

LVHypertrophy

LV remodeling

Plateletactivation

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

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OSA is a Cardiovascular Risk Factor

• OSA is a cardiovascular risk factor just like high cholesterol and diabetes

Certain cardiovascular risk factors are modifiable

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

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

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?

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CPAP Limitations• Interface

• Mask issues, claustrophobia• Mouth leaks• Skin abrasion

• Pressure-related• Intolerance of pressure, flow • Rhinitis, sinusitis, headaches

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

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

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

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Sleep Hygiene Interventions

• Increase sleep time• Avoid Alcohol too close before

bedtime• Avoid TV in bed• Exercise 4-5 hours before bedtime

Case-Continued• Interventions:

Sleep ExpansionSleep hygieneChange Citalopram

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