SLEEP APNEA AND ITS

CONSEQUENCE
Salim Surani, MD, MPH, MSHM, FACP, FCCP, FAASM

SNORING PATIENT

Sleep and watchfulness, both of them

when immoderate constitutes disease
hippocrates

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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

RESPIRATORY
EFFORT

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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.

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Prevalence of OSA

Study
Location

Age
Prevalence of
Range 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

26
(20-32)

28
(20-35)

14
(10-18)

7
(3-11)

30-70

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
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pressure

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 apnea
CPAP has shown to reduce
apnea/hypopnea, daytime sleepiness
and improve neuropsychiatric function

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CPAP PROBLEM
Patient acceptability
Patient acceptability....
Patient acceptability
Average 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 effective
No 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

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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

Arousals

intrathoracic pressure

Hypoxia

Weir, NEJM, 2005

Brainstem mediated:
1. ventilation
2. sympathetic neural outflow

Sympathetic Neural Mechanisms

Intra-neural Recordings - SLEEP
Normal

OSA

SNA
RESP
200

BP 100
0

Somers, J Clin Invest, 1995

Increased Sympathetic Tone

During Wakefulness

MSNA

Somers et al, J Clin Invest, 1995

HEALTH CONSEQUENCES
INTERMITTENT HYPOXIA
FRAGMENTED SLEEP Hypertension
Sleepiness
Stroke
Productivity
Coronary disease
School grades
Heart failure
Motor vehicle
Diabetes
accidents
Obesity
Mood changes
Metabolic syndrome
depression
PCOS
Senility
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

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;353:2034

Untreated SDB is associated with increased risk for death

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

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 Arrhythmias

SHHS 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 (1.48
14.57)

3.72 (1.1312.2)

3.40 (1.0311.2)

Complex ventricular
ectopy

1.96 (1.28
3.00)

1.81 (1.162.84)

1.74 (1.112.74)

Atrial fibrillation

5.66 (1.56
20.52)

3.85 (1.0014.93)

4.02 (1.0315.74)

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

Increased Prevalence of OSA in AFib Compared with General

Cardiology Patients

Gami, A. S. et al. Circulation 2004;110:364367

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

12 mo Recurrence AFib after DCCV

Kanagala, R. et al. Circulation 2003;107:25892594

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 afib (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

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

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;106:466.

OSA and PVCs

Treatment with CPAP

Randomized control 1 month trial

OSA and systolic dysfunction

58% reduction in PVCs and nocturnal urinary norepinephrine concentrations

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

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 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

Correlate with oxygen desaturation and complaints of nocturnal angina.

CPAP therapy normalizes ST depression in sleep.

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

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.

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: 1046-53.

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

12

P=0.027

10
Untreated OSA

6
4

Treated OSA

2
0
0

12

24

36

48

60

69
85

49
68

Months after PCI

175
196

151
161

118
139

94
107

Cassar et al: JACC, 2007

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

2004

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

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.

Positive correlation of plasma leptin levels with apneahypopnea index

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

Copyright restrictions may apply.

CPAP and leptin

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 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, 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),

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. 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.

Thankyou
AlsothankstoDr
SSubramanyian andDr
KRamar for
Providingsomeslides