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CLINICAL FOCUS: WOMEN’S HEALTH AND SLEEP DISORDERS
Obstructive Sleep Apnea (OSA) and Excessive
Sleepiness Associated with OSA: Recognition
in the Primary Care Setting
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15
Joseph A. Lieberman III,
MD, MPH 1
1
Family Medicine, Jefferson Medical
College, Hockessin, DE
For personal use only.
Correspondence: Joseph A. Lieberman III,
MD, MPH,
Professor of Family Medicine,
Jefferson Medical College,
2 Aston Circle,
Hockessin, DE 19707.
Tel: 302-234-2228
Fax: 302-234-1203
E-mail: jlieberman@jalmd.com
© Postgraduate Medicine, Volume 121, Issue 4, July 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
Abstract: Obstructive sleep apnea (OSA) is a common and debilitating condition characterized
by recurrent episodes of upper airway obstruction, resulting in intermittent occurrence of
apnea–hypopnea. Clinical features include snoring or disturbed sleep, reduced concentration
and memory, mood disorders, and excessive sleepiness (ES). Left undiagnosed and untreated,
OSA may have detrimental consequences, including cardiovascular (CV) morbidity and mortal-
ity, decreased health-related quality of life, and increased incidence of motor vehicle accidents.
As most individuals affected by OSA will initially present in the primary care setting, primary
care physicians have the opportunity to recognize the condition and refer patients for treatment
when necessary. Management of the condition should include lifestyle changes and continuous
positive airway pressure (CPAP) treatment if required. Wakefulness-promoting agents may
be considered if ES persists despite CPAP. Effective intervention for OSA not only provides
symptomatic benefits, but also improves hypertension and reduces the risk for fatal and nonfatal
CV events associated with the condition.
Keywords: obstructive sleep apnea; excessive sleepiness; diagnosis; treatment
Introduction
Obstructive sleep apnea (OSA) is a debilitating condition caused by upper airway
collapse during inspiration while sleeping, resulting in intermittent hypoxemia, hyper-
capnia, acidosis, sympathetic nervous system activation, and arousal from sleep. As
this happens frequently throughout the night, affected individuals experience disturbed
sleep patterns and reduced sleep quality. Symptoms associated with the condition
include snoring, excessive sleepiness (ES), nocturia, morning headache, reduced con-
centration and memory, and mood disorders.1–3 Excessive sleepiness is a particularly
detrimental symptom, resulting in decreased health-related quality of life (HRQoL),
increased cardiovascular (CV) morbidity, and increased incidence of motor vehicle
accidents.4–7 Lack of sleep is believed to be the main cause of this symptom;1 however,
intermittent hypoxia may further contribute to ES by causing irreversible damage to
wake-promoting areas of the brain.8 Recognition of OSA and its associated symptoms
is extremely important to minimize many of the negative effects that the condition
may have on individuals and society.
There is currently widespread underdiagnosis and undertreatment of OSA.9 Despite
the deleterious consequences of the condition, it is estimated that approximately 80% to
90% of cases are undiagnosed.9 In the majority of cases, individuals affected by OSA
will initially present in the primary care setting, and primary care physicians (PCPs)
33
71508e
 Joseph A. Lieberman III
are therefore well placed to identify affected patients.10 This
review aims to provide guidance to PCPs in recognizing the
condition and in referring for further investigation and treat-
ment when necessary.
Obstructive Sleep Apnea
and Associated ES
Obstructive sleep apnea severity is most often defined by
the apnea–hypopnea index (AHI), a measure that reflects
the number of apnea and hypopnea events that occur per
hour.11 Mild OSA corresponds to an AHI score of 5 to 15,
moderate OSA to a score of 16 to 30, and severe OSA to a
score  30.12 Another measure that can be used is the respira-
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15
tory disturbance index, which also includes respiratory events
that disrupt sleep even though they do not technically meet
the definitions of apneas or hypopneas.
Excessive sleepiness (reported by approximately
15%–20% of patients with OSA, depending on gender)13 is
often the most debilitating symptom of OSA. It is important
for PCPs to recognize that some patients have mild OSA, with
a low AHI score, yet they experience severe ES. Conversely,
patients with OSA who demonstrate very abnormal respira-
For personal use only.
tion during sleep may experience only minimal symptoms
of ES, if any.14 The lack of a simple relationship between ES
and the severity of OSA may be due to a range of factors
that differ between individuals. An example is the presence
of comorbidities—primarily depression and diabetes—and
the degree of sleep fragmentation rather than the extent of
sleep deprivation.15,16
Prevalence
Prevalence studies indicate that 1 in 5 white adults in the
United States with an average body mass index (BMI) of
25 to 28 kg/m2 has an AHI  5 (at least mild OSA), and
1 in 15 has an AHI  15.14 Up to 5% of adults in Western
countries have OSA and ES.14,17,18 Population-based studies
suggest that the prevalence of OSA is higher in blacks than in
whites, that men are at a 2- to 3-fold greater risk than women,
and that prevalence increases steadily with age in midlife.14
For example, in the Sleep Heart Health study—a prospective
cohort study designed to investigate the link between OSA
and CV disease—the proportion of individuals with moder-
ate OSA was 1.7-fold higher among older (60–99 years)
versus younger (40–60 years) participants.14 However, there
is also evidence that the prevalence may stabilize after 65
years of age.14
There is some evidence that the prevalence of OSA
observed in the primary care setting is higher than in the
34 © Postgraduate Medicine, Volume 121, Issue 4, July 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
community,19 which may be because conditions such as
obesity and hypertension and complaints such as fatigue
are abundant in this setting. The increased prevalence of
OSA in the primary care setting results in a high demand
for services to confirm or manage OSA and associated ES.20
Progression
A wide body of evidence suggests that substantial progres-
sion of OSA can occur over relatively short periods.14,21,22
For example, in the Cleveland Family Study—a longitudinal
cohort study—among 232 participants with mild OSA at the
start of the study (AHI  5 at baseline), the AHI increased
by > 4 events per hour over a period of 5 years.14 A similar
finding was observed in the Wisconsin Sleep Cohort Study,
where an overall increase in AHI of 2.6 events per hour was
observed over the 8-year follow-up period.14 In these studies,
significant predictors of progression included excess body
weight, central obesity, CV disease, diabetes, increased age,
and habitual snoring.14
Risk Factors
Potential risk factors for OSA have been evaluated in many
studies worldwide, and it is now established that these include
excess body weight, alcohol consumption, sedative use, smok-
ing, nasal congestion, hormonal changes during menopause,
craniofacial abnormalities, and genetic predisposition.14,23
There are numerous ways in which excess body weight
may affect OSA, including alterations in the structure and
functioning of the upper airway, alterations in the relationship
between respiratory drive and load compensation, reduction in
functional capacity, and increased oxygen demands.14 Reduc-
tion in weight, either through diet or through surgery, has
been documented to improve obesity-related OSA, although
additional techniques, such as nasal continuous positive airway
pressure (CPAP), will still be required in many patients.24,25
The worldwide rise in levels of obesity26 suggests that the
prevalence of obesity-related OSA will increase in the future.
Although associations between OSA and alcohol intake
and smoking habits have been observed in many studies,27–29
the mechanisms underlying these associations are not clear.
The potential contributions of smoking and alcohol to OSA
suggest that altering these factors may improve sleep-
disordered breathing. However, there have been no studies
to date directly demonstrating improvements in OSA fol-
lowing smoking cessation or modification of alcohol con-
sumption. Acute, seasonal, and chronic nasal congestion
are also associated with OSA, possibly because of high
nasal resistance.14,30

The Burden of OSA
Comorbidities
Obstructive sleep apnea is frequently associated with a
number of common but serious clinical conditions, including
CV and cerebrovascular diseases, hypertension, metabolic
disturbances, depression, and cognitive dysfunction. The
exact pathophysiologic relationships between OSA and other
conditions are unclear, but patients presenting with such
comorbidities warrant investigation for OSA. Conversely,
early effective treatment of OSA may also contribute to
improvements in some comorbidities.
The evidence for an association between hypertension
and OSA is strong.31 It has been estimated that approxi-
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15
mately half of all patients with hypertension have OSA,
and approximately half of all patients with OSA have
hypertension.32 It is now widely recognized that OSA is
an important risk factor for hypertension, independent of
excess body weight and other confounding factors.9,33,34
There is also some evidence that ES may contribute to the
pathogenesis of hypertension.35 Patients with OSA also
have an increased prevalence of congestive heart failure,36
coronary artery disease,37 myocardial infarction, nocturnal
For personal use only.
angina, myocardial ischemia,38–40 arrhythmias,38,41,42 and
sudden cardiac death,43 as well as increased susceptibility
to thrombotic and embolic cardiac44 and cerebrovascular
events.45,46 Excessive sleepiness accompanying OSA has also
been shown to be independently associated with decreases
in cardiac function.47 It is not clear, however, whether these
increases in CV morbidity and mortality are independent
of the increased incidence of hypertension associated with
OSA.36,48–50 Importantly, effective treatment of OSA using
CPAP has been demonstrated to reduce hypertension51 as
well as decrease the risk of fatal and nonfatal CV disease.52
There is also evidence suggestive of associations
between OSA and metabolic syndrome, insulin resistance,
and type 2 diabetes. However, independent associations have
not been fully established due to the confounding effects of
comorbid conditions such as obesity.53 Breathing-related
sleep disorders have also been linked with depression,54,55
which may lead to lower overall HRQoL for individuals
with OSA.56 Importantly, effective management of OSA can
provide long-term amelioration of depressive symptoms.57
Patients with OSA often report neurologic side effects such
as headaches, sleepiness, and fatigue.58 Global intellectual
dysfunction and deficits in motor function, short- and
long-term memory, and concentration have also been
reported.29,59,60 These symptoms may result from sleep
fragmentation and resultant sleepiness, but may also relate to
© Postgraduate Medicine, Volume 121, Issue 4, July 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
OSA and ES: Recognition in Primary Care
neural damage due to intermittent hypoxia. Neurocognitive
symptoms may have far-reaching consequences, negatively
affecting HRQoL and increasing the risk of accidents. In
addition, reduced cognitive function concomitant with
OSA may reduce a patient’s ability to gain or maintain
employment. The extent to which these symptoms can be
reversed through treatment is not clear.
Health-Related Quality of Life
Many studies have observed that OSA negatively affects
HRQoL. For example, HRQoL dimensions of the Medical
Outcomes Study: 36-Item Short-Form Health Survey
(SF-36) are influenced in patients with sleep-related breathing
disorders compared with unaffected individuals. 5,61,62
Excessive sleepiness associated with OSA is thought to be
central to this decline in HRQoL, as it impacts a patient’s
general perception of their emotional and physical health and
can also impair social interaction.5 In a study conducted by
Sforza et al5 in patients with OSA, daytime sleepiness was
observed to contribute more significantly to impairment in all
domains of the SF-36 than sleep-disordered breathing.
Accidents
Several studies have shown an association between OSA and
the risk of motor vehicle accidents.6,7 It is estimated that in
2000, more than 800 000 drivers in the United States were
involved in OSA-related motor vehicle accidents at a cost
of 1400 lives.63 Excessive sleepiness is considered to be the
major contributor to these accidents; one-fourth of individu-
als with untreated OSA report falling asleep while driving.64
It is possible that cognitive impairment associated with OSA
may also contribute to the increased occurrence of accidents,
although this has not been demonstrated directly. Obviously
the increased potential for motor vehicle accidents resulting
from OSA has important legal implications for both private
and commercial drivers.65
Obstructive sleep apnea and ES are also believed to
contribute to an increased incidence of accidents in the
workplace. Individuals with OSA were found to be at higher
risk of being involved in an occupational accident when
compared with a reference group from the general popula-
tion (odds ratios of 1.5 and 6.3 for men and women, respec-
tively).66 The increased rate of accidents is likely to be due to
reduced wakefulness and vigilance and a lack of attention.66
Economic Impact
The costs of untreated OSA have been addressed in several
studies. In a study of data collected between 1991 and 1994
35
 Joseph A. Lieberman III

in the United States, mean annual medical costs before diag- Figure 1. Risk factors, presenting symptoms, and comorbidities associated with
obstructive sleep apnea.
nosis of OSA were $2720 compared with $1384 for age- and
gender-matched controls (P  0.01).67 Regression analysis
showed that annual medical costs were significantly related
to the severity of OSA, even after adjusting for age, gender,
and BMI (P 0.05). The authors concluded that untreated
OSA may be responsible for $3.4 billion of additional medical
costs per year in the United States. Similarly, Ronald et al68
observed that patients with OSA used approximately twice as
many health care services (as defined by physician claims and
overnight stays in hospital) compared with control patients
during the 10 years before initial diagnosis. In the 10-year
period examined in the study, physician claims for patients
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15

with OSA were C$686 365 (C$3972 per patient) compared

with C$356 376 (C$1969 per patient) for controls. Use of
health services was significantly higher in 7 of the 10 years
before diagnosis, and the patients with OSA had more over-
night hospitalizations than controls.
There are also obvious economic consequences from road
traffic accidents associated with OSA and ES. Sassani et al63
found that while the annual cost of screening and treating
patients with OSA in Canada is approximately C$3.18 billion,
For personal use only.

collision costs for accidents caused by patients with OSA

amounted to approximately C$15.9 billion annually.
The authors estimated that these collision costs could be
reduced by C$11.1 billion annually following treatment.63
Occupational accidents and decreased work productivity
will have further cost implications.66,69
The economic costs, in terms of road traffic and work-
place accidents associated with untreated OSA and associ-
ated ES, together with the impact on health care utilization
costs, provide a strong rationale for the early diagnosis and
effective treatment of this condition.
Diagnosis of OSA
The PCP can play a key role in early diagnosis by being
vigilant for the symptoms of OSA and for conditions that
are often associated with OSA. Delayed diagnosis and treat-
ment of OSA and ES can result in a considerable burden to
patients, both in terms of symptoms and the effects that these
symptoms have on HRQoL.70
Management of OSA and its symptoms begin with
recognition, which is dependent on patient report or physi-
cian questions about risk factors, presenting symptoms,
and comorbidities (Figure 1). In the primary care setting,
patients are unlikely to present with a clear complaint of OSA
symptoms. Questioning the patient on the key symptoms of
OSA (snoring and ES) is a simple initial step, although the
physician needs to be aware that many patients may have
minimal or no symptoms14 and that patients often describe
sleepiness as “fatigue,” “tiredness,” or “lack of energy.”
The patient’s bed partner is also a valuable source of informa-
tion about the patient’s sleep pattern. Excessive sleepiness
may accompany a variety of disorders, including some types
of insomnia, neurologic and circadian rhythm disorders, and
can be a side effect of medication or a result of poor sleep
habits. These potential causes also need to be considered.
The Epworth Sleepiness Scale (ESS)71 can be used to help
assess the level of daytime sleepiness. If OSA is suspected
based on preliminary findings, further investigation into the
patient’s sleep behavior should be instigated by referring the
patient for sleep testing (Figure 2).
Formal diagnosis of OSA can only be achieved through
the use of polysomnography; however, in-home, unattended,
portable recording may be used in situations where polysom-
nography is not available or if patients decline to attend a
sleep laboratory. The American Academy of Sleep Medicine
(AASM) has issued guidance on the use of a home sleep test
to help detect OSA in select groups of adults.72 The AASM
guidelines stress that such tests are only recommended for
adults aged 18 to 65 years who have a high pretest prob-

36 © Postgraduate Medicine, Volume 121, Issue 4, July 2009, ISSN – 0032-5481, e-ISSN – 1941-9260

Figure 2. Diagnostic and treatment algorithm for obstructive sleep apnea.
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15
For personal use only.
Abbreviations: BiPAP, bilevel positive airway pressure; CPAP, continuous positive airway pressure; ESS, Epworth Sleepiness Scale; OSA, obstructive sleep apnea; PAP, positive
airway pressure; VPAP, variable positive airway pressure.
ability of moderate-to-severe OSA and no comorbid medical
conditions, and the assessment must be overseen by a sleep
specialist. Excessive sleepiness may also be objectively
assessed at a sleep disorders unit, using tests such as the
Multiple Sleep Latency Test (MSLT) and Maintenance of
Wakefulness Test (MWT).
Management of OSA
Lifestyle Changes
Once OSA has been confirmed, its management should begin
with lifestyle changes that could improve the condition.
There is widespread evidence that weight loss can improve
OSA in overweight patients.73 Unfortunately, although
effective in improving OSA, it is important that PCPs are
aware that weight loss rarely cures this sleep disorder with-
out the addition of classical interventions, such as CPAP.24
Furthermore, to date there have been no studies assessing
© Postgraduate Medicine, Volume 121, Issue 4, July 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
OSA and ES: Recognition in Primary Care
the long-term effects on the severity of OSA of popular
methods of weight loss, such as bariatric surgery. Avoidance
of nocturnal sedatives, cessation of evening alcohol inges-
tion, and avoidance of the supine position during sleep are
also initial actions that may provide benefits in mild OSA.
External nasal dilator strips, internal nasal dilators, and
lubricant sprays may reduce snoring, but there is no evidence
that they help to treat OSA. Indeed, such interventions
could delay recognition of OSA by masking snoring—a key
symptom associated with the condition.
Continuous Positive Airway Pressure
If initial lifestyle changes do not provide relief from OSA,
additional interventions should be considered. The most
common treatment option for OSA is nasal CPAP, in which
positive air pressure is continuously applied during the
sleep cycle, keeping the airway patent. A meta-analysis
37
 Joseph A. Lieberman III
of randomized trials of  2 weeks duration comparing
nocturnal CPAP with an inactive control or oral appliances
indicated that CPAP is effective in reducing ES and improv-
ing quality-of-life measures in patients with moderate and
severe OSA.51 There is also evidence that CPAP reduces
systolic and diastolic blood pressures and reduces the risk
of CV events in patients with OSA.51,52 Some patients find
that the constant pressure setting of CPAP is unsuitable
for them, in which case bilevel positive airway pressure or
variable positive airway pressure (VPAP) machines can be
used. Bilevel positive airway pressure and VPAP machines
provide different inspiratory and expiratory pressures,
which can be altered depending on the individual’s needs
Postgraduate Medicine Downloaded from informahealthcare.com by Nyu Medical Center on 07/31/15
and results obtained during a sleep study. A recent review
found that CPAP for OSA is an extremely efficient use of
health care resources and compares favorably with other
commonly funded medical therapies.74
A number of patients complain about persistent ES despite
CPAP intervention. In these cases, another clinical history
should be taken to confirm the initial diagnosis of OSA, to
check CPAP adherence, and to exclude associated condi-
tions such as poor sleep hygiene, depression, narcolepsy,
For personal use only.
and idiopathic hypersomnia. Adherence with CPAP is poor,
often because of discomfort or irritation to the mouth and
nose. The PCP can play a key role at this stage by identify-
ing reasons for nonadherence and encouraging the patient
to persist with therapy. Supplemental oxygen and positional
therapy may benefit subsets of patients. Pharmacotherapy
may be considered if ES persists.
Oral Appliances
Several types of oral appliances are available, including
mandibular advancement devices and tongue-retaining
devices. Such devices need to be fitted by suitably qualified
dental specialists. The AASM currently recommends the use
of oral appliances in patients with mild-to-moderate OSA
who prefer not to use or do not respond to CPAP.75 Oral
appliances have been demonstrated to improve AHI scores
and ES and may be beneficial in lowering blood pressure.76,77
In general, oral appliances are less effective than nasal CPAP
at reducing respiratory disturbances in affected individuals,
however, some patients prefer oral appliances over CPAP,
possibly because they offer a more convenient means of
controlling OSA.51
Surgery
There are a number of possible upper airway surgical
procedures that aim to treat OSA by relieving obstruction.78
38 © Postgraduate Medicine, Volume 121, Issue 4, July 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
The most commonly performed is uvulopalatopharyngo-
plasty, which involves removing parts of the uvula and soft
palate as well as trimming of the tonsillar pillars and remov-
ing the tonsils. However, this method has a success rate of
only about 40%, and the efficacy appears to diminish over
time following the surgery.79 In general (with the exception
of tracheotomy), surgical procedures are less effective than
CPAP,79 and there is limited clinical evidence to support their
use in patients with OSA.78
Pharmacotherapy
No pharmacotherapies are available for the treatment of
OSA. However, up to half of patients with OSA experience
residual ES despite effective CPAP treatment80 and these
patients may benefit from adjunctive pharmacotherapy. At
present, modafinil and armodafinil (nonamphetamine-based
wakefulness-promoting agents) are the only pharmacothera-
pies approved by the US Food and Drug Administration for
ES associated with OSA.81,82 Modafinil is recommended by
the AASM as an adjunct to standard treatment, such as CPAP,
in cases of persistent ES.81 The precise mechanism of action of
these agents remains to be elucidated, but it appears that they
strongly activate nerve cells in the hypothalamus that have
been implicated in the control of wakefulness.83 Randomized
clinical trials have shown modafinil and armodafinil to be
effective in improving daytime sleepiness as measured
using the ESS, the MSLT, and the MWT.84–90 In addition,
modafinil has been shown to improve HRQoL in patients
with OSA experiencing residual ES.87 Modafinil is generally
well tolerated, with the majority of side effects being mild to
moderate in severity, transient, and mostly occurring in the
first month of treatment.87 It should be remembered, however,
that modafinil is not a replacement for CPAP or other devices
that improve airflow. If prescribed, careful counseling and
follow-up are required so that the patient understands the
need to persist with CPAP while taking modafinil.
Conclusion
Primary care is the principal clinical setting in which to
recognize and screen for OSA and to monitor its treatment.
Obstructive sleep apnea is a highly prevalent and significant
medical condition that is currently widely underdiagnosed
and undertreated. Of the many symptoms associated with
OSA, ES is particularly debilitating, having a negative
impact on patient HRQoL and daily functioning. Obstructive
sleep apnea with or without ES is associated with a range of
comorbid conditions, such as hypertension, depression, and
CV disease. Untreated OSA and associated ES are likely to

have a considerable economic impact on the individual and
on society.
Lifestyle changes, such as weight loss, and interventions,
such as CPAP, are effective in many cases of OSA and ES.
Effective intervention provides symptomatic benefits, but
may also improve hypertension and reduce the risk for fatal
and nonfatal CV events in patients with OSA. Wakefulness-
promoting agents may be used as an adjunct to CPAP in
patients who continue to experience ES, providing they are
counseled and monitored for compliance with their CPAP
therapy.
Acknowledgments
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Editorial assistance was provided by Anthemis Consulting
Ltd., with financial support from Cephalon, Inc. The author
received no financial remuneration and retained full editorial
control over the content of the paper.
Conflict of Interest Statement
Joseph A. Lieberman III, MD, MPH discloses conflicts of
interest with sanofi-aventis, Somaxon, Takeda, and Wyeth.
For personal use only.
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