- AASM - American Academy of Sleep Medicine
- ACS - Acute coronary syndrome
- AHI - Apnea-hypopnea index
- APAP - Autotitrating positive airway pressure
- BPAP - Bilevel positive airway pressure
- CPAP - Continuous positive airway pressure
- CVD - Cardiovascular disease
- DoD - U.S. Department of Defense
- EEG - Electroencephalogram
- EMG - Electromyogram
- ODI - Oxygen desaturation index
- OSA - Obstructive sleep apnea
- PAP - Positive airway pressure
- RCT - Randomized controlled trial
- RDI - Respiratory disturbance index
- REI - Respiratory-event index
- RERA - Respiratory effort-related arousal
- UPPP - Uvulopalatopharyngoplasty
- VA - Department of Veterans Affairs
- Apnea-hypopnea index (AHI) - total number of apneas and hypopneas divided by the total sleep time. In home testing where sleep is not measured, total sleep time is replaced with hours of recording time and the measure is sometimes referred to as the respiratory-event index. AHI = Apneas + Hypopneas / Total sleep time
- Autotitrating positive airway pressure (APAP) - APAP machines constantly measure airflow and using a computer algorithm, they continuously adjust the pressure applied during sleep to keep the airways open. In theory, they are supposed to offer a better treatment since the pressure required to treat OSA can vary over the course of the night and is dependent on sleep position and other factors. APAP machines can also be used to titrate PAP settings at home which can enable a patient to forego a lab-based titration study.
- Bilevel positive airway pressure (BPAP) - CPAP machines apply the same pressure throughout the breathing cycle (inspiration and expiration), whereas BPAP machines apply a lower pressure during expiration. The pressure reduction during expiration may be more comfortable for some patients, because it reduces the amount of pressure necessary for the patient to exhale.
- Central apnea - a central apnea is defined as a total cessation of airflow lasting at least 10 seconds with no detectable respiratory effort
- Continuous positive airway pressure (CPAP) - CPAP is a machine that applies pressure through a mask that covers the patient's nose, mouth, or both. The pressure applied through the mask acts as a pneumatic splint that keeps the patient's airway open during sleep. The pressure applied through a CPAP machine is the same throughout the breathing cycle in contrast to a BPAP machine where the pressure is reduced during expiration and an APAP machine that constantly adjusts the pressure.
- Home sleep study - a home sleep study is performed at home with equipment that is provided to the patient. Most home sleep studies measure airflow, respiratory effort, and oxygen saturation. Because home sleep studies do not measure sleep, they cannot directly measure the AHI. Instead, substituted leep time is replaced with monitored time in the AHI formula and this parameter, called the respiratory-event index, is for the AHI.
- Hypopnea - there are 2 definitions that are commonly used to define a hypopnea:
- 1. Reduction in airflow (≥ 30% from baseline) lasting at least 10 seconds with concurrent decrease in oxygen saturation of at least 4%
- 2. Reduction in airflow (≥ 50% from baseline) lasting at least 10 seconds with either a decrease in oxygen saturation of at least 3% or arousal from sleep
- Mixed apnea - a mixed apnea is an apnea that begins as a central apnea and ends as an obstructive apnea (i.e. respiratory effort is not present at the beginning but appears later during the episode)
- Obstructive apnea - an obstructive apnea is a total cessation of airflow lasting at least 10 seconds with persistent respiratory effort
- Oxygen desaturation index (ODI) - the ODI is defined as the number of times per hour of sleep that the blood oxygen level drops by ≥ 4% from baseline
- Polysomnography - a polysomnography is a sleep study that is typically performed in a sleep lab. During a polysomnography, the following are measured:
- Airflow through the nose is measured using a nasal cannula connected to a pressure transducer or through the nose and mouth using a thermal sensor
- Respiratory effort is measured using thoracic and abdominal inductance bands
- Oxygen hemoglobin saturation is measured using a finger pulse ox
- Snoring is measured through a microphone or through the nasal cannula-pressure transducer system
- Sleep stages and arousals are measured via an electroencephalogram (EEG), electrooculogram, and chin electromyogram (EMG)
- Leg movements are measured via an anterior tibialis EMG
- Heart rhythm is measured via a single-lead ECG
- Respiratory disturbance index (RDI) - the RDI is the same as the AHI except that it includes respiratory effort-related arousals (RERAs) along with apneas and hypopneas. RDI = Apneas + Hypopneas + RERAs / Total sleep time
- Respiratory effort-related arousal (RERA) - an RERA is defined as flattening of the inspiratory nasal pressure for ≥ 10 seconds causing an arousal from sleep but not meeting criteria for an apnea or hypopnea
- Respiratory-event index (REI) - because home sleep studies do not measure sleep, they cannot directly measure the AHI. Instead, sleep time is replaced with monitored time and the parameter is called the REI which is defined as the total number of apneas and hypopneas divided by the total monitoring time. REI = Apneas + Hypopneas / Total monitoring time
- Split-night polysomnography - during a split-night polysomnography, a normal polysomnography is performed during the first two hours of testing, and patients who demonstrate a significant amount of respiratory events are then switched to a CPAP titration protocol for the remainder of the study. If successful, the split-night polysomnography eliminates the need for a second sleep study. [1,2,5,6]
- OSA is believed to affect approximately 25% of U.S. adults. Men are twice as likely as women to have OSA, and the incidence increases with age. In one study of US adults aged 30 - 70 years, 17% of women and 34% of men had mild OSA. Moderate or severe OSA was present in 5.6% of women and 13% of men. Studies in older adults (≥ 50 years) have shown an overall prevalence of up to 60% with moderate to severe OSA being present in up to 40% of these patients.
- OSA is primarily seen in overweight individuals, but it does occur in normal weight people. In one study, the prevalence of OSA among patients aged 30 - 49 years with a BMI < 25 was 7% among men and 1.4% among women. [1,2]
- RISK FACTORS
- Obesity or overweight - by far, the most important risk factor for OSA. OSA is present in up to 40% of people with BMI ≥ 30.
- Male sex - men are affected twice as much as women
- Age - incidence of OSA increases with age
- Postmenopausal - possibly due to loss of progesterone which stimulates upper airway muscles
- Craniofacial abnormalities - abnormalities associated with OSA include elongated soft palate, shortened mandible, retro-positioned mandible, and inferior positioning of the hyoid bone
- Enlarged tonsils and/or adenoid tissue
- Acromegaly [1,2]
|Symptoms of Moderate to Severe OSA|
|Symptom||% of affected individuals|
|Nocturnal choking / gasping||52%|
|Excessive daytime fatigue||50%|
- The underlying pathology behind OSA is obstruction of the upper airways during sleep. The obstruction can occur through several mechanisms including:
- Fat deposition - Fat deposition in the tongue and pharynx causes the airway to narrow and makes it more prone to collapse during sleep
- Craniofacial abnormalities - Craniofacial abnormalities may contribute to or cause OSA. Abnormalities associated with OSA include an elongated soft palate, shortened mandible, retro-positioned mandible, and inferior positioning of the hyoid bone.
- Enlarged tonsils and/or adenoid tissue - Enlargement of the tonsils and/or adenoid tissue may cause or worsen OSA. This is the most common cause of OSA in children.
- When the airway is obstructed, intermittent hypoxemia occurs which causes loss of synchronized movement between the thorax and abdomen (paradoxical breathing), activation of the sympathetic nervous system, and arousal. The cycle repeats itself over and over again during the course of sleep.
- OSA has been associated with an increased risk of hypertension, diabetes, cardiovascular disease, atrial fibrillation, stroke and death. It's important to note that these conditions are also strongly associated with obesity, so it's unclear if OSA is causal or merely a confounder. Several large studies have found that CPAP does not affect cardiovascular outcomes which supports the latter. [1,2,5]
- OSA disease categories
- The table below gives the values that are used to diagnose OSA based on the AHI/REI. It's important to note that a normal AHI has never been determined through a cross-sectional study of asymptomatic people which means that the values are somewhat arbitrary. The cutoff value for severe OSA is based on cohort studies that showed an increased risk of hypertension for values > 30. 
|OSA Disease Categories|
|5 - 14.9||Mild|
|15 - 29.9||Moderate|
|VA/DoD 2019 OSA Clinical Practice Guidelines|
Whom to screen
- In observational studies, OSA has been associated with a number of adverse cardiovascular outcomes including cardiovascular disease, atrial fibrillation, stroke and death. Despite this, several large randomized controlled trials have now found that CPAP therapy does not have a significant effect on these events (see SAVE study and ISAACC study below). Since correcting OSA with CPAP does not improve cardiovascular outcomes, it suggests that OSA may be a marker of disease severity as opposed to causal factor.
- CPAP has been shown to improve the symptoms of daytime sleepiness, although this is an unblinded and subjective assessment. It does appear to have a modest effect on blood pressure in some hypertensive patients.
- Treatment recommendations for OSA from the AASM and VA/Dod are provided below
- Professional recommendations
- AASM 2009
- CPAP applied through a nasal (preferred), oral, or oronasal interface is the preferred treatment for all forms of OSA (mild to severe). BPAP, pressure relief, or APAP may be considered in CPAP-intolerant patients.
- Alternative therapies including oral appliances, behavioral therapy, and surgery may be considered for patients who do not tolerate/accept PAP. 
- VA/DoD 2019
- AHI/REI ≥ 30 - PAP is recommended
- AHI/REI 5 - 29.9 - PAP or mandibular advancement device
- All patients should receive counseling on behavioral and lifestyle treatment 
- Positive airway pressure (PAP)
- Mechanism - pressure applied to the airway from the device provides a pneumatic splint that keeps the airway open during sleep. The different types of PAP include CPAP, BPAP, and APAP.
- Efficacy - PAP is the most studied and preferred treatment for OSA. PAP is effective in reducing the AHI to the normal range in greater than 90% of patients when used appropriately. Acceptable adherence to PAP is typically defined as at least 4 hours of use for ≥ 5 nights a week.
- Disadvantages - the main drawback to PAP is patient discomfort and acceptance. In studies, 65 - 80% of people who start using PAP are still using it after 4 years. Side effects of PAP include discomfort, upper airway dryness, nasal congestion, and skin irritation. [1,2,5,6]
- Mandibular advancement devices
- Mechanism - a mandibular advancement device covers the upper and lower teeth and holds the mandible in an advanced position which increases upper airway volume
- Efficacy - mandibular advancement devices are not as effective as PAP, and they are generally not recommended for severe OSA. In a meta-analysis that encompassed 34 randomized controlled trials, the devices reduced the AHI by an average of 13.6.
- Disadvantages - the devices require adequate dental and periodontal structures. The devices may cause or exacerbate temporomandibular joint (TMJ) discomfort. Tooth movement may occur with long-term use. [1,2,5,6]
- Mechanism - surgery is typically recommended for nonobese patients with craniofacial abnormalities. Uvulopalatopharyngoplasty (UPPP) is the most common procedure performed, and it involves resection of the uvula and a portion of the soft palate. Maxillomandibular advancement is another procedure that is more complex and involves cutting the bones of the mandible and maxilla (surgery illustration). If the tonsils and adenoids are enlarged and obstructing the airway, adenotonsillectomy and other soft tissue procedures may be performed.
- Efficacy - in one small randomized trial (N=65), UPPP decreased the average AHI from 53.3 to 21.1 in patients with moderate to severe OSA. [PMID 23644225] Maxillomandibular advancement surgery has been shown to be very effective with an average reduction in AHI of 80% across studies.
- Disadvantages - invasive surgical procedures that carry all the risks of surgery. Post-operative pain can be significant. [1,2,5,6]
- Behavioral and lifestyle therapy
- Weight loss - in obese patients, weight loss can have a profound effect on OSA. In one trial, 125 overweight patients with OSA (average baseline weight 224 lbs | average baseline AHI 23) who lost an average of 24 pounds saw a reduction in their AHI of 9.7 events/hour. [PMID 19786682]
- Exercise - independent of weight loss, exercise has been shown to have a positive effect on OSA. In one small study, exercise improved the AHI and reduced oxygen desaturations in overweight patients with moderate to severe OSA. [PMID 22131599]
- Sleep positioning - some patients with OSA only have symptoms or have worsening of symptoms when they sleep in the supine position (on one's back). Sleeping on one's side or prone (on one's stomach) may improve or alleviate OSA. Positional OSA should be documented in a laboratory-based polysomnography before therapy is initiated. A positional device (e.g. alarm, pillow, backpack, tennis ball) should be used to help maintain the nonsupine position.
- Alcohol and CNS depressants - alcohol and drugs with CNS depressant activity (e.g. insomnia medications, opiates, benzodiazepines) may worsen OSA and should be avoided if possible [1,2,5,6]
- Upper airway stimulation
- Mechanism - In May 2014, the FDA approved the Inspire® Upper Airway Stimulation (UAS) device for the treatment of OSA. It is the first implantable device approved for the treatment of OSA. The device is comprised of a pulse generator that is implanted subcutaneously below the right clavicle. A sensor is placed in the fourth intercostal space and connected to the pulse generator. A stimulator is placed along the hypoglossal nerve just beneath the chin. The sensor detects when a breath is taken and it sends an impulse to the pulse generator. The pulse generator then sends a signal to the stimulator, and it stimulates the hypoglossal nerve. Stimulation of the hypoglossal nerve causes the tongue to move forward which helps to open the airway during inspiration (see Inspire® illustration).
- Efficacy - Approval of the Inspire® device was based on the STAR study
- The SAVE study enrolled 2717 patients with moderate-to-severe OSA and cardiovascular disease
Main inclusion criteria
- Age 45 - 75 years
- Moderate-to-severe OSA defined as an oxygen desaturation index (# of times per hour that O2 sat drops by ≥ 4% from baseline) of ≥ 12
- Diagnosis of coronary artery disease or cerebrovascular disease
Main exclusion criteria
- Severe daytime sleepiness
- Severe hypoxemia defined as O2 sat < 80% for > 10% of recording time
- Cheyne-Stokes respirations
- Average age 61 years
- Male sex - 81%
- Coronary artery disease - 51%
- Cerebrovascular disease - 49%
- Average BMI - 29
- Average oxygen desaturation index - 28
- Average AHI - 29
Randomized treatment groups
- Group 1 (1346 patients) - CPAP
- Group 2 (1341 patients) - Usual care
- All patients received advice on healthful sleep habits and lifestyle changes to minimize OSA
- Before randomization, all patients underwent a one week run-in period where they proved adherence to CPAP therapy (average use of 3 hours per night)
- CPAP was initially set in automatic mode for 1 week and thereafter fixed to the 90th percentile of pressure that was calculated by the automated positive airway pressure device from the recorded data
Primary outcome: Composite of death from any cardiovascular cause, myocardial infarction (including silent myocardial infarction), stroke, hospitalization for heart failure, acute coronary syndrome (including unstable angina), or transient ischemic attack
|Duration: Average of 3.7 years|
|Primary outcome||17%||15.4%||HR 1.10, 95% CI [0.91 - 1.32], p=0.34|
|Myocardial infarction||3.1%||2.9%||HR 1.06, 95% CI [0.68 - 1.64], p=0.80|
|Stroke||5%||5.1%||HR 0.97, 95% CI [0.69 - 1.35], p=0.84|
|Hospitalization for heart failure||1.3%||1.3%||HR 0.98, 95% CI [0.50 - 1.92], p=0.96|
|Overall mortality||3.0%||3.2%||HR 0.91, 95% CI [0.59 - 1.40], p=0.67|
|New-onset atrial fibrillation||1.6%||1.1%||HR 1.46, 95% CI [0.76 - 2.81], p=0.26|
|Change in SBP||+0.7 mmHg||+1.5 mmHg||p=0.55 for baseline adjusted difference|
|Change in DBP||-0.9 mmHg||-0.1 mmHg||p=0.05 for baseline adjusted difference|
Findings: Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease.
- The ISAACC study enrolled 1264 patients who presented to the hospital with ACS and were found to have an AHI ≥ 15 during a hospital sleep study
Main inclusion criteria
- Admitted to hospital with ACS
- AHI ≥ 15 on sleep study done during hospitalization
- Epworth Sleepiness Scale ≤ 10
Main exclusion criteria
- Previous CPAP treatment
- Central apneas > 50%
- Presence of Cheyne–Stokes respiration
- Average age 60 years
- Male sex - 84%
- Average BMI - 29
- Average AHI - 36
- Average ODI - 32
Randomized treatment groups
- Group 1 (629 patients): CPAP treatment
- Group 2 (626 patients): Usual care
- Sleep studies were performed during the first 24 - 72 hours of hospitalization for ACS. CPAP machines were titrated before patient discharge.
Primary outcome: Composite of the first cardiovascular events (cardiovascular death or nonfatal events [acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack])
|Duration: Median of 3.35 years|
|A fib or other arrhythmia||2%||3%||p=0.56|
Findings: Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence.
- The STAR trial enrolled 126 patients with moderate to severe OSA who had difficulty either accepting or adhering to CPAP
Main inclusion criteria
- Moderate to severe OSA
- Difficulty accepting or adhering to CPAP treatment
Main exclusion criteria
- BMI > 32
- AHI of < 20 or > 50 events per hour
- Central or mixed disorder ≥ 25% of all episodes
- Anatomical abnormalities preventing effective use or assessment (e.g. tonsil size ≥ 3)
- Complete concentric collapse at the retropalatal airway during sleep
- Average age 54.5 years
- Male sex - 83%
- Average BMI - 28
- Average AHI - 32
- Average ODI - 29
- Previous UPPP - 17%
Treatment - Inspire® device implantation. Follow-up sleep studies were performed at 2, 6, and 12 months.
Primary outcome: The primary outcome was the change from baseline at 12 months in the severity of obstructive sleep apnea in the study population, as assessed by means of the AHI and the ODI
|Duration: 12 months|
Findings: In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea.
- 1 - PMID 32286648 - Diagnosis and Management of Obstructive Sleep Apnea, A Review, JAMA (2020)
- 2 - PMID 30970189 - Obstructive Sleep Apnea in Adults, NEJM 2019
- 3 - PMID 23989984 - Does This Patient Have Obstructive Sleep Apnea?: The Rational Clinical Examination Systematic Review, JAMA (2013)
- 4 - PMID 32066145 - The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines, Annals of Internal Medicine (2019)
- 5 - Obstructive sleep apnea, Medscape
- 6 - PMID 19960649 - Clinical Guideline for the Evaluation, Management and Long-Term Care of Obstructive Sleep Apnea in Adults, J Clin Sleep Med (2009)