- ACRONYMS
- 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
- USPSTF - U.S. Preventive Services Task Force
- VA - Department of Veterans Affairs
- DEFINITIONS
- Apnea - an apnea is a total cessation of airflow lasting at least 10 seconds. Apneas may be obstructive, central, or mixed.
- Apnea-hypopnea index (AHI) - AHI is the total number of apneas and hypopneas divided by the sleep time in hours. 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 in hours
- Autotitrating positive airway pressure (APAP) - APAP machines, which constantly measure airflow, use a computer algorithm to continuously adjust pressures during sleep. In theory, they improve treatment since pressure requirements vary during the night and depend on sleep position and other factors. APAP machines can also be used to titrate PAP settings at home, enabling the patient to forego a lab-based titration study.
- Bilevel positive airway pressure (BPAP) - BPAP machines apply a lower pressure during expiration, whereas CPAP machines apply the same pressure during inspiration and expiration. The pressure reduction during expiration may be more comfortable for some patients because it reduces the amount of force needed to exhale.
- Central apnea - a central apnea is a total cessation of airflow lasting at least 10 seconds with no detectable respiratory effort
- Continuous positive airway pressure (CPAP) - a CPAP machine applies pressure through a mask that covers the patient's nose, mouth, or both. The pressure acts as a pneumatic splint that keeps the patient's airway open during sleep. CPAP exerts the same pressure during inspiration and expiration; this differs from BPAP, which reduces pressure during expiration, and APAP, which constantly adjusts pressure.
- Home sleep study - for a home sleep study, a patient is provided equipment that measures airflow, respiratory effort, and oxygen saturation. Unlike studies performed in labs, actual sleep time is not measured, so monitored time is substituted for sleep time in the apnea-hypopnea index.
- 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 begins as a central apnea and ends as an obstructive apnea, meaning respiratory effort is not present at the beginning of the episode but appears later
- Obstructive apnea - an obstructive apnea is total cessation of airflow lasting at least 10 seconds with persistent respiratory effort
- Oxygen desaturation index (ODI) - the ODI is the number of times per hour of sleep that the blood oxygen level drops by ≥ 4% from baseline
- Polysomnography - polysomnography is a sleep study performed in a specialized facility where the following is monitored:
- Airflow is monitored using a nasal cannula connected to a pressure transducer. Alternatively, a thermal sensor can detect airflow in the nose and mouth.
- Respiratory effort is measured using thoracic and abdominal inductance bands
- Oxygen hemoglobin saturation (pulse ox)
- Snoring is detected through a microphone or the nasal cannula-pressure transducer system
- Sleep stages and arousals are monitored with an electroencephalogram (EEG), electrooculogram, and chin electromyogram (EMG)
- Leg movements are detected with an anterior tibialis EMG
- Heart rate and rhythm
- Respiratory disturbance index (RDI) - the RDI is the same as the apnea-hypopnea index (AHI) except that it includes respiratory effort-related arousals (RERAs) along with apneas and hypopneas. RDI = (Apneas + Hypopneas + RERAs) / Total sleep time in hours
- Respiratory effort-related arousal (RERA) - a RERA is a flattening of the inspiratory nasal pressure for ≥ 10 seconds, causing 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 calculate a true apnea-hypopnea index (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 in hours. REI = (Apneas + Hypopneas) / Total monitoring time in hours
- 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]
- PREVALENCE
- OSA is believed to affect approximately 25% of U.S. adults. Men are affected twice as much as women, and the incidence increases with age. In a study of U.S. adults aged 30 - 70, 17% of women and 34% of men had mild OSA, while moderate or severe OSA was present in 5.6% and 13%, respectively. Studies in older adults (≥ 50 years) have shown an overall prevalence of up to 60%, with moderate to severe OSA affecting 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% in men and 1.4% in women. [1,2]
- RISK FACTORS
- Obesity or overweight - by far, the most important risk factor. OSA is present in up to 40% of people with a 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
- Hypothyroidism
- Acromegaly [1,2]
- SYMPTOMS
Symptoms of Moderate to Severe OSA | |
---|---|
Symptom | % of affected individuals |
Snoring | 90% |
Reported apnea | 80% |
Hypertension | 74% |
Nocturnal choking / gasping | 52% |
Excessive daytime fatigue | 50% |
Morning headache | 22% |
- PATHOPHYSIOLOGY
- OSA is marked by obstruction of the upper airways during sleep, which can occur through the following mechanisms:
- Fat deposition - fat deposition in the tongue and pharynx causes airway narrowing that increases the risk of collapse during sleep
- Craniofacial abnormalities - craniofacial abnormalities, including an elongated soft palate, shortened mandible, retro-positioned mandible, and inferior positioning of the hyoid bone, are associated with a higher risk of OSA
- Enlarged tonsils and/or adenoid tissue - enlargement of the tonsils and/or adenoid tissue may cause or worsen OSA, especially in children
- When the airway is obstructed, intermittent hypoxemia occurs, causing loss of synchronized movement between the thorax and abdomen (paradoxical breathing), activation of the sympathetic nervous system, and arousal. The cycle then repeats itself over and over again.
- 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]
- SCREENING
Screening Recommendation for OSA |
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USPSTF
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AASM
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- DIAGNOSIS
- OSA disease categories
- The table below gives the categories 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 definitions are somewhat arbitrary. The cutoff for severe OSA is based on cohort studies that showed an increased risk of hypertension for AHI values greater than 30. [5]
OSA Disease Categories | |
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AHI/REI | OSA severity |
5 - 14.9 | Mild |
15 - 29.9 | Moderate |
≥ 30 | Severe |
VA/DoD 2019 OSA Clinical Practice Guidelines |
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Whom to screen
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Initial testing
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Results
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Treatment
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- TREATMENT
- Overview
- In observational studies, OSA has been associated with a number of adverse cardiovascular outcomes, including cardiovascular disease, atrial fibrillation, stroke, and death. However, treating OSA with CPAP has not been shown to improve these outcomes in several large randomized controlled trials (see SAVE study and ISAACC study below). This suggests that OSA may be a marker of adverse cardiovascular risk as opposed to a causal factor.
- Daytime sleepiness has been shown to improve with CPAP, although, studies were unblinded and sleepiness is subjective. The effects of CPAP on blood pressure are modest, with average reductions of 0 - 3 mmHg in large trials.
- 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. [6]
- 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 therapy [4]
- Positive airway pressure (PAP)
- Overview - pressure from a mask covering the nose, mouth, or both creates a pneumatic splint that keeps the airways open during sleep. Types of PAP include continuous (CPAP), bilevel (BPAP), and autotitrating (APAP).
- Efficacy - PAP is the most studied and preferred treatment for OSA. When used appropriately, PAP reduces the AHI to the normal range in more than 90% of patients. Acceptable adherence is typically defined as at least 4 hours of use for ≥ 5 nights a week.
- Disadvantages - the main drawback to PAP is patient acceptance. In studies lasting up to 4 years, PAP adherence has ranged from 65 - 80%. Side effects of PAP include discomfort, upper airway dryness, nasal congestion, and skin irritation. [1,2,5,6]
- Mandibular advancement devices
- Overview - A mandibular advancement device, which covers the upper and lower teeth, holds the mandible in an advanced position, increasing upper airway volume
- Efficacy - mandibular advancement devices are not as effective as PAP and generally are not recommended for severe OSA. In a meta-analysis encompassing 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]
- Surgery
- Overview - surgery is typically recommended for nonobese patients with craniofacial abnormalities. The most common procedure is a uvulopalatopharyngoplasty (UPPP), where a portion of the uvula and soft palate are removed (UPPP illustration). Maxillomandibular advancement (MMA) is another more complex surgery that involves cutting and repositioning the mandible and maxilla (MMA illustration). Adenotonsillectomy may be indicated if the tonsils and adenoids are enlarged.
- 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] In another study, modified UPPP with minimally invasive tongue reduction was superior to medical management in reducing the AHI in patients with moderate-to-severe OSA who had failed conventional therapy (AHI difference at 6 months of 17.6 events). [PMID 32886102]
- 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 OSA patients (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 positively affect 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 symptom worsening 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 with 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 CNS depressants (e.g. insomnia medications, opiates, benzodiazepines) may worsen OSA and should be avoided if possible [1,2,5,6]
- Upper airway stimulation
- Overview - in May 2014, the FDA approved the Inspire® Upper Airway Stimulation (UAS) device, the first implantable treatment for OSA. The device is comprised of a pulse generator implanted subcutaneously below the right clavicle that is connected to a sensor in the fourth intercostal space and a lead stimulator that runs along the hypoglossal nerve beneath the chin. When the sensor detects a breath, it sends a signal to the pulse generator, which in turn, stimulates the hypoglossal nerve. Hypoglossal nerve stimulation moves the tongue forward, opening the airway during inspiration (see Inspire website for more).
- Efficacy and side effects - see the STAR study below
- eXciteOSA® tongue stimulator
- Overview - the eXciteOSA® tongue stimulator is a device placed in the mouth for 20 minutes a day while the patient is awake. The stimulator causes the tongue muscle to contract, strengthening it over time and increasing its resting tone; this helps hold the airway open at night. The device, which is controlled by a smartphone app, is used once daily for 6 weeks straight, after which use is reduced to twice weekly. Side effects during use include excessive salivation (14%), tongue discomfort (10%), tooth filling sensitivity (4%), metallic taste and gagging sensation (4.29%), and tightness in the jaw (1.43%). The FDA authorized marketing of the device in 2021 for snoring and mild OSA. eXciteOSA® device website
- Efficacy - A cohort study in 70 patients with sleep-disordered breathing found that it reduced average objective snoring time by 48%. In a subset of 38 patients with mild OSA, the average AHI was reduced from 9.8 to 4.7/hour, and the ODI declined from 7.8 to 4.3/hour. [PMID 33772397]
- STUDIES
- 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
Baseline characteristics
- 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
Results
Duration: Average of 3.7 years | |||
Outcome | CPAP | Usual care | Comparisons |
---|---|---|---|
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 |
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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
Baseline characteristics
- 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. CPAP machines were titrated before patient discharge.
Primary outcome: Composite of the first cardiovascular events (cardiovascular death or nonfatal events [acute myocardial infarction, nonfatal stroke, hospital admission for heart failure, and new hospitalizations for unstable angina or transient ischemic attack])
Results
Duration: Median of 3.35 years | |||
Outcome | CPAP | Usual care | Comparisons |
---|---|---|---|
Primary outcome | 16% | 17% | p=0.40 |
Overall mortality | 4% | 5% | p=0.44 |
CV death | 2% | 2% | p=0.64 |
Myocardial infarction | 6% | 6% | p=0.86 |
Stroke | 1% | <1% | p=0.42 |
A fib or other arrhythmia | 2% | 3% | p=0.56 |
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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
Baseline characteristics
- 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
Results
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.
- BIBLIOGRAPHY
- 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)
- 7 - PMID 27397659 - Quality Measure for Screening for Adult Obstructive Sleep Apnea by Primary Care Physicians, J Clin Sleep Med (2016)
- 8 - USPSTF website