Sleep Medicine

EFFICACY OF PAP THERAPY

The American Academy of Sleep Medicine practice guidelines for PAP are based on 342 articles, most rated as evidence levels I and II, concluding that CPAP is superior to conservative treatment to:

• Eliminate respiratory disturbances
• Reduce the apnea–hypopnea index
• Decrease the arousal index on electroencephalogram
• Increase in the total amount of slow-wave or N3 sleep
• Reduce daytime sleepiness.²

These practice parameters are based on evidence of improved daytime sleepiness and reduced incidence of cardiovascular events in patients with moderate to severe obstructive sleep apnea (OSA) treated with PAP. The evidence is less clear for neurocognitive markers and cardiovascular events in the treatment of patients with mild sleep apnea.

Sleepiness

A study evaluated sleepiness outcomes in 149 patients with severe sleep apnea with an average apnea–hypopnea index of 69 relative to the duration of nightly CPAP use. Sleepiness was measured using the Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale, and Multiple Sleep Latency Test. Results suggest that a greater percentage of patients had improved daytime sleepiness as the total hours of sleep using CPAP increased.³

The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, multicenter, randomized study of neurocognitive function in patients with OSA (N = 1,098).⁴ Subjective sleepiness as measured by the Epworth Sleepiness Scale showed statistically significant improvement at 2 and 6 months for patients with moderate to severe OSA using CPAP. Objective sleepiness as measured by the Maintenance of Wakefulness Test showed statistically significant improvement (ie, improved daytime alertness) at 2 and 6 months for patients with severe OSA using CPAP.

Neurocognitive function

APPLES also tested for attention and psycho­motor function as well as verbal learning and memory, though no statistically significant improvements were found in these parameters.⁴ Executive function and frontal lobe function showed transient improvement at 2 months in patients with severe sleep apnea using CPAP, but the improvement was not statistically significant at 6 months.

Cardiovascular outcomes

Hypertension and cardiovascular disease. Use of CPAP therapy reduces blood pressure in individuals with hypertension. A study of 32 patients who had a baseline polysomnography with 19 hours of continuous mean arterial blood pressure monitoring were treated with therapeutic CPAP (n = 16) or subtherapeutic CPAP (n = 16).⁵ Therapeutic treatment with CPAP for patients with moderate to severe OSA resulted in statistically significant reductions in mean arterial pressure for both systolic and diastolic pressures. The blood pressure reductions achieved are estimated to reduce coronary artery diseases by 37% and stroke by 56%.⁵

The risk of cardiovascular events in men with severe sleep apnea is high but mitigated by the use of CPAP. In a cohort of 1,651 men, untreated severe sleep apnea resulted in a threefold increase in the rate of cardiovascular events per 1,000 patient-years compared with 4 other groups: a control group, men who snore, men with untreated mild to moderate sleep apnea, and men with OSA using CPAP.⁶ However, when men with severe sleep apnea use CPAP, the risk of cardiovascular events is reduced to the rate in men who snore.

Atrial fibrillation. In patients with atrial fibrillation treated with direct-current cardioversion-
defibrillation, the recurrence of atrial fibrillation at 12 months was greater in patients with untreated OSA (82%) compared with a control group (53%) and patients treated for OSA (42%).⁷

Heart failure. In a study of 24 patients with heart failure, an ejection fraction less than 45%, and OSA, patients were randomized to a control group for medical treatment or medical treatment and nasal CPAP for 1 month.⁸ In the CPAP group, mean systolic blood pressure and heart rate were reduced, resulting in an improved ejection fraction compared with baseline, as well as compared with patients in the control group.

In patients with heart failure (N = 66) with and without Cheyne-Stokes respirations in central sleep apnea, patients treated with CPAP were found to have a 60% relative risk reduction in mortality-cardiac transplant rate compared with the control group not using CPAP.⁹ Further stratification in this study showed that patients with significant Cheyne-Stokes respirations and central sleep apnea had an improved ejection fraction at 3 months and an 81% reduced mortality-cardiac transplant rate.⁹

Adherence to PAP therapy is a problem in terms of both frequency of use and duration of use per night. A review of randomized control trials of CPAP compliance between 2011 and 2015 found adherence varied widely from 35% to 87%.¹⁰ The average hours of PAP use per night was found to be 5 hours in APPLES.⁴ Patients adherent to PAP therapy at 1 month remained adherent at 1 year, suggesting patients using CPAP for 1 month were more likely to continue use at 1 year.¹⁰ Impediments to PAP use typically involve the facial interface discomfort, lack of humidity, and pressure intolerance.

FEATURES OF PAP DEVICES

Today’s PAP devices have features designed to make them easier to use and more comfortable to improve adherence to therapy. Facial interface options, heated humidifiers, tubing accessories, cleaning devices, reporting of compliance data via telecommunication, and pressure adjustment features of PAP devices may improve patient adherence and comfort, as highlighted in the case scenarios presented below.

Interfaces

Case scenario #1

A 32-year-old woman with moderate sleep apnea complains that her PAP nasal mask is making very loud noises and is disturbing her bed partner. She is a side sleeper and also reports that she wakes with an extremely dry mouth.

Management of the leak could include which of the following?

1. Chin strap
2. Avoidance of facial creams before bedtime
3. CPAP pillow
4. Clean the mask daily
5. All of the above

Answer: All of the above.

There are many types of PAP interfaces such as nasal masks, nasal pillows, nasal cushions, full-face masks, and less frequently used oral and total face masks. The mask interface is a common impediment to use of PAP therapy often due to poor mask fit or leakage.

Nasal masks cover only the nose and require that the mouth remains closed, which can be achieved with the addition of a chin strap. Nasal masks are available in a variety of materials including cloth. Nasal pillows actually go into the nostrils whereas the nasal mask is positioned under the nose. A nasal cushion mask sits under the nose but does not go into the nostrils.

A study by Lanza and colleagues¹¹ evaluated patient comfort with PAP therapy based on the type of nasal interface mask. Patients using nasal pillows had improvement with respect to swollen eyes, discomfort, skin breakdown, and marks on the face compared with patients using nasal masks; however, nasal pillows can cause nostril pain.

Several types of full-face masks are available, some that fit over the bridge of the nose and some that fit just under the nose. A variety of head straps are available to secure full-face masks. One benefit of full-face masks is that air pressure is delivered to both the nose and the mouth, so the mouth can be open or closed. However, the larger surface area of the full-face mask increases the potential for leaks. A study of adherence in 20 patients using CPAP with nasal masks or full-face masks evaluated hours per use, adherence at 12 months, and comfort.¹² Patients using full-face masks had more hours per use, better adherence at 12 months, and more comfort than patients using nasal masks.

Interface skin irritation and leak management. To help combat skin irritation, particularly for patients with rosacea, cloth products are available for use beneath the mask and headgear. Silicone pads for masks that cause pressure on the bridge of the nose can help protect against skin breakdown. Sleeping positions other than the supine position can contribute to mask leak. CPAP pillows are designed to allow patients to sleep in their desired position while maintaining an adequate mask seal. The pillows are shaped or have cutouts that prevent the mask from pushing on the pillow and creating a leak.

Humidification

Case scenario #2

A 54-year-old man with severe sleep apnea recently initiated CPAP therapy. He quickly discontinued use due to nasal congestion.

Which of the following is NOT recommended?

1. Assure adequate heated humidification
2. Assure that the apnea is adequately treated
3. Use of a full-face mask
4. Use of short-acting nasal decongestants
5. Use of a topical nasal steroid

Answer: Use of short-acting nasal decongestants.

Nasal congestion is a common reason for nonadherence to CPAP therapy.¹³ Pressurized air is very drying and can be very uncomfortable. Residual apneic events can even precipitate further congestion. The use of humidification with CPAP can improve patient comfort and compliance. The vast majority of patients use CPAP devices with heated humidifiers. Heated humidification has been found to increase CPAP use and improve daytime sleepiness and feelings of satisfaction and being refreshed compared with cold humidity or no humidity.¹⁴ Cold humidification improved daytime sleepiness and satisfaction, but not to the degree found with heated humidification.

Heated humidifiers are incorporated in the CPAP machine or attach to it. Heated in-line tubing helps with “rain out,” which refers to water condensation inside the tubing and mask associated with CPAP humidification.

Topical decongestants can actually worsen congestion and cause a reflex vasodilation. Topical nasal steroids can be used for nasal congestion and may be beneficial.

The tubing from the PAP device to the facial interface can be a source of irritation to patients due to rubbing against the skin or entanglement. Products to cover the tubing to reduce irritation and avoid entanglement are available. Extra-long tubing is also available.

Cleaning

Some people find cleaning CPAP equipment daunting. Cleaning devices are available and recommended to patients looking for reassurance about how to keep their CPAP equipment clean. There are also CPAP wipes to clean the mask of oils and creams from the skin to improve the mask seal and reduce leaks.

Pressure control

Advanced modalities are available to adjust how pressure is delivered by PAP devices, including ramp, APAP, pressure relief, and BiPAP. Ramp is a feature that delivers a lower pressure at the beginning of the sleep cycle and slowly increases pressure to therapeutic levels. The lower pressure makes it easier for the user to fall asleep and builds to therapeutic pressure once asleep. APAP adjusts the pressure automatically when needed and reduces the pressure when not needed. Pressure relief is a feature that allows the PAP pressure to decrease at the point of expiration. BiPAP gives a distinct pressure on inspiration and a distinctively different and lower pressure at the point of expiration.

Auto-PAP

Case scenario #3

A 52-year-old woman with hypertension and mild sleep apnea has a polysomnogram with an apnea–hypopnea index of 7 events per hour that increase to 32 events per hour in rapid eye movement (REM) sleep. She is on CPAP at 5 cm of water, but complains of waking every 2 hours with a sense of panic and hot flashes.

Which of the following is the most likely cause of her symptoms?

1. An underlying anxiety disorder
2. An underlying heart condition
3. Perimenopausal symptoms
4. Undertreated REM-related apnea
5. None of the above

Answer: While all of these choices can occur, the most likely cause is undertreated REM-related apnea.

What would be the best next step in treatment for this patient?

1. Hormonal replacement therapy
2. Positional therapy in addition to CPAP
3. APAP
4. Anxiolytic medication
5. All of the above

Answer: APAP.

APAP incorporates an algorithm that detects and adjusts to airflow, pressure fluctuations, and airway resistance. The consensus from the American Academy of Sleep Medicine is that APAP is useful in the case of:

• Pressure intolerance
• REM apnea or positional apnea
• Inadequate in lab PAP titration
• Planned weight loss (bariatric surgery)
• Recurrent symptoms after long-term CPAP use.¹⁵

Pressure relief

Case scenario #4

A 45-year-old man with severe sleep apnea uses CPAP at 10 cm of water. He complains of the inability to exhale against the pressure from the device.

What would be the best next step?

1. Set the pressure relief to a maximum of 3
2. Lower the pressure of CPAP and check a download use at a lower pressure
3. BiPAP titration study in the laboratory
4. Switch to BiPAP if insurance allows
5. Change to a different mask

Answer: Set the pressure relief to a maximum of 3.

The CPAP device delivers pressure in conjunction with the patient’s inspiration and expiration. At the point of expiration, there is a decrease in the pressure delivered by the device to make it easier for the user to exhale. Three selectable settings provide flow-based pressure relief with a setting of 1 for the least degree of pressure reduction and a setting of 3 for the greatest degree of pressure reduction.¹⁶

In a study of the effect of PAP with pressure relief, 93 patients were assigned to use APAP without pressure relief, CPAP with pressure relief (C-Flex), or APAP with pressure relief (A-Flex).¹⁶ At 3 and 6 months, patients using A-Flex had the best adherence to therapy.

Quality of life was also examined in this same study.¹⁶ For patients using APAP alone, there was no statistically significant difference in the Epworth Sleepiness Scale measuring daytime sleepiness or the Pittsburgh Sleep Quality Index. However, in patients using A-Flex, daytime sleepiness improved, as did sleep quality, with statistically significant improvement at 3 months.

Bilevel PAP

Case scenario #5

A 62-year-old man with severe sleep apnea uses CPAP set at 17 cm of water and pressure relief set at 3. He stopped using CPAP due to abdominal pain, extreme belching, and pressure intolerance.

What would be the appropriate next step?

1. Use of simethicone
2. Elevate the head while using PAP therapy
3. BiPAP titration study in the laboratory
4. Switching directly to BiPAP if insurance allows
5. All of the above

Answer: All of the above.

BiPAP devices provide 2 distinct pressures, one for inhalation and one for exhalation. BiPAP also has the ability to deliver a higher overall pressure. A CPAP device typically has a maximum pressure of 20 cm of water, but BiPAP has a maximum pressure of 25 cm of water on inspiration. BiPAP may be helpful in patients with air aphasia and extreme belching. If a patient cannot tolerate CPAP because of the pressure, and if C-Flex has not alleviated the problem, BiPAP would be the next step.

The effectiveness and level of comfort of BiPAP compared with CPAP for the treatment of OSA was evaluated by the American Academy of Sleep Medicine.² The analysis of 7 randomized control trials reporting level I and II evidence found that BiPAP was as effective as CPAP in the treatment of OSA in patients with no comorbidities. For patients with OSA and comorbidities, a level III evidence study reported an increased level of comfort in patients using BiPAP.

Innovative strategies and approaches focusing on patient factors affecting PAP adherence include motivational interviewing, motivational enhancement, telemedicine, and desensitization techniques.

Motivational interviews and enhancement

Motivational interviewing and motivational enhancement were first used to help with alcohol abuse.¹⁷ Motivational interviewing is goal-oriented, patient-centered counseling to elicit a particular behavioral change. The goal is to explore and resolve ambivalence, increase engagement, and evoke a positive response and perspective that builds momentum and results in action.

Motivational enhancement and motivational engagement in the use of PAP therapy were evaluated in the Patient Engagement Study.¹⁸ Patients were assigned to usual care (n = 85,358) or active patient engagement (APE) (n = 42,679). Usual care involved diagnosis of apnea, initiation of CPAP, and follow-up, whereas APE included daily feedback (ie, daily scores of apnea–hypopnea index, mask leaks, hours used), positive praise messages, and personal coaching assistance. Overall adherence for patients assigned to APE was 87% compared with 70% in the usual-care group. The hours of use per night also increased for patients in the APE group.

The Best Apnea Interventions for Research trial randomized patients with or at risk of cardiovascular disease (N = 169) to CPAP alone or CPAP with motivational enhancements for 6 months.¹⁹ Motivational enhancements and interventions included brief in-person and phone interventions. An overall average difference of 99 minutes per night improvement in CPAP use was reported in the motivational enhancement group compared with CPAP alone.

The Motivational Interviewing Nurse Therapy study trained nurses in motivational interviewing and randomized 106 patients with newly diagnosed OSA to CPAP alone or CPAP plus motivational interviews.²⁰ Motivational interviews involved 3 sessions: 1 to build motivation prior to the CPAP titration, 1 to strengthen the commitment to achieve the prescribed time, and a booster session 1 month after CPAP setup. Adherence was found to improve at 1, 2, and 3 months in the motivational interview group; however, no difference between the 2 groups in adherence was noted at 12 months.

Telemedicine

The role of telemedicine in improving adherence with CPAP therapy was evaluated in 75 patients with moderate to severe apnea randomized to APAP alone or with phone call support from a research coordinator.²¹ Phone calls occurred 2 days after device setup, and daily monitoring of several factors was done via modem. Patients were contacted if the mask was leaking more than 30% of the night, use was less than 4 hours per night on 2 consecutive nights, the apnea–hypopnea index was greater than 10, or the average pressure needed was higher than 16 cm of water. Statistically significant improvement was found in the telemedicine group in mean adherence, minutes used per day, and mean amount of time spent with the patients.

Desensitization to PAP therapy

Case scenario #6

A 33-year-old woman with a history of anxiety and depression and a remote history of abuse as a child was diagnosed with severe apnea. When she tries to use her CPAP, she has a sense of panic and cannot proceed.

Which of the following has NOT been shown to be beneficial in this situation?

1. Psychologist for behavioral therapy
2. Desensitization protocol
3. PAP “NAP”
4. Short-acting hypnotics
5. None of the above

Answer: Short-acting hypnotics.

The short-acting hypnotic zaleplon (Sonata) was evaluated in a 1-month study of 88 patients compared with placebo control, and no difference was found between the 2 groups in measures of adherence to therapy or symptoms.²²

PAP NAP. For some people, at-home desensitization is not enough, and a sleep lab session may be needed. A PAP NAP is a daytime study conducted in the sleep lab. Patients do not necessarily sleep, but work with a technologist with a minimal hookup to polysomnography equipment on mask desensitization, as well as biofeedback techniques. PAP NAPs are indicated for patients with claustrophobia, anxiety surrounding PAP therapy, or pressure intolerance.

A study of 99 patients with moderate to severe apnea and insomnia and concomitant psychiatric disorders resistant to CPAP evaluated adherence in a group receiving a PAP NAP (n = 39) compared with a control group (n = 60).²³ The PAP NAP group had marked improvement in completion of CPAP titration in the lab, filling the CPAP prescription, and using CPAP more than 5 days a week and more than 4 hours a night.

A new innovative concept called the Sleep Apnea Patient-Centered Outcomes Network is a collaborative group that includes patients, researchers, and clinicians.²⁴ The group addresses issues such as cost, outcomes, and value in the diagnosis and treatment of sleep apnea. A patient-centered website provides forums, education, and data collection capability for researchers (myapnea.org).

SUMMARY

PAP therapy is the gold standard for treatment of patients with moderate to severe OSA, though poor adherence to PAP therapy is a persistent problem. Advanced features in PAP devices such as APAP and other innovative strategies like motivational enhancement and desensitization protocols and PAP NAP are being used to address poor adherence. More randomized controlled trials are needed to evaluate PAP for sleep apnea.

EFFICACY OF PAP THERAPY

The American Academy of Sleep Medicine practice guidelines for PAP are based on 342 articles, most rated as evidence levels I and II, concluding that CPAP is superior to conservative treatment to:

• Eliminate respiratory disturbances
• Reduce the apnea–hypopnea index
• Decrease the arousal index on electroencephalogram
• Increase in the total amount of slow-wave or N3 sleep
• Reduce daytime sleepiness.²

These practice parameters are based on evidence of improved daytime sleepiness and reduced incidence of cardiovascular events in patients with moderate to severe obstructive sleep apnea (OSA) treated with PAP. The evidence is less clear for neurocognitive markers and cardiovascular events in the treatment of patients with mild sleep apnea.

Sleepiness

A study evaluated sleepiness outcomes in 149 patients with severe sleep apnea with an average apnea–hypopnea index of 69 relative to the duration of nightly CPAP use. Sleepiness was measured using the Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale, and Multiple Sleep Latency Test. Results suggest that a greater percentage of patients had improved daytime sleepiness as the total hours of sleep using CPAP increased.³

The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, multicenter, randomized study of neurocognitive function in patients with OSA (N = 1,098).⁴ Subjective sleepiness as measured by the Epworth Sleepiness Scale showed statistically significant improvement at 2 and 6 months for patients with moderate to severe OSA using CPAP. Objective sleepiness as measured by the Maintenance of Wakefulness Test showed statistically significant improvement (ie, improved daytime alertness) at 2 and 6 months for patients with severe OSA using CPAP.

Neurocognitive function

APPLES also tested for attention and psycho­motor function as well as verbal learning and memory, though no statistically significant improvements were found in these parameters.⁴ Executive function and frontal lobe function showed transient improvement at 2 months in patients with severe sleep apnea using CPAP, but the improvement was not statistically significant at 6 months.

Cardiovascular outcomes

Hypertension and cardiovascular disease. Use of CPAP therapy reduces blood pressure in individuals with hypertension. A study of 32 patients who had a baseline polysomnography with 19 hours of continuous mean arterial blood pressure monitoring were treated with therapeutic CPAP (n = 16) or subtherapeutic CPAP (n = 16).⁵ Therapeutic treatment with CPAP for patients with moderate to severe OSA resulted in statistically significant reductions in mean arterial pressure for both systolic and diastolic pressures. The blood pressure reductions achieved are estimated to reduce coronary artery diseases by 37% and stroke by 56%.⁵

The risk of cardiovascular events in men with severe sleep apnea is high but mitigated by the use of CPAP. In a cohort of 1,651 men, untreated severe sleep apnea resulted in a threefold increase in the rate of cardiovascular events per 1,000 patient-years compared with 4 other groups: a control group, men who snore, men with untreated mild to moderate sleep apnea, and men with OSA using CPAP.⁶ However, when men with severe sleep apnea use CPAP, the risk of cardiovascular events is reduced to the rate in men who snore.

Atrial fibrillation. In patients with atrial fibrillation treated with direct-current cardioversion-
defibrillation, the recurrence of atrial fibrillation at 12 months was greater in patients with untreated OSA (82%) compared with a control group (53%) and patients treated for OSA (42%).⁷

Heart failure. In a study of 24 patients with heart failure, an ejection fraction less than 45%, and OSA, patients were randomized to a control group for medical treatment or medical treatment and nasal CPAP for 1 month.⁸ In the CPAP group, mean systolic blood pressure and heart rate were reduced, resulting in an improved ejection fraction compared with baseline, as well as compared with patients in the control group.

In patients with heart failure (N = 66) with and without Cheyne-Stokes respirations in central sleep apnea, patients treated with CPAP were found to have a 60% relative risk reduction in mortality-cardiac transplant rate compared with the control group not using CPAP.⁹ Further stratification in this study showed that patients with significant Cheyne-Stokes respirations and central sleep apnea had an improved ejection fraction at 3 months and an 81% reduced mortality-cardiac transplant rate.⁹

Adherence to PAP therapy is a problem in terms of both frequency of use and duration of use per night. A review of randomized control trials of CPAP compliance between 2011 and 2015 found adherence varied widely from 35% to 87%.¹⁰ The average hours of PAP use per night was found to be 5 hours in APPLES.⁴ Patients adherent to PAP therapy at 1 month remained adherent at 1 year, suggesting patients using CPAP for 1 month were more likely to continue use at 1 year.¹⁰ Impediments to PAP use typically involve the facial interface discomfort, lack of humidity, and pressure intolerance.

FEATURES OF PAP DEVICES

Today’s PAP devices have features designed to make them easier to use and more comfortable to improve adherence to therapy. Facial interface options, heated humidifiers, tubing accessories, cleaning devices, reporting of compliance data via telecommunication, and pressure adjustment features of PAP devices may improve patient adherence and comfort, as highlighted in the case scenarios presented below.

Interfaces

Case scenario #1

A 32-year-old woman with moderate sleep apnea complains that her PAP nasal mask is making very loud noises and is disturbing her bed partner. She is a side sleeper and also reports that she wakes with an extremely dry mouth.

Management of the leak could include which of the following?

1. Chin strap
2. Avoidance of facial creams before bedtime
3. CPAP pillow
4. Clean the mask daily
5. All of the above

Answer: All of the above.

There are many types of PAP interfaces such as nasal masks, nasal pillows, nasal cushions, full-face masks, and less frequently used oral and total face masks. The mask interface is a common impediment to use of PAP therapy often due to poor mask fit or leakage.

Nasal masks cover only the nose and require that the mouth remains closed, which can be achieved with the addition of a chin strap. Nasal masks are available in a variety of materials including cloth. Nasal pillows actually go into the nostrils whereas the nasal mask is positioned under the nose. A nasal cushion mask sits under the nose but does not go into the nostrils.

A study by Lanza and colleagues¹¹ evaluated patient comfort with PAP therapy based on the type of nasal interface mask. Patients using nasal pillows had improvement with respect to swollen eyes, discomfort, skin breakdown, and marks on the face compared with patients using nasal masks; however, nasal pillows can cause nostril pain.

Several types of full-face masks are available, some that fit over the bridge of the nose and some that fit just under the nose. A variety of head straps are available to secure full-face masks. One benefit of full-face masks is that air pressure is delivered to both the nose and the mouth, so the mouth can be open or closed. However, the larger surface area of the full-face mask increases the potential for leaks. A study of adherence in 20 patients using CPAP with nasal masks or full-face masks evaluated hours per use, adherence at 12 months, and comfort.¹² Patients using full-face masks had more hours per use, better adherence at 12 months, and more comfort than patients using nasal masks.

Interface skin irritation and leak management. To help combat skin irritation, particularly for patients with rosacea, cloth products are available for use beneath the mask and headgear. Silicone pads for masks that cause pressure on the bridge of the nose can help protect against skin breakdown. Sleeping positions other than the supine position can contribute to mask leak. CPAP pillows are designed to allow patients to sleep in their desired position while maintaining an adequate mask seal. The pillows are shaped or have cutouts that prevent the mask from pushing on the pillow and creating a leak.

Humidification

Case scenario #2

A 54-year-old man with severe sleep apnea recently initiated CPAP therapy. He quickly discontinued use due to nasal congestion.

Which of the following is NOT recommended?

1. Assure adequate heated humidification
2. Assure that the apnea is adequately treated
3. Use of a full-face mask
4. Use of short-acting nasal decongestants
5. Use of a topical nasal steroid

Answer: Use of short-acting nasal decongestants.

Nasal congestion is a common reason for nonadherence to CPAP therapy.¹³ Pressurized air is very drying and can be very uncomfortable. Residual apneic events can even precipitate further congestion. The use of humidification with CPAP can improve patient comfort and compliance. The vast majority of patients use CPAP devices with heated humidifiers. Heated humidification has been found to increase CPAP use and improve daytime sleepiness and feelings of satisfaction and being refreshed compared with cold humidity or no humidity.¹⁴ Cold humidification improved daytime sleepiness and satisfaction, but not to the degree found with heated humidification.

Heated humidifiers are incorporated in the CPAP machine or attach to it. Heated in-line tubing helps with “rain out,” which refers to water condensation inside the tubing and mask associated with CPAP humidification.

Topical decongestants can actually worsen congestion and cause a reflex vasodilation. Topical nasal steroids can be used for nasal congestion and may be beneficial.

The tubing from the PAP device to the facial interface can be a source of irritation to patients due to rubbing against the skin or entanglement. Products to cover the tubing to reduce irritation and avoid entanglement are available. Extra-long tubing is also available.

Cleaning

Some people find cleaning CPAP equipment daunting. Cleaning devices are available and recommended to patients looking for reassurance about how to keep their CPAP equipment clean. There are also CPAP wipes to clean the mask of oils and creams from the skin to improve the mask seal and reduce leaks.

Pressure control

Advanced modalities are available to adjust how pressure is delivered by PAP devices, including ramp, APAP, pressure relief, and BiPAP. Ramp is a feature that delivers a lower pressure at the beginning of the sleep cycle and slowly increases pressure to therapeutic levels. The lower pressure makes it easier for the user to fall asleep and builds to therapeutic pressure once asleep. APAP adjusts the pressure automatically when needed and reduces the pressure when not needed. Pressure relief is a feature that allows the PAP pressure to decrease at the point of expiration. BiPAP gives a distinct pressure on inspiration and a distinctively different and lower pressure at the point of expiration.

Auto-PAP

Case scenario #3

A 52-year-old woman with hypertension and mild sleep apnea has a polysomnogram with an apnea–hypopnea index of 7 events per hour that increase to 32 events per hour in rapid eye movement (REM) sleep. She is on CPAP at 5 cm of water, but complains of waking every 2 hours with a sense of panic and hot flashes.

Which of the following is the most likely cause of her symptoms?

1. An underlying anxiety disorder
2. An underlying heart condition
3. Perimenopausal symptoms
4. Undertreated REM-related apnea
5. None of the above

Answer: While all of these choices can occur, the most likely cause is undertreated REM-related apnea.

What would be the best next step in treatment for this patient?

1. Hormonal replacement therapy
2. Positional therapy in addition to CPAP
3. APAP
4. Anxiolytic medication
5. All of the above

Answer: APAP.

APAP incorporates an algorithm that detects and adjusts to airflow, pressure fluctuations, and airway resistance. The consensus from the American Academy of Sleep Medicine is that APAP is useful in the case of:

• Pressure intolerance
• REM apnea or positional apnea
• Inadequate in lab PAP titration
• Planned weight loss (bariatric surgery)
• Recurrent symptoms after long-term CPAP use.¹⁵

Pressure relief

Case scenario #4

A 45-year-old man with severe sleep apnea uses CPAP at 10 cm of water. He complains of the inability to exhale against the pressure from the device.

What would be the best next step?

1. Set the pressure relief to a maximum of 3
2. Lower the pressure of CPAP and check a download use at a lower pressure
3. BiPAP titration study in the laboratory
4. Switch to BiPAP if insurance allows
5. Change to a different mask

Answer: Set the pressure relief to a maximum of 3.

The CPAP device delivers pressure in conjunction with the patient’s inspiration and expiration. At the point of expiration, there is a decrease in the pressure delivered by the device to make it easier for the user to exhale. Three selectable settings provide flow-based pressure relief with a setting of 1 for the least degree of pressure reduction and a setting of 3 for the greatest degree of pressure reduction.¹⁶

In a study of the effect of PAP with pressure relief, 93 patients were assigned to use APAP without pressure relief, CPAP with pressure relief (C-Flex), or APAP with pressure relief (A-Flex).¹⁶ At 3 and 6 months, patients using A-Flex had the best adherence to therapy.

Quality of life was also examined in this same study.¹⁶ For patients using APAP alone, there was no statistically significant difference in the Epworth Sleepiness Scale measuring daytime sleepiness or the Pittsburgh Sleep Quality Index. However, in patients using A-Flex, daytime sleepiness improved, as did sleep quality, with statistically significant improvement at 3 months.

Bilevel PAP

Case scenario #5

A 62-year-old man with severe sleep apnea uses CPAP set at 17 cm of water and pressure relief set at 3. He stopped using CPAP due to abdominal pain, extreme belching, and pressure intolerance.

What would be the appropriate next step?

1. Use of simethicone
2. Elevate the head while using PAP therapy
3. BiPAP titration study in the laboratory
4. Switching directly to BiPAP if insurance allows
5. All of the above

Answer: All of the above.

BiPAP devices provide 2 distinct pressures, one for inhalation and one for exhalation. BiPAP also has the ability to deliver a higher overall pressure. A CPAP device typically has a maximum pressure of 20 cm of water, but BiPAP has a maximum pressure of 25 cm of water on inspiration. BiPAP may be helpful in patients with air aphasia and extreme belching. If a patient cannot tolerate CPAP because of the pressure, and if C-Flex has not alleviated the problem, BiPAP would be the next step.

The effectiveness and level of comfort of BiPAP compared with CPAP for the treatment of OSA was evaluated by the American Academy of Sleep Medicine.² The analysis of 7 randomized control trials reporting level I and II evidence found that BiPAP was as effective as CPAP in the treatment of OSA in patients with no comorbidities. For patients with OSA and comorbidities, a level III evidence study reported an increased level of comfort in patients using BiPAP.

Innovative strategies and approaches focusing on patient factors affecting PAP adherence include motivational interviewing, motivational enhancement, telemedicine, and desensitization techniques.

Motivational interviews and enhancement

Motivational interviewing and motivational enhancement were first used to help with alcohol abuse.¹⁷ Motivational interviewing is goal-oriented, patient-centered counseling to elicit a particular behavioral change. The goal is to explore and resolve ambivalence, increase engagement, and evoke a positive response and perspective that builds momentum and results in action.

Motivational enhancement and motivational engagement in the use of PAP therapy were evaluated in the Patient Engagement Study.¹⁸ Patients were assigned to usual care (n = 85,358) or active patient engagement (APE) (n = 42,679). Usual care involved diagnosis of apnea, initiation of CPAP, and follow-up, whereas APE included daily feedback (ie, daily scores of apnea–hypopnea index, mask leaks, hours used), positive praise messages, and personal coaching assistance. Overall adherence for patients assigned to APE was 87% compared with 70% in the usual-care group. The hours of use per night also increased for patients in the APE group.

The Best Apnea Interventions for Research trial randomized patients with or at risk of cardiovascular disease (N = 169) to CPAP alone or CPAP with motivational enhancements for 6 months.¹⁹ Motivational enhancements and interventions included brief in-person and phone interventions. An overall average difference of 99 minutes per night improvement in CPAP use was reported in the motivational enhancement group compared with CPAP alone.

The Motivational Interviewing Nurse Therapy study trained nurses in motivational interviewing and randomized 106 patients with newly diagnosed OSA to CPAP alone or CPAP plus motivational interviews.²⁰ Motivational interviews involved 3 sessions: 1 to build motivation prior to the CPAP titration, 1 to strengthen the commitment to achieve the prescribed time, and a booster session 1 month after CPAP setup. Adherence was found to improve at 1, 2, and 3 months in the motivational interview group; however, no difference between the 2 groups in adherence was noted at 12 months.

Telemedicine

The role of telemedicine in improving adherence with CPAP therapy was evaluated in 75 patients with moderate to severe apnea randomized to APAP alone or with phone call support from a research coordinator.²¹ Phone calls occurred 2 days after device setup, and daily monitoring of several factors was done via modem. Patients were contacted if the mask was leaking more than 30% of the night, use was less than 4 hours per night on 2 consecutive nights, the apnea–hypopnea index was greater than 10, or the average pressure needed was higher than 16 cm of water. Statistically significant improvement was found in the telemedicine group in mean adherence, minutes used per day, and mean amount of time spent with the patients.

Desensitization to PAP therapy

Case scenario #6

A 33-year-old woman with a history of anxiety and depression and a remote history of abuse as a child was diagnosed with severe apnea. When she tries to use her CPAP, she has a sense of panic and cannot proceed.

Which of the following has NOT been shown to be beneficial in this situation?

1. Psychologist for behavioral therapy
2. Desensitization protocol
3. PAP “NAP”
4. Short-acting hypnotics
5. None of the above

Answer: Short-acting hypnotics.

The short-acting hypnotic zaleplon (Sonata) was evaluated in a 1-month study of 88 patients compared with placebo control, and no difference was found between the 2 groups in measures of adherence to therapy or symptoms.²²

PAP NAP. For some people, at-home desensitization is not enough, and a sleep lab session may be needed. A PAP NAP is a daytime study conducted in the sleep lab. Patients do not necessarily sleep, but work with a technologist with a minimal hookup to polysomnography equipment on mask desensitization, as well as biofeedback techniques. PAP NAPs are indicated for patients with claustrophobia, anxiety surrounding PAP therapy, or pressure intolerance.

A study of 99 patients with moderate to severe apnea and insomnia and concomitant psychiatric disorders resistant to CPAP evaluated adherence in a group receiving a PAP NAP (n = 39) compared with a control group (n = 60).²³ The PAP NAP group had marked improvement in completion of CPAP titration in the lab, filling the CPAP prescription, and using CPAP more than 5 days a week and more than 4 hours a night.

A new innovative concept called the Sleep Apnea Patient-Centered Outcomes Network is a collaborative group that includes patients, researchers, and clinicians.²⁴ The group addresses issues such as cost, outcomes, and value in the diagnosis and treatment of sleep apnea. A patient-centered website provides forums, education, and data collection capability for researchers (myapnea.org).

SUMMARY

PAP therapy is the gold standard for treatment of patients with moderate to severe OSA, though poor adherence to PAP therapy is a persistent problem. Advanced features in PAP devices such as APAP and other innovative strategies like motivational enhancement and desensitization protocols and PAP NAP are being used to address poor adherence. More randomized controlled trials are needed to evaluate PAP for sleep apnea.

EFFICACY OF PAP THERAPY

The American Academy of Sleep Medicine practice guidelines for PAP are based on 342 articles, most rated as evidence levels I and II, concluding that CPAP is superior to conservative treatment to:

• Eliminate respiratory disturbances
• Reduce the apnea–hypopnea index
• Decrease the arousal index on electroencephalogram
• Increase in the total amount of slow-wave or N3 sleep
• Reduce daytime sleepiness.²

These practice parameters are based on evidence of improved daytime sleepiness and reduced incidence of cardiovascular events in patients with moderate to severe obstructive sleep apnea (OSA) treated with PAP. The evidence is less clear for neurocognitive markers and cardiovascular events in the treatment of patients with mild sleep apnea.

Sleepiness

A study evaluated sleepiness outcomes in 149 patients with severe sleep apnea with an average apnea–hypopnea index of 69 relative to the duration of nightly CPAP use. Sleepiness was measured using the Functional Outcomes of Sleep Questionnaire, Epworth Sleepiness Scale, and Multiple Sleep Latency Test. Results suggest that a greater percentage of patients had improved daytime sleepiness as the total hours of sleep using CPAP increased.³

The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, multicenter, randomized study of neurocognitive function in patients with OSA (N = 1,098).⁴ Subjective sleepiness as measured by the Epworth Sleepiness Scale showed statistically significant improvement at 2 and 6 months for patients with moderate to severe OSA using CPAP. Objective sleepiness as measured by the Maintenance of Wakefulness Test showed statistically significant improvement (ie, improved daytime alertness) at 2 and 6 months for patients with severe OSA using CPAP.

Neurocognitive function

APPLES also tested for attention and psycho­motor function as well as verbal learning and memory, though no statistically significant improvements were found in these parameters.⁴ Executive function and frontal lobe function showed transient improvement at 2 months in patients with severe sleep apnea using CPAP, but the improvement was not statistically significant at 6 months.

Cardiovascular outcomes

Hypertension and cardiovascular disease. Use of CPAP therapy reduces blood pressure in individuals with hypertension. A study of 32 patients who had a baseline polysomnography with 19 hours of continuous mean arterial blood pressure monitoring were treated with therapeutic CPAP (n = 16) or subtherapeutic CPAP (n = 16).⁵ Therapeutic treatment with CPAP for patients with moderate to severe OSA resulted in statistically significant reductions in mean arterial pressure for both systolic and diastolic pressures. The blood pressure reductions achieved are estimated to reduce coronary artery diseases by 37% and stroke by 56%.⁵

The risk of cardiovascular events in men with severe sleep apnea is high but mitigated by the use of CPAP. In a cohort of 1,651 men, untreated severe sleep apnea resulted in a threefold increase in the rate of cardiovascular events per 1,000 patient-years compared with 4 other groups: a control group, men who snore, men with untreated mild to moderate sleep apnea, and men with OSA using CPAP.⁶ However, when men with severe sleep apnea use CPAP, the risk of cardiovascular events is reduced to the rate in men who snore.

Atrial fibrillation. In patients with atrial fibrillation treated with direct-current cardioversion-
defibrillation, the recurrence of atrial fibrillation at 12 months was greater in patients with untreated OSA (82%) compared with a control group (53%) and patients treated for OSA (42%).⁷

Heart failure. In a study of 24 patients with heart failure, an ejection fraction less than 45%, and OSA, patients were randomized to a control group for medical treatment or medical treatment and nasal CPAP for 1 month.⁸ In the CPAP group, mean systolic blood pressure and heart rate were reduced, resulting in an improved ejection fraction compared with baseline, as well as compared with patients in the control group.

In patients with heart failure (N = 66) with and without Cheyne-Stokes respirations in central sleep apnea, patients treated with CPAP were found to have a 60% relative risk reduction in mortality-cardiac transplant rate compared with the control group not using CPAP.⁹ Further stratification in this study showed that patients with significant Cheyne-Stokes respirations and central sleep apnea had an improved ejection fraction at 3 months and an 81% reduced mortality-cardiac transplant rate.⁹

Adherence to PAP therapy is a problem in terms of both frequency of use and duration of use per night. A review of randomized control trials of CPAP compliance between 2011 and 2015 found adherence varied widely from 35% to 87%.¹⁰ The average hours of PAP use per night was found to be 5 hours in APPLES.⁴ Patients adherent to PAP therapy at 1 month remained adherent at 1 year, suggesting patients using CPAP for 1 month were more likely to continue use at 1 year.¹⁰ Impediments to PAP use typically involve the facial interface discomfort, lack of humidity, and pressure intolerance.

FEATURES OF PAP DEVICES

Today’s PAP devices have features designed to make them easier to use and more comfortable to improve adherence to therapy. Facial interface options, heated humidifiers, tubing accessories, cleaning devices, reporting of compliance data via telecommunication, and pressure adjustment features of PAP devices may improve patient adherence and comfort, as highlighted in the case scenarios presented below.

Interfaces

Case scenario #1

A 32-year-old woman with moderate sleep apnea complains that her PAP nasal mask is making very loud noises and is disturbing her bed partner. She is a side sleeper and also reports that she wakes with an extremely dry mouth.

Management of the leak could include which of the following?

1. Chin strap
2. Avoidance of facial creams before bedtime
3. CPAP pillow
4. Clean the mask daily
5. All of the above

Answer: All of the above.

There are many types of PAP interfaces such as nasal masks, nasal pillows, nasal cushions, full-face masks, and less frequently used oral and total face masks. The mask interface is a common impediment to use of PAP therapy often due to poor mask fit or leakage.

Nasal masks cover only the nose and require that the mouth remains closed, which can be achieved with the addition of a chin strap. Nasal masks are available in a variety of materials including cloth. Nasal pillows actually go into the nostrils whereas the nasal mask is positioned under the nose. A nasal cushion mask sits under the nose but does not go into the nostrils.

A study by Lanza and colleagues¹¹ evaluated patient comfort with PAP therapy based on the type of nasal interface mask. Patients using nasal pillows had improvement with respect to swollen eyes, discomfort, skin breakdown, and marks on the face compared with patients using nasal masks; however, nasal pillows can cause nostril pain.

Several types of full-face masks are available, some that fit over the bridge of the nose and some that fit just under the nose. A variety of head straps are available to secure full-face masks. One benefit of full-face masks is that air pressure is delivered to both the nose and the mouth, so the mouth can be open or closed. However, the larger surface area of the full-face mask increases the potential for leaks. A study of adherence in 20 patients using CPAP with nasal masks or full-face masks evaluated hours per use, adherence at 12 months, and comfort.¹² Patients using full-face masks had more hours per use, better adherence at 12 months, and more comfort than patients using nasal masks.

Interface skin irritation and leak management. To help combat skin irritation, particularly for patients with rosacea, cloth products are available for use beneath the mask and headgear. Silicone pads for masks that cause pressure on the bridge of the nose can help protect against skin breakdown. Sleeping positions other than the supine position can contribute to mask leak. CPAP pillows are designed to allow patients to sleep in their desired position while maintaining an adequate mask seal. The pillows are shaped or have cutouts that prevent the mask from pushing on the pillow and creating a leak.

Humidification

Case scenario #2

A 54-year-old man with severe sleep apnea recently initiated CPAP therapy. He quickly discontinued use due to nasal congestion.

Which of the following is NOT recommended?

1. Assure adequate heated humidification
2. Assure that the apnea is adequately treated
3. Use of a full-face mask
4. Use of short-acting nasal decongestants
5. Use of a topical nasal steroid

Answer: Use of short-acting nasal decongestants.

Nasal congestion is a common reason for nonadherence to CPAP therapy.¹³ Pressurized air is very drying and can be very uncomfortable. Residual apneic events can even precipitate further congestion. The use of humidification with CPAP can improve patient comfort and compliance. The vast majority of patients use CPAP devices with heated humidifiers. Heated humidification has been found to increase CPAP use and improve daytime sleepiness and feelings of satisfaction and being refreshed compared with cold humidity or no humidity.¹⁴ Cold humidification improved daytime sleepiness and satisfaction, but not to the degree found with heated humidification.

Heated humidifiers are incorporated in the CPAP machine or attach to it. Heated in-line tubing helps with “rain out,” which refers to water condensation inside the tubing and mask associated with CPAP humidification.

Topical decongestants can actually worsen congestion and cause a reflex vasodilation. Topical nasal steroids can be used for nasal congestion and may be beneficial.

The tubing from the PAP device to the facial interface can be a source of irritation to patients due to rubbing against the skin or entanglement. Products to cover the tubing to reduce irritation and avoid entanglement are available. Extra-long tubing is also available.

Cleaning

Some people find cleaning CPAP equipment daunting. Cleaning devices are available and recommended to patients looking for reassurance about how to keep their CPAP equipment clean. There are also CPAP wipes to clean the mask of oils and creams from the skin to improve the mask seal and reduce leaks.

Pressure control

Advanced modalities are available to adjust how pressure is delivered by PAP devices, including ramp, APAP, pressure relief, and BiPAP. Ramp is a feature that delivers a lower pressure at the beginning of the sleep cycle and slowly increases pressure to therapeutic levels. The lower pressure makes it easier for the user to fall asleep and builds to therapeutic pressure once asleep. APAP adjusts the pressure automatically when needed and reduces the pressure when not needed. Pressure relief is a feature that allows the PAP pressure to decrease at the point of expiration. BiPAP gives a distinct pressure on inspiration and a distinctively different and lower pressure at the point of expiration.

Auto-PAP

Case scenario #3

A 52-year-old woman with hypertension and mild sleep apnea has a polysomnogram with an apnea–hypopnea index of 7 events per hour that increase to 32 events per hour in rapid eye movement (REM) sleep. She is on CPAP at 5 cm of water, but complains of waking every 2 hours with a sense of panic and hot flashes.

Which of the following is the most likely cause of her symptoms?

1. An underlying anxiety disorder
2. An underlying heart condition
3. Perimenopausal symptoms
4. Undertreated REM-related apnea
5. None of the above

Answer: While all of these choices can occur, the most likely cause is undertreated REM-related apnea.

What would be the best next step in treatment for this patient?

1. Hormonal replacement therapy
2. Positional therapy in addition to CPAP
3. APAP
4. Anxiolytic medication
5. All of the above

Answer: APAP.

APAP incorporates an algorithm that detects and adjusts to airflow, pressure fluctuations, and airway resistance. The consensus from the American Academy of Sleep Medicine is that APAP is useful in the case of:

• Pressure intolerance
• REM apnea or positional apnea
• Inadequate in lab PAP titration
• Planned weight loss (bariatric surgery)
• Recurrent symptoms after long-term CPAP use.¹⁵

Pressure relief

Case scenario #4

A 45-year-old man with severe sleep apnea uses CPAP at 10 cm of water. He complains of the inability to exhale against the pressure from the device.

What would be the best next step?

1. Set the pressure relief to a maximum of 3
2. Lower the pressure of CPAP and check a download use at a lower pressure
3. BiPAP titration study in the laboratory
4. Switch to BiPAP if insurance allows
5. Change to a different mask

Answer: Set the pressure relief to a maximum of 3.

The CPAP device delivers pressure in conjunction with the patient’s inspiration and expiration. At the point of expiration, there is a decrease in the pressure delivered by the device to make it easier for the user to exhale. Three selectable settings provide flow-based pressure relief with a setting of 1 for the least degree of pressure reduction and a setting of 3 for the greatest degree of pressure reduction.¹⁶

In a study of the effect of PAP with pressure relief, 93 patients were assigned to use APAP without pressure relief, CPAP with pressure relief (C-Flex), or APAP with pressure relief (A-Flex).¹⁶ At 3 and 6 months, patients using A-Flex had the best adherence to therapy.

Quality of life was also examined in this same study.¹⁶ For patients using APAP alone, there was no statistically significant difference in the Epworth Sleepiness Scale measuring daytime sleepiness or the Pittsburgh Sleep Quality Index. However, in patients using A-Flex, daytime sleepiness improved, as did sleep quality, with statistically significant improvement at 3 months.

Bilevel PAP

Case scenario #5

A 62-year-old man with severe sleep apnea uses CPAP set at 17 cm of water and pressure relief set at 3. He stopped using CPAP due to abdominal pain, extreme belching, and pressure intolerance.

What would be the appropriate next step?

1. Use of simethicone
2. Elevate the head while using PAP therapy
3. BiPAP titration study in the laboratory
4. Switching directly to BiPAP if insurance allows
5. All of the above

Answer: All of the above.

BiPAP devices provide 2 distinct pressures, one for inhalation and one for exhalation. BiPAP also has the ability to deliver a higher overall pressure. A CPAP device typically has a maximum pressure of 20 cm of water, but BiPAP has a maximum pressure of 25 cm of water on inspiration. BiPAP may be helpful in patients with air aphasia and extreme belching. If a patient cannot tolerate CPAP because of the pressure, and if C-Flex has not alleviated the problem, BiPAP would be the next step.

The effectiveness and level of comfort of BiPAP compared with CPAP for the treatment of OSA was evaluated by the American Academy of Sleep Medicine.² The analysis of 7 randomized control trials reporting level I and II evidence found that BiPAP was as effective as CPAP in the treatment of OSA in patients with no comorbidities. For patients with OSA and comorbidities, a level III evidence study reported an increased level of comfort in patients using BiPAP.

Innovative strategies and approaches focusing on patient factors affecting PAP adherence include motivational interviewing, motivational enhancement, telemedicine, and desensitization techniques.

Motivational interviews and enhancement

Motivational interviewing and motivational enhancement were first used to help with alcohol abuse.¹⁷ Motivational interviewing is goal-oriented, patient-centered counseling to elicit a particular behavioral change. The goal is to explore and resolve ambivalence, increase engagement, and evoke a positive response and perspective that builds momentum and results in action.

Motivational enhancement and motivational engagement in the use of PAP therapy were evaluated in the Patient Engagement Study.¹⁸ Patients were assigned to usual care (n = 85,358) or active patient engagement (APE) (n = 42,679). Usual care involved diagnosis of apnea, initiation of CPAP, and follow-up, whereas APE included daily feedback (ie, daily scores of apnea–hypopnea index, mask leaks, hours used), positive praise messages, and personal coaching assistance. Overall adherence for patients assigned to APE was 87% compared with 70% in the usual-care group. The hours of use per night also increased for patients in the APE group.

The Best Apnea Interventions for Research trial randomized patients with or at risk of cardiovascular disease (N = 169) to CPAP alone or CPAP with motivational enhancements for 6 months.¹⁹ Motivational enhancements and interventions included brief in-person and phone interventions. An overall average difference of 99 minutes per night improvement in CPAP use was reported in the motivational enhancement group compared with CPAP alone.

The Motivational Interviewing Nurse Therapy study trained nurses in motivational interviewing and randomized 106 patients with newly diagnosed OSA to CPAP alone or CPAP plus motivational interviews.²⁰ Motivational interviews involved 3 sessions: 1 to build motivation prior to the CPAP titration, 1 to strengthen the commitment to achieve the prescribed time, and a booster session 1 month after CPAP setup. Adherence was found to improve at 1, 2, and 3 months in the motivational interview group; however, no difference between the 2 groups in adherence was noted at 12 months.

Telemedicine

The role of telemedicine in improving adherence with CPAP therapy was evaluated in 75 patients with moderate to severe apnea randomized to APAP alone or with phone call support from a research coordinator.²¹ Phone calls occurred 2 days after device setup, and daily monitoring of several factors was done via modem. Patients were contacted if the mask was leaking more than 30% of the night, use was less than 4 hours per night on 2 consecutive nights, the apnea–hypopnea index was greater than 10, or the average pressure needed was higher than 16 cm of water. Statistically significant improvement was found in the telemedicine group in mean adherence, minutes used per day, and mean amount of time spent with the patients.

Desensitization to PAP therapy

Case scenario #6

A 33-year-old woman with a history of anxiety and depression and a remote history of abuse as a child was diagnosed with severe apnea. When she tries to use her CPAP, she has a sense of panic and cannot proceed.

Which of the following has NOT been shown to be beneficial in this situation?

1. Psychologist for behavioral therapy
2. Desensitization protocol
3. PAP “NAP”
4. Short-acting hypnotics
5. None of the above

Answer: Short-acting hypnotics.

The short-acting hypnotic zaleplon (Sonata) was evaluated in a 1-month study of 88 patients compared with placebo control, and no difference was found between the 2 groups in measures of adherence to therapy or symptoms.²²

PAP NAP. For some people, at-home desensitization is not enough, and a sleep lab session may be needed. A PAP NAP is a daytime study conducted in the sleep lab. Patients do not necessarily sleep, but work with a technologist with a minimal hookup to polysomnography equipment on mask desensitization, as well as biofeedback techniques. PAP NAPs are indicated for patients with claustrophobia, anxiety surrounding PAP therapy, or pressure intolerance.

A study of 99 patients with moderate to severe apnea and insomnia and concomitant psychiatric disorders resistant to CPAP evaluated adherence in a group receiving a PAP NAP (n = 39) compared with a control group (n = 60).²³ The PAP NAP group had marked improvement in completion of CPAP titration in the lab, filling the CPAP prescription, and using CPAP more than 5 days a week and more than 4 hours a night.

A new innovative concept called the Sleep Apnea Patient-Centered Outcomes Network is a collaborative group that includes patients, researchers, and clinicians.²⁴ The group addresses issues such as cost, outcomes, and value in the diagnosis and treatment of sleep apnea. A patient-centered website provides forums, education, and data collection capability for researchers (myapnea.org).

SUMMARY

PAP therapy is the gold standard for treatment of patients with moderate to severe OSA, though poor adherence to PAP therapy is a persistent problem. Advanced features in PAP devices such as APAP and other innovative strategies like motivational enhancement and desensitization protocols and PAP NAP are being used to address poor adherence. More randomized controlled trials are needed to evaluate PAP for sleep apnea.

The most widely used treatment for patients with obstructive sleep apnea (OSA) is positive airway pressure (PAP) therapy. Improved quality of life and cardiovascular outcomes for patients with OSA using PAP have been demonstrated. However, for some patients with OSA, PAP therapy is difficult to use or tolerate. Fortunately, there are other available treatment interventions for patients with OSA such as lifestyle interventions, surgical interventions, hypoglossal nerve stimulation (HNS), oral appliance therapy (OAT), and expiratory PAP (EPAP) devices. These alternative treatments can also improve symptoms of OSA though data regarding cardiovascular outcomes are lacking.

LIFESTYLE INTERVENTIONS

Weight loss

Because a higher body mass index (BMI) increases the risk for OSA, weight loss should be recommended for patients with OSA who are overweight. Much of the research evaluating the effect of weight loss on OSA has methodologic limitations such as lack of randomization or controls, potential confounding variables, and limited follow-up. A randomized controlled trial of 72 overweight patients with mild OSA (apnea–hypopnea index [AHI] of 5 to 15) compared a group assigned to a very low calorie diet and lifestyle counseling with a control group.¹ At 1 year, weight loss of 15 kg or more resulted in a statistically significant reduction in their AHI to normal, resolving their OSA. A 15 kg weight loss in this study was associated with an overall reduction in the AHI of at least 2 units.

Exercise

Exercise is also recommended for patients with OSA, and it can lessen the severity of symptoms even without weight loss. A meta-analysis of 5 randomized trials of 129 patients reported a reduction in the AHI of as much as 6 events per hour in individuals assigned to a strict exercise regimen.² The reduction in the AHI occurred despite a slight reduction in BMI (1.37 kg/m²).

Sleep position

For some patients, sleeping in the supine position may worsen their OSA, in which case avoiding the supine sleep position is recommended. A sleep study such as polysomnography should be performed to confirm the resolution of OSA in the nonsupine position.³ Products such as pillows or vibratory feedback devices can help the patient avoid sleeping on the back. The ability to monitor patient adherence to sleep position therapy alone is very limited.

Alcohol avoidance

Alcohol consumption depresses the central nervous system, promotes waking, and increases daytime sleepiness, thus exacerbating OSA. Patients with untreated OSA should avoid alcohol because it worsens the duration and frequency of obstructive respiratory events during sleep, and it can worsen the degree of oxygen desaturation that occurs during abnormal respiratory events.⁴

Concomitant medications

A review of medications in patients with OSA is warranted. Use of benzodiazepines, benzodiazepine-receptor agonists, barbiturates, and opiates in patients with OSA should be avoided especially if OSA is untreated. If these medications are necessary, careful monitoring is recommended. Medications that can cause weight gain such as some antidepressants should also be avoided.

SURGICAL INTERVENTIONS

Surgical interventions for OSA target the location of the obstruction in the upper airway. The upper airway consists of 3 regions: the palate, oropharynx, and larynx.⁵ More than 30 surgical soft-tissue and skeletal interventions for OSA are reported in the literature.⁶

Evaluating the outcomes of various surgical interventions for OSA is hindered by differences in the definition of surgical success or cure. As such, surgical interventions for OSA remain controversial. The practice parameters from 2010 reviewed surgical modifications of the upper airway for adults with OSA.^7,8 Success is defined as a greater than 50% reduction in the AHI to fewer than 20 events per hour, whereas surgical cure is defined as a reduction in the AHI to fewer than 5 events per hour.⁷

Uvulopalatopharyngoplasty

Uvulopalatopharyngoplasty (UPPP) is a surgical procedure that remodels the throat via removal of the tonsils and the posterior surface of the soft palate and uvula and closure of the tonsillar pillars, and thus addresses retropalatal collapse. UPPP rarely achieves a surgical cure (ie, AHI < 5) and has been shown to have a 33% reduction in the AHI, with a postoperative average AHI remaining elevated at 29.⁸ (ie, moderate to severe OSA).8 In general, 50% of patients have a 50% reduction in AHI.⁹ The 4-year responder rate for UPPP is 44% to 50%.¹⁰ Factors limiting the long-term success of this procedure include weight gain, assessment of surgical candidates,¹¹ and decreased adherence to PAP therapy after the procedure.

The use of UPPP in combination with other surgical procedures has also been evaluated.⁸ The AHI in patients with OSA improved postoperatively when UPPP was done simultaneously or in a multiphase approach with radiofrequency ablation, midline glossectomy, tongue advancement, hyoid suspension, or maxillomandibular advancement, though greater improvement was noted with the multiphase approach.

Maxillomandibular advancement

Maxillomandibular advancement is a surgical procedure that moves the maxilla and mandible forward and expands the facial skeletal framework via LeFort I maxillary and sagittal split mandibular osteotomies. Maxillomandibular advancement achieves enlargement of the nasopharyngeal, retropalatal, and hypopharyngeal airway. This increases tension on the pharyngeal soft tissue, which enlarges the medial-lateral and anteroposterior dimensions of the upper airway.¹⁴

A meta-analysis of 45 studies evaluated the change in the AHI after maxillomandibular advancement in 518 patients.¹⁵ Secondary outcomes were surgical success (> 50% reduction in AHI to < 20 events per hour) and surgical cure (AHI < 5). Patients with a higher preoperative AHI achieved the greatest magnitude reduction in AHI but were less likely to achieve surgical success or cure. Patients with a lower preoperative AHI had a greater likelihood of surgical success and cure.

Bariatric surgery

Bariatric surgery is increasingly used for treatment of OSA in individuals with morbid obesity. A systematic review of bariatric surgery including the roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and biliopancreatic diversion evaluated 69 studies with 13,900 patients with OSA.¹⁶ OSA was found to be improved or eliminated in 75% of patients for all bariatric surgery procedures.

Used with permission from Inspire Medical Systems, Inc.

Indications and contraindications

The indications and contraindications for HNS are shown in Table 2.

Efficacy and outcomes

Stimulation of the hypoglossal nerve results in a multilevel mechanism of action: activation and protrusion of the tongue opens the oropharyngeal airway directly but also affects the retropalatal airway by a palatoglossal coupling action.¹⁹ Sleep lab testing with polysomnography is used to titrate the voltage of HNS to achieve an open airway that resolves apneic events and normalizes airflow, breathing patterns, and oxygen saturation levels.

Approval of HNS for OSA by the US Food and Drug Administration was based on findings in the Stimulation Therapy for Apnea Reduction (STAR) trial,¹⁷ a prospective trial of 126 patients at 22 centers in the United States and Europe with the primary outcomes of AHI and oxygen desaturation index. Secondary outcomes included quality of life as measured by the Functional Outcomes of Sleep Questionnaire and Epworth Sleepiness Scale (ESS). Patient demographics included mean age 54.5, 83% men, mean BMI of 28 kg/m², and mean baseline AHI of 34 (ie, severe OSA).

Data at 5 years for 97 of the 126 patients on HNS in the STAR trial is available.²⁰ The AHI was reduced an average of 70% to levels in the mild OSA range.^20,21 Overall, 85% of the patients had improved quality-of-life measures after HNS implantation, with increased Functional Outcomes of Sleep Questionnaire scores and ESS scores in the normal range over time. Consistent HNS therapy demonstrated sustained benefits at 5 years. The AHI improved by 50% or to less than 20 in 75% of patients, with 44% having resolved OSA and 78% improved to mild OSA (AHI < 15). Device-related adverse events occurred in 6% (9 of 126) of patients requiring replacement or repositioning of the stimulator or leads.²⁰

Moderate to severe snoring was prevalent at baseline in the STAR trial, but over the course of 5 years, 85% of bed partners of patients on HNS reported no or soft snoring.^17,21 Nightly use averaged 80% over 60 months based on patient reporting, with 87% reporting use at least 5 nights per week at 36 weeks.²⁰

In terms of predictors of response to HNS therapy, the oxygen desaturation index is the only characteristic that reached a level of statistical significance; patients with higher levels of oxygen desaturation tended to improve and tolerate therapy better long-term.²⁰ A randomized controlled trial of withdrawal of HNS therapy demonstrated increased AHI and oxygen desaturation index when therapy was withdrawn, followed by improvement when therapy resumed.²²

A clinical trial of 20 patients implanted with HNS after its approval in 2014 reported that the mean AHI decreased from 33 before implant to 5.1 after implant.²³ The ESS also improved from 10.3 before implant to 6 after implant. Mean adherence to device use was 7 (± 2) hours per night. The average stimulation amplitude was 1.89 (± 0.5) volts after the titration sleep study was completed. Similar reductions in AHI were reported by Huntley et al²⁴ for patients receiving HNS implant at 2 academic centers, with no differences between the 2 cohorts in postoperative AHI.

Adverse events

The adverse events reported with HNS are related to the implant procedure or the device.²¹ Procedure-related adverse events are incision discomfort, temporary tongue weakness, headache, and mild infection of incisions. The most common device-related adverse event is discomfort from the electrical stimulation. Tongue abrasion can also occur if the tongue protrudes and rubs against a sharp tooth. Dry mouth is also commonly reported.

HNS compared with UPPP

Outcomes in patients with moderate to severe OSA matched for BMI, demographics, and preoperative AHI were evaluated comparing patients undergoing HNS (n = 20) with patients receiving UPPP (n = 20).²⁵ The AHI decreased 29% postoperatively in patients with UPPP compared with 88% in patients with HNS, 65% of which had normalization of their AHI. Surgical success was achieved in 40% of patients in the UPPP group compared with 100% in the HNS group. Greater improvement in daytime sleepiness was noted in patients in the HNS group compared with the UPPP group.

OAT devices help protrude the mandible forward and stabilize it to maintain a more patent airway during sleep. Oral appliances can be custom-made or prefabricated. Oral appliances can be titratable or nontitratable: titration provides a mechanism to adjust mandibular protrusion analogous to PAP titration, whereas the absence of titration holds the mandible in a single position. The most effective oral appliances are custom-made and titratable.

Types of OAT devices

Custom oral appliances. Custom oral appliances are fabricated using digital or physical impressions of the patient’s oral structures. Custom oral appliances are made of biocompatible materials and engage both the maxillary and mandibular arches.

Custom oral appliances are made by a qualified dentist who takes maxillary and mandibular impressions with a bite registration using the George Gauge with 40% to 50% of maximum protrusion. The appliance is fabricated in a laboratory and then fitted to the patient, who is instructed to titrate the device 0.5 mm to 1 mm per week and follow-up with the dentist at 2-week intervals. Once the patient has titrated the device to the point of comfort or improved sleep quality or snoring, polysomnography should be done with the device in place and titrated to improve the AHI as much as possible. Follow-up is recommended at 6 months and annually thereafter.

Prefabricated oral appliances. Prefabricated oral appliances are of the boil-and-bite type, only partially modified to the patient’s oral structures.

Tongue-retaining devices. Another type of oral appliance is a tongue-retaining device, which is designed to hold the tongue forward and can be custom-made or prefabricated.

Patient considerations for OAT

Practice recommendations

• Prescribed OAT should be done by a qualified dentist, and a custom, titratable appliance is preferred
• OAT is preferred over no therapy for adults with OSA who are intolerant to PAP or prefer alternative therapies
• A qualified dentist should provide oversight for dental-related side effects or occlusal changes
• Follow-up sleep testing should be conducted to confirm efficacy or titrate treatment
• Periodic office visits with the sleep physician and qualified dentist are recommended.²⁶

The quality of evidence for these recommendations is low, with the exception of use of OAT rather than no therapy, which is considered of moderate quality.

Effects of OAT

Anatomic and physiologic effects. With OAT in place in the mouth, the airway caliber in the lateral dimension are increased, and the airway size at the retropalatal level is increased.^27–30 With respect to the tongue, increased genioglossus muscle activity has been reported with OAT.

Side effects. Side effects of OAT include excess salivation, dry mouth, tooth tenderness, soft-tissue changes, jaw discomfort, tooth movement, and occlusal changes such as difficulty chewing in the morning. Feelings of suffocation, vivid dreams, and anxiety have also been reported with OAT.^31–33

Efficacy and outcomes

Review of the data on the efficacy of OAT did not illuminate factors that predict treatment success.²⁶ Data indicate that in patients with mild OSA using OAT or PAP therapy, there was no significant difference in the percentage achieving their target AHI; however, patients with moderate to severe OSA had a statistically significant greater odds of achieving their target AHI using PAP therapy compared with OAT. Therefore, OAT should be reserved for patients with severe OSA who cannot use or are intolerant to PAP.

Moderate-grade quality of evidence was reviewed for the established OAT practice recommendations for OSA outcomes before and after use of custom, titratable OAT devices.²⁶ Use of a custom OAT device reduced the mean AHI, increased mean oxygen saturation, decreased the mean oxygen desaturation, decreased the arousal index, decreased the ESS, and increased quality of life compared with values prior to use of OAT.

With respect to adherence and discontinuation, patients using OAT had higher mean adherence and lower discontinuation because of side effects compared with patients using continuous PAP.²⁶

Nasal EPAP is a new treatment for OSA that consists of a mechanical valve worn in each naris at night. The valves have a low inspiratory resistance and a high expiratory resistance thus increased pressure occurs at exhalation.

Pressure at exhalation may counter the airway collapse in OSA. With the mouth closed and use of the nasal valves, the positive pressure during the normal respiratory cycle is utilized to maintain an open airway.³⁴ At the onset and throughout inspiration, the activity of the airway dilator muscles increases. At maximum expiration, right before the end of the expiratory pause, the dilator muscle stops abruptly and the airway is of its smallest caliber. The presence of the nasal valve at this point is thought to act as a pneumatic splint to the airway, and the nasal EPAP helps keep the airway patent during the next inspiratory phase.

Nasal EPAP valves are available in a 30-day starter kit. Intended for single-night use, the kit includes valves of increasing levels of expiration resistance: low (nights 1 and 2), medium (nights 3 and 4), and normal (nights 5–30).

Outcomes of nasal EPAP therapy

A multicenter 30-day in-home trial evaluated efficacy and compliance of nasal EPAP therapy.³⁵ The AHI was reduced by 50% or more in 14 of 34 (41%) patients using nasal EPAP compared with the control group at the 30-day follow-up. The patient-reported compliance with nasal EPAP was 94%. Patients in this study had mild to moderate OSA and did not have obesity or other comorbidities such as pulmonary hypertension or cardiovascular disease.

A randomized controlled trial compared nasal EPAP with a sham device in patients with newly diagnosed or untreated OSA (N = 250) for 3 months.³⁶ A median reduction of 52% in the AHI was noted in the intention-to-treat group (N = 229) during rapid eye movement (REM) and non-REM sleep, though it was statistically significant only during REM sleep and supine sleep. At 3 months, improved OSA was maintained in 42% of the patients using nasal EPAP compared with 10% of patients using a sham device. Improvements in daytime sleepiness and adherence with 88% using EPAP the entire night were also noted.

In a 12-month study of nasal EPAP, 67% of patients (34 of 51) used nasal EPAP for the full trial duration.³⁷ Of patients using nasal EPAP for 12 months, the median AHI was reduced by 71%, the ESS improved, and adherence to full-night use was 89%.

Patient considerations for nasal EPAP

In clinical practice, nasal EPAP therapy requires nasal patency and use of a chin strap in patients with mouth leakage. Nasal EPAP may be recommended for patients who travel frequently and can go without continuous PAP or bilevel PAP for short periods of time, and for patients who do not have significant medical comorbidities.

Side effects and limitations of nasal EPAP

Reported side effects of nasal EPAP include difficulty with exhalation, nasal discomfort, dry mouth, and headache. Nasal EPAP therapy is of limited use in patients with severe OSA and severe oxygen desaturation. The efficacy of nasal EPAP beyond 12 months is unknown. Use of nasal EPAP in patients with prior upper-airway surgery and in combination with other therapies is yet to be evaluated.

The most widely used treatment for patients with obstructive sleep apnea (OSA) is positive airway pressure (PAP) therapy. Improved quality of life and cardiovascular outcomes for patients with OSA using PAP have been demonstrated. However, for some patients with OSA, PAP therapy is difficult to use or tolerate. Fortunately, there are other available treatment interventions for patients with OSA such as lifestyle interventions, surgical interventions, hypoglossal nerve stimulation (HNS), oral appliance therapy (OAT), and expiratory PAP (EPAP) devices. These alternative treatments can also improve symptoms of OSA though data regarding cardiovascular outcomes are lacking.

LIFESTYLE INTERVENTIONS

Weight loss

Because a higher body mass index (BMI) increases the risk for OSA, weight loss should be recommended for patients with OSA who are overweight. Much of the research evaluating the effect of weight loss on OSA has methodologic limitations such as lack of randomization or controls, potential confounding variables, and limited follow-up. A randomized controlled trial of 72 overweight patients with mild OSA (apnea–hypopnea index [AHI] of 5 to 15) compared a group assigned to a very low calorie diet and lifestyle counseling with a control group.¹ At 1 year, weight loss of 15 kg or more resulted in a statistically significant reduction in their AHI to normal, resolving their OSA. A 15 kg weight loss in this study was associated with an overall reduction in the AHI of at least 2 units.

Exercise

Exercise is also recommended for patients with OSA, and it can lessen the severity of symptoms even without weight loss. A meta-analysis of 5 randomized trials of 129 patients reported a reduction in the AHI of as much as 6 events per hour in individuals assigned to a strict exercise regimen.² The reduction in the AHI occurred despite a slight reduction in BMI (1.37 kg/m²).

Sleep position

For some patients, sleeping in the supine position may worsen their OSA, in which case avoiding the supine sleep position is recommended. A sleep study such as polysomnography should be performed to confirm the resolution of OSA in the nonsupine position.³ Products such as pillows or vibratory feedback devices can help the patient avoid sleeping on the back. The ability to monitor patient adherence to sleep position therapy alone is very limited.

Alcohol avoidance

Alcohol consumption depresses the central nervous system, promotes waking, and increases daytime sleepiness, thus exacerbating OSA. Patients with untreated OSA should avoid alcohol because it worsens the duration and frequency of obstructive respiratory events during sleep, and it can worsen the degree of oxygen desaturation that occurs during abnormal respiratory events.⁴

Concomitant medications

A review of medications in patients with OSA is warranted. Use of benzodiazepines, benzodiazepine-receptor agonists, barbiturates, and opiates in patients with OSA should be avoided especially if OSA is untreated. If these medications are necessary, careful monitoring is recommended. Medications that can cause weight gain such as some antidepressants should also be avoided.

SURGICAL INTERVENTIONS

Surgical interventions for OSA target the location of the obstruction in the upper airway. The upper airway consists of 3 regions: the palate, oropharynx, and larynx.⁵ More than 30 surgical soft-tissue and skeletal interventions for OSA are reported in the literature.⁶

Evaluating the outcomes of various surgical interventions for OSA is hindered by differences in the definition of surgical success or cure. As such, surgical interventions for OSA remain controversial. The practice parameters from 2010 reviewed surgical modifications of the upper airway for adults with OSA.^7,8 Success is defined as a greater than 50% reduction in the AHI to fewer than 20 events per hour, whereas surgical cure is defined as a reduction in the AHI to fewer than 5 events per hour.⁷

Uvulopalatopharyngoplasty

Uvulopalatopharyngoplasty (UPPP) is a surgical procedure that remodels the throat via removal of the tonsils and the posterior surface of the soft palate and uvula and closure of the tonsillar pillars, and thus addresses retropalatal collapse. UPPP rarely achieves a surgical cure (ie, AHI < 5) and has been shown to have a 33% reduction in the AHI, with a postoperative average AHI remaining elevated at 29.⁸ (ie, moderate to severe OSA).8 In general, 50% of patients have a 50% reduction in AHI.⁹ The 4-year responder rate for UPPP is 44% to 50%.¹⁰ Factors limiting the long-term success of this procedure include weight gain, assessment of surgical candidates,¹¹ and decreased adherence to PAP therapy after the procedure.

The use of UPPP in combination with other surgical procedures has also been evaluated.⁸ The AHI in patients with OSA improved postoperatively when UPPP was done simultaneously or in a multiphase approach with radiofrequency ablation, midline glossectomy, tongue advancement, hyoid suspension, or maxillomandibular advancement, though greater improvement was noted with the multiphase approach.

Maxillomandibular advancement

Maxillomandibular advancement is a surgical procedure that moves the maxilla and mandible forward and expands the facial skeletal framework via LeFort I maxillary and sagittal split mandibular osteotomies. Maxillomandibular advancement achieves enlargement of the nasopharyngeal, retropalatal, and hypopharyngeal airway. This increases tension on the pharyngeal soft tissue, which enlarges the medial-lateral and anteroposterior dimensions of the upper airway.¹⁴

A meta-analysis of 45 studies evaluated the change in the AHI after maxillomandibular advancement in 518 patients.¹⁵ Secondary outcomes were surgical success (> 50% reduction in AHI to < 20 events per hour) and surgical cure (AHI < 5). Patients with a higher preoperative AHI achieved the greatest magnitude reduction in AHI but were less likely to achieve surgical success or cure. Patients with a lower preoperative AHI had a greater likelihood of surgical success and cure.

Bariatric surgery

Bariatric surgery is increasingly used for treatment of OSA in individuals with morbid obesity. A systematic review of bariatric surgery including the roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and biliopancreatic diversion evaluated 69 studies with 13,900 patients with OSA.¹⁶ OSA was found to be improved or eliminated in 75% of patients for all bariatric surgery procedures.

Used with permission from Inspire Medical Systems, Inc.

Indications and contraindications

The indications and contraindications for HNS are shown in Table 2.

Efficacy and outcomes

Stimulation of the hypoglossal nerve results in a multilevel mechanism of action: activation and protrusion of the tongue opens the oropharyngeal airway directly but also affects the retropalatal airway by a palatoglossal coupling action.¹⁹ Sleep lab testing with polysomnography is used to titrate the voltage of HNS to achieve an open airway that resolves apneic events and normalizes airflow, breathing patterns, and oxygen saturation levels.

Approval of HNS for OSA by the US Food and Drug Administration was based on findings in the Stimulation Therapy for Apnea Reduction (STAR) trial,¹⁷ a prospective trial of 126 patients at 22 centers in the United States and Europe with the primary outcomes of AHI and oxygen desaturation index. Secondary outcomes included quality of life as measured by the Functional Outcomes of Sleep Questionnaire and Epworth Sleepiness Scale (ESS). Patient demographics included mean age 54.5, 83% men, mean BMI of 28 kg/m², and mean baseline AHI of 34 (ie, severe OSA).

Data at 5 years for 97 of the 126 patients on HNS in the STAR trial is available.²⁰ The AHI was reduced an average of 70% to levels in the mild OSA range.^20,21 Overall, 85% of the patients had improved quality-of-life measures after HNS implantation, with increased Functional Outcomes of Sleep Questionnaire scores and ESS scores in the normal range over time. Consistent HNS therapy demonstrated sustained benefits at 5 years. The AHI improved by 50% or to less than 20 in 75% of patients, with 44% having resolved OSA and 78% improved to mild OSA (AHI < 15). Device-related adverse events occurred in 6% (9 of 126) of patients requiring replacement or repositioning of the stimulator or leads.²⁰

Moderate to severe snoring was prevalent at baseline in the STAR trial, but over the course of 5 years, 85% of bed partners of patients on HNS reported no or soft snoring.^17,21 Nightly use averaged 80% over 60 months based on patient reporting, with 87% reporting use at least 5 nights per week at 36 weeks.²⁰

In terms of predictors of response to HNS therapy, the oxygen desaturation index is the only characteristic that reached a level of statistical significance; patients with higher levels of oxygen desaturation tended to improve and tolerate therapy better long-term.²⁰ A randomized controlled trial of withdrawal of HNS therapy demonstrated increased AHI and oxygen desaturation index when therapy was withdrawn, followed by improvement when therapy resumed.²²

A clinical trial of 20 patients implanted with HNS after its approval in 2014 reported that the mean AHI decreased from 33 before implant to 5.1 after implant.²³ The ESS also improved from 10.3 before implant to 6 after implant. Mean adherence to device use was 7 (± 2) hours per night. The average stimulation amplitude was 1.89 (± 0.5) volts after the titration sleep study was completed. Similar reductions in AHI were reported by Huntley et al²⁴ for patients receiving HNS implant at 2 academic centers, with no differences between the 2 cohorts in postoperative AHI.

Adverse events

The adverse events reported with HNS are related to the implant procedure or the device.²¹ Procedure-related adverse events are incision discomfort, temporary tongue weakness, headache, and mild infection of incisions. The most common device-related adverse event is discomfort from the electrical stimulation. Tongue abrasion can also occur if the tongue protrudes and rubs against a sharp tooth. Dry mouth is also commonly reported.

HNS compared with UPPP

Outcomes in patients with moderate to severe OSA matched for BMI, demographics, and preoperative AHI were evaluated comparing patients undergoing HNS (n = 20) with patients receiving UPPP (n = 20).²⁵ The AHI decreased 29% postoperatively in patients with UPPP compared with 88% in patients with HNS, 65% of which had normalization of their AHI. Surgical success was achieved in 40% of patients in the UPPP group compared with 100% in the HNS group. Greater improvement in daytime sleepiness was noted in patients in the HNS group compared with the UPPP group.

OAT devices help protrude the mandible forward and stabilize it to maintain a more patent airway during sleep. Oral appliances can be custom-made or prefabricated. Oral appliances can be titratable or nontitratable: titration provides a mechanism to adjust mandibular protrusion analogous to PAP titration, whereas the absence of titration holds the mandible in a single position. The most effective oral appliances are custom-made and titratable.

Types of OAT devices

Custom oral appliances. Custom oral appliances are fabricated using digital or physical impressions of the patient’s oral structures. Custom oral appliances are made of biocompatible materials and engage both the maxillary and mandibular arches.

Custom oral appliances are made by a qualified dentist who takes maxillary and mandibular impressions with a bite registration using the George Gauge with 40% to 50% of maximum protrusion. The appliance is fabricated in a laboratory and then fitted to the patient, who is instructed to titrate the device 0.5 mm to 1 mm per week and follow-up with the dentist at 2-week intervals. Once the patient has titrated the device to the point of comfort or improved sleep quality or snoring, polysomnography should be done with the device in place and titrated to improve the AHI as much as possible. Follow-up is recommended at 6 months and annually thereafter.

Prefabricated oral appliances. Prefabricated oral appliances are of the boil-and-bite type, only partially modified to the patient’s oral structures.

Tongue-retaining devices. Another type of oral appliance is a tongue-retaining device, which is designed to hold the tongue forward and can be custom-made or prefabricated.

Patient considerations for OAT

Practice recommendations

• Prescribed OAT should be done by a qualified dentist, and a custom, titratable appliance is preferred
• OAT is preferred over no therapy for adults with OSA who are intolerant to PAP or prefer alternative therapies
• A qualified dentist should provide oversight for dental-related side effects or occlusal changes
• Follow-up sleep testing should be conducted to confirm efficacy or titrate treatment
• Periodic office visits with the sleep physician and qualified dentist are recommended.²⁶

The quality of evidence for these recommendations is low, with the exception of use of OAT rather than no therapy, which is considered of moderate quality.

Effects of OAT

Anatomic and physiologic effects. With OAT in place in the mouth, the airway caliber in the lateral dimension are increased, and the airway size at the retropalatal level is increased.^27–30 With respect to the tongue, increased genioglossus muscle activity has been reported with OAT.

Side effects. Side effects of OAT include excess salivation, dry mouth, tooth tenderness, soft-tissue changes, jaw discomfort, tooth movement, and occlusal changes such as difficulty chewing in the morning. Feelings of suffocation, vivid dreams, and anxiety have also been reported with OAT.^31–33

Efficacy and outcomes

Review of the data on the efficacy of OAT did not illuminate factors that predict treatment success.²⁶ Data indicate that in patients with mild OSA using OAT or PAP therapy, there was no significant difference in the percentage achieving their target AHI; however, patients with moderate to severe OSA had a statistically significant greater odds of achieving their target AHI using PAP therapy compared with OAT. Therefore, OAT should be reserved for patients with severe OSA who cannot use or are intolerant to PAP.

Moderate-grade quality of evidence was reviewed for the established OAT practice recommendations for OSA outcomes before and after use of custom, titratable OAT devices.²⁶ Use of a custom OAT device reduced the mean AHI, increased mean oxygen saturation, decreased the mean oxygen desaturation, decreased the arousal index, decreased the ESS, and increased quality of life compared with values prior to use of OAT.

With respect to adherence and discontinuation, patients using OAT had higher mean adherence and lower discontinuation because of side effects compared with patients using continuous PAP.²⁶

Nasal EPAP is a new treatment for OSA that consists of a mechanical valve worn in each naris at night. The valves have a low inspiratory resistance and a high expiratory resistance thus increased pressure occurs at exhalation.

Pressure at exhalation may counter the airway collapse in OSA. With the mouth closed and use of the nasal valves, the positive pressure during the normal respiratory cycle is utilized to maintain an open airway.³⁴ At the onset and throughout inspiration, the activity of the airway dilator muscles increases. At maximum expiration, right before the end of the expiratory pause, the dilator muscle stops abruptly and the airway is of its smallest caliber. The presence of the nasal valve at this point is thought to act as a pneumatic splint to the airway, and the nasal EPAP helps keep the airway patent during the next inspiratory phase.

Nasal EPAP valves are available in a 30-day starter kit. Intended for single-night use, the kit includes valves of increasing levels of expiration resistance: low (nights 1 and 2), medium (nights 3 and 4), and normal (nights 5–30).

Outcomes of nasal EPAP therapy

A multicenter 30-day in-home trial evaluated efficacy and compliance of nasal EPAP therapy.³⁵ The AHI was reduced by 50% or more in 14 of 34 (41%) patients using nasal EPAP compared with the control group at the 30-day follow-up. The patient-reported compliance with nasal EPAP was 94%. Patients in this study had mild to moderate OSA and did not have obesity or other comorbidities such as pulmonary hypertension or cardiovascular disease.

A randomized controlled trial compared nasal EPAP with a sham device in patients with newly diagnosed or untreated OSA (N = 250) for 3 months.³⁶ A median reduction of 52% in the AHI was noted in the intention-to-treat group (N = 229) during rapid eye movement (REM) and non-REM sleep, though it was statistically significant only during REM sleep and supine sleep. At 3 months, improved OSA was maintained in 42% of the patients using nasal EPAP compared with 10% of patients using a sham device. Improvements in daytime sleepiness and adherence with 88% using EPAP the entire night were also noted.

In a 12-month study of nasal EPAP, 67% of patients (34 of 51) used nasal EPAP for the full trial duration.³⁷ Of patients using nasal EPAP for 12 months, the median AHI was reduced by 71%, the ESS improved, and adherence to full-night use was 89%.

Patient considerations for nasal EPAP

In clinical practice, nasal EPAP therapy requires nasal patency and use of a chin strap in patients with mouth leakage. Nasal EPAP may be recommended for patients who travel frequently and can go without continuous PAP or bilevel PAP for short periods of time, and for patients who do not have significant medical comorbidities.

Side effects and limitations of nasal EPAP

Reported side effects of nasal EPAP include difficulty with exhalation, nasal discomfort, dry mouth, and headache. Nasal EPAP therapy is of limited use in patients with severe OSA and severe oxygen desaturation. The efficacy of nasal EPAP beyond 12 months is unknown. Use of nasal EPAP in patients with prior upper-airway surgery and in combination with other therapies is yet to be evaluated.

The most widely used treatment for patients with obstructive sleep apnea (OSA) is positive airway pressure (PAP) therapy. Improved quality of life and cardiovascular outcomes for patients with OSA using PAP have been demonstrated. However, for some patients with OSA, PAP therapy is difficult to use or tolerate. Fortunately, there are other available treatment interventions for patients with OSA such as lifestyle interventions, surgical interventions, hypoglossal nerve stimulation (HNS), oral appliance therapy (OAT), and expiratory PAP (EPAP) devices. These alternative treatments can also improve symptoms of OSA though data regarding cardiovascular outcomes are lacking.

LIFESTYLE INTERVENTIONS

Weight loss

Because a higher body mass index (BMI) increases the risk for OSA, weight loss should be recommended for patients with OSA who are overweight. Much of the research evaluating the effect of weight loss on OSA has methodologic limitations such as lack of randomization or controls, potential confounding variables, and limited follow-up. A randomized controlled trial of 72 overweight patients with mild OSA (apnea–hypopnea index [AHI] of 5 to 15) compared a group assigned to a very low calorie diet and lifestyle counseling with a control group.¹ At 1 year, weight loss of 15 kg or more resulted in a statistically significant reduction in their AHI to normal, resolving their OSA. A 15 kg weight loss in this study was associated with an overall reduction in the AHI of at least 2 units.

Exercise

Exercise is also recommended for patients with OSA, and it can lessen the severity of symptoms even without weight loss. A meta-analysis of 5 randomized trials of 129 patients reported a reduction in the AHI of as much as 6 events per hour in individuals assigned to a strict exercise regimen.² The reduction in the AHI occurred despite a slight reduction in BMI (1.37 kg/m²).

Sleep position

For some patients, sleeping in the supine position may worsen their OSA, in which case avoiding the supine sleep position is recommended. A sleep study such as polysomnography should be performed to confirm the resolution of OSA in the nonsupine position.³ Products such as pillows or vibratory feedback devices can help the patient avoid sleeping on the back. The ability to monitor patient adherence to sleep position therapy alone is very limited.

Alcohol avoidance

Alcohol consumption depresses the central nervous system, promotes waking, and increases daytime sleepiness, thus exacerbating OSA. Patients with untreated OSA should avoid alcohol because it worsens the duration and frequency of obstructive respiratory events during sleep, and it can worsen the degree of oxygen desaturation that occurs during abnormal respiratory events.⁴

Concomitant medications

A review of medications in patients with OSA is warranted. Use of benzodiazepines, benzodiazepine-receptor agonists, barbiturates, and opiates in patients with OSA should be avoided especially if OSA is untreated. If these medications are necessary, careful monitoring is recommended. Medications that can cause weight gain such as some antidepressants should also be avoided.

SURGICAL INTERVENTIONS

Surgical interventions for OSA target the location of the obstruction in the upper airway. The upper airway consists of 3 regions: the palate, oropharynx, and larynx.⁵ More than 30 surgical soft-tissue and skeletal interventions for OSA are reported in the literature.⁶

Evaluating the outcomes of various surgical interventions for OSA is hindered by differences in the definition of surgical success or cure. As such, surgical interventions for OSA remain controversial. The practice parameters from 2010 reviewed surgical modifications of the upper airway for adults with OSA.^7,8 Success is defined as a greater than 50% reduction in the AHI to fewer than 20 events per hour, whereas surgical cure is defined as a reduction in the AHI to fewer than 5 events per hour.⁷

Uvulopalatopharyngoplasty

Uvulopalatopharyngoplasty (UPPP) is a surgical procedure that remodels the throat via removal of the tonsils and the posterior surface of the soft palate and uvula and closure of the tonsillar pillars, and thus addresses retropalatal collapse. UPPP rarely achieves a surgical cure (ie, AHI < 5) and has been shown to have a 33% reduction in the AHI, with a postoperative average AHI remaining elevated at 29.⁸ (ie, moderate to severe OSA).8 In general, 50% of patients have a 50% reduction in AHI.⁹ The 4-year responder rate for UPPP is 44% to 50%.¹⁰ Factors limiting the long-term success of this procedure include weight gain, assessment of surgical candidates,¹¹ and decreased adherence to PAP therapy after the procedure.

The use of UPPP in combination with other surgical procedures has also been evaluated.⁸ The AHI in patients with OSA improved postoperatively when UPPP was done simultaneously or in a multiphase approach with radiofrequency ablation, midline glossectomy, tongue advancement, hyoid suspension, or maxillomandibular advancement, though greater improvement was noted with the multiphase approach.

Maxillomandibular advancement

Maxillomandibular advancement is a surgical procedure that moves the maxilla and mandible forward and expands the facial skeletal framework via LeFort I maxillary and sagittal split mandibular osteotomies. Maxillomandibular advancement achieves enlargement of the nasopharyngeal, retropalatal, and hypopharyngeal airway. This increases tension on the pharyngeal soft tissue, which enlarges the medial-lateral and anteroposterior dimensions of the upper airway.¹⁴

A meta-analysis of 45 studies evaluated the change in the AHI after maxillomandibular advancement in 518 patients.¹⁵ Secondary outcomes were surgical success (> 50% reduction in AHI to < 20 events per hour) and surgical cure (AHI < 5). Patients with a higher preoperative AHI achieved the greatest magnitude reduction in AHI but were less likely to achieve surgical success or cure. Patients with a lower preoperative AHI had a greater likelihood of surgical success and cure.

Bariatric surgery

Bariatric surgery is increasingly used for treatment of OSA in individuals with morbid obesity. A systematic review of bariatric surgery including the roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and biliopancreatic diversion evaluated 69 studies with 13,900 patients with OSA.¹⁶ OSA was found to be improved or eliminated in 75% of patients for all bariatric surgery procedures.

Used with permission from Inspire Medical Systems, Inc.

Indications and contraindications

The indications and contraindications for HNS are shown in Table 2.

Efficacy and outcomes

Stimulation of the hypoglossal nerve results in a multilevel mechanism of action: activation and protrusion of the tongue opens the oropharyngeal airway directly but also affects the retropalatal airway by a palatoglossal coupling action.¹⁹ Sleep lab testing with polysomnography is used to titrate the voltage of HNS to achieve an open airway that resolves apneic events and normalizes airflow, breathing patterns, and oxygen saturation levels.

Approval of HNS for OSA by the US Food and Drug Administration was based on findings in the Stimulation Therapy for Apnea Reduction (STAR) trial,¹⁷ a prospective trial of 126 patients at 22 centers in the United States and Europe with the primary outcomes of AHI and oxygen desaturation index. Secondary outcomes included quality of life as measured by the Functional Outcomes of Sleep Questionnaire and Epworth Sleepiness Scale (ESS). Patient demographics included mean age 54.5, 83% men, mean BMI of 28 kg/m², and mean baseline AHI of 34 (ie, severe OSA).

Data at 5 years for 97 of the 126 patients on HNS in the STAR trial is available.²⁰ The AHI was reduced an average of 70% to levels in the mild OSA range.^20,21 Overall, 85% of the patients had improved quality-of-life measures after HNS implantation, with increased Functional Outcomes of Sleep Questionnaire scores and ESS scores in the normal range over time. Consistent HNS therapy demonstrated sustained benefits at 5 years. The AHI improved by 50% or to less than 20 in 75% of patients, with 44% having resolved OSA and 78% improved to mild OSA (AHI < 15). Device-related adverse events occurred in 6% (9 of 126) of patients requiring replacement or repositioning of the stimulator or leads.²⁰

Moderate to severe snoring was prevalent at baseline in the STAR trial, but over the course of 5 years, 85% of bed partners of patients on HNS reported no or soft snoring.^17,21 Nightly use averaged 80% over 60 months based on patient reporting, with 87% reporting use at least 5 nights per week at 36 weeks.²⁰

In terms of predictors of response to HNS therapy, the oxygen desaturation index is the only characteristic that reached a level of statistical significance; patients with higher levels of oxygen desaturation tended to improve and tolerate therapy better long-term.²⁰ A randomized controlled trial of withdrawal of HNS therapy demonstrated increased AHI and oxygen desaturation index when therapy was withdrawn, followed by improvement when therapy resumed.²²

A clinical trial of 20 patients implanted with HNS after its approval in 2014 reported that the mean AHI decreased from 33 before implant to 5.1 after implant.²³ The ESS also improved from 10.3 before implant to 6 after implant. Mean adherence to device use was 7 (± 2) hours per night. The average stimulation amplitude was 1.89 (± 0.5) volts after the titration sleep study was completed. Similar reductions in AHI were reported by Huntley et al²⁴ for patients receiving HNS implant at 2 academic centers, with no differences between the 2 cohorts in postoperative AHI.

Adverse events

The adverse events reported with HNS are related to the implant procedure or the device.²¹ Procedure-related adverse events are incision discomfort, temporary tongue weakness, headache, and mild infection of incisions. The most common device-related adverse event is discomfort from the electrical stimulation. Tongue abrasion can also occur if the tongue protrudes and rubs against a sharp tooth. Dry mouth is also commonly reported.

HNS compared with UPPP

Outcomes in patients with moderate to severe OSA matched for BMI, demographics, and preoperative AHI were evaluated comparing patients undergoing HNS (n = 20) with patients receiving UPPP (n = 20).²⁵ The AHI decreased 29% postoperatively in patients with UPPP compared with 88% in patients with HNS, 65% of which had normalization of their AHI. Surgical success was achieved in 40% of patients in the UPPP group compared with 100% in the HNS group. Greater improvement in daytime sleepiness was noted in patients in the HNS group compared with the UPPP group.

OAT devices help protrude the mandible forward and stabilize it to maintain a more patent airway during sleep. Oral appliances can be custom-made or prefabricated. Oral appliances can be titratable or nontitratable: titration provides a mechanism to adjust mandibular protrusion analogous to PAP titration, whereas the absence of titration holds the mandible in a single position. The most effective oral appliances are custom-made and titratable.

Types of OAT devices

Custom oral appliances. Custom oral appliances are fabricated using digital or physical impressions of the patient’s oral structures. Custom oral appliances are made of biocompatible materials and engage both the maxillary and mandibular arches.

Custom oral appliances are made by a qualified dentist who takes maxillary and mandibular impressions with a bite registration using the George Gauge with 40% to 50% of maximum protrusion. The appliance is fabricated in a laboratory and then fitted to the patient, who is instructed to titrate the device 0.5 mm to 1 mm per week and follow-up with the dentist at 2-week intervals. Once the patient has titrated the device to the point of comfort or improved sleep quality or snoring, polysomnography should be done with the device in place and titrated to improve the AHI as much as possible. Follow-up is recommended at 6 months and annually thereafter.

Prefabricated oral appliances. Prefabricated oral appliances are of the boil-and-bite type, only partially modified to the patient’s oral structures.

Tongue-retaining devices. Another type of oral appliance is a tongue-retaining device, which is designed to hold the tongue forward and can be custom-made or prefabricated.

Patient considerations for OAT

Practice recommendations

• Prescribed OAT should be done by a qualified dentist, and a custom, titratable appliance is preferred
• OAT is preferred over no therapy for adults with OSA who are intolerant to PAP or prefer alternative therapies
• A qualified dentist should provide oversight for dental-related side effects or occlusal changes
• Follow-up sleep testing should be conducted to confirm efficacy or titrate treatment
• Periodic office visits with the sleep physician and qualified dentist are recommended.²⁶

The quality of evidence for these recommendations is low, with the exception of use of OAT rather than no therapy, which is considered of moderate quality.

Effects of OAT

Anatomic and physiologic effects. With OAT in place in the mouth, the airway caliber in the lateral dimension are increased, and the airway size at the retropalatal level is increased.^27–30 With respect to the tongue, increased genioglossus muscle activity has been reported with OAT.

Side effects. Side effects of OAT include excess salivation, dry mouth, tooth tenderness, soft-tissue changes, jaw discomfort, tooth movement, and occlusal changes such as difficulty chewing in the morning. Feelings of suffocation, vivid dreams, and anxiety have also been reported with OAT.^31–33

Efficacy and outcomes

Review of the data on the efficacy of OAT did not illuminate factors that predict treatment success.²⁶ Data indicate that in patients with mild OSA using OAT or PAP therapy, there was no significant difference in the percentage achieving their target AHI; however, patients with moderate to severe OSA had a statistically significant greater odds of achieving their target AHI using PAP therapy compared with OAT. Therefore, OAT should be reserved for patients with severe OSA who cannot use or are intolerant to PAP.

Moderate-grade quality of evidence was reviewed for the established OAT practice recommendations for OSA outcomes before and after use of custom, titratable OAT devices.²⁶ Use of a custom OAT device reduced the mean AHI, increased mean oxygen saturation, decreased the mean oxygen desaturation, decreased the arousal index, decreased the ESS, and increased quality of life compared with values prior to use of OAT.

With respect to adherence and discontinuation, patients using OAT had higher mean adherence and lower discontinuation because of side effects compared with patients using continuous PAP.²⁶

Nasal EPAP is a new treatment for OSA that consists of a mechanical valve worn in each naris at night. The valves have a low inspiratory resistance and a high expiratory resistance thus increased pressure occurs at exhalation.

Pressure at exhalation may counter the airway collapse in OSA. With the mouth closed and use of the nasal valves, the positive pressure during the normal respiratory cycle is utilized to maintain an open airway.³⁴ At the onset and throughout inspiration, the activity of the airway dilator muscles increases. At maximum expiration, right before the end of the expiratory pause, the dilator muscle stops abruptly and the airway is of its smallest caliber. The presence of the nasal valve at this point is thought to act as a pneumatic splint to the airway, and the nasal EPAP helps keep the airway patent during the next inspiratory phase.

Nasal EPAP valves are available in a 30-day starter kit. Intended for single-night use, the kit includes valves of increasing levels of expiration resistance: low (nights 1 and 2), medium (nights 3 and 4), and normal (nights 5–30).

Outcomes of nasal EPAP therapy

A multicenter 30-day in-home trial evaluated efficacy and compliance of nasal EPAP therapy.³⁵ The AHI was reduced by 50% or more in 14 of 34 (41%) patients using nasal EPAP compared with the control group at the 30-day follow-up. The patient-reported compliance with nasal EPAP was 94%. Patients in this study had mild to moderate OSA and did not have obesity or other comorbidities such as pulmonary hypertension or cardiovascular disease.

A randomized controlled trial compared nasal EPAP with a sham device in patients with newly diagnosed or untreated OSA (N = 250) for 3 months.³⁶ A median reduction of 52% in the AHI was noted in the intention-to-treat group (N = 229) during rapid eye movement (REM) and non-REM sleep, though it was statistically significant only during REM sleep and supine sleep. At 3 months, improved OSA was maintained in 42% of the patients using nasal EPAP compared with 10% of patients using a sham device. Improvements in daytime sleepiness and adherence with 88% using EPAP the entire night were also noted.

In a 12-month study of nasal EPAP, 67% of patients (34 of 51) used nasal EPAP for the full trial duration.³⁷ Of patients using nasal EPAP for 12 months, the median AHI was reduced by 71%, the ESS improved, and adherence to full-night use was 89%.

Patient considerations for nasal EPAP

In clinical practice, nasal EPAP therapy requires nasal patency and use of a chin strap in patients with mouth leakage. Nasal EPAP may be recommended for patients who travel frequently and can go without continuous PAP or bilevel PAP for short periods of time, and for patients who do not have significant medical comorbidities.

Side effects and limitations of nasal EPAP

Reported side effects of nasal EPAP include difficulty with exhalation, nasal discomfort, dry mouth, and headache. Nasal EPAP therapy is of limited use in patients with severe OSA and severe oxygen desaturation. The efficacy of nasal EPAP beyond 12 months is unknown. Use of nasal EPAP in patients with prior upper-airway surgery and in combination with other therapies is yet to be evaluated.

Supplement Editor:
Nancy Foldvary-Schaefer

Contents

Introduction—Obstructive sleep apnea: A wake-up call for better outcomes
Nancy Foldvary-Schaefer

Obstructive sleep apnea basics
Jessica Vensel Rundo

Sleep apnea and the heart
Reena Mehra

Beyond heart health: Consequences of obstructive sleep apnea
Harneet K. Walia

Positive airway pressure: Making an impact on sleep apnea
Colleen G. Lance

Alternative interventions for obstructive sleep apnea
Tina Waters

Click for related Cleveland Clinic CME activities.

Supplement Editor:
Nancy Foldvary-Schaefer

Contents

Introduction—Obstructive sleep apnea: A wake-up call for better outcomes
Nancy Foldvary-Schaefer

Obstructive sleep apnea basics
Jessica Vensel Rundo

Sleep apnea and the heart
Reena Mehra

Beyond heart health: Consequences of obstructive sleep apnea
Harneet K. Walia

Positive airway pressure: Making an impact on sleep apnea
Colleen G. Lance

Alternative interventions for obstructive sleep apnea
Tina Waters

Click for related Cleveland Clinic CME activities.

Supplement Editor:
Nancy Foldvary-Schaefer

Contents

Introduction—Obstructive sleep apnea: A wake-up call for better outcomes
Nancy Foldvary-Schaefer

Obstructive sleep apnea basics
Jessica Vensel Rundo

Sleep apnea and the heart
Reena Mehra

Beyond heart health: Consequences of obstructive sleep apnea
Harneet K. Walia

Positive airway pressure: Making an impact on sleep apnea
Colleen G. Lance

Alternative interventions for obstructive sleep apnea
Tina Waters

Click for related Cleveland Clinic CME activities.

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

Insomnia, sleep-related disordered breathing, and nightmares were associated with suicide attempts in a large case-control matched study of patients in the Veterans Health Administration database.

However, treatment for sleep disorders was correlated to a reduced risk for suicide attempts.

Todd M. Bishop, PhD, of the Center of Excellence for Suicide Prevention, Canandaigua (N.Y.) VA Medical Center, and the department of psychiatry, University of Rochester (N.Y.) Medical Center, and his colleagues wrote that suicide is the 10th most frequent cause of death in the United States, and “nowhere is the suicide rate more alarming than among military veterans, who after adjusting for age and gender, have an approximately 1.5 times greater risk for suicide as compared to the civilian population.”

Previous research has explored the link between sleep disturbances and suicide attempts. But less has been done to look at specific sleep problems, and little research has examined the role of sleep medicine interventions and suicide attempt risk.

The investigators conducted a study to establish the association between suicide attempts and specific sleep disorders, and to examine the correlation between sleep medicine treatment and suicide attempts. Their sample consisted of 60,102 veterans who had received care within the VHA between Oct. 1, 2012, and Sept. 20, 2014. Half of the sample had a documented suicide attempt in the medical record (n = 30,051) and half did not (n = 30,051). The overall sample was predominately male (87.1%) with a mean age of 48.6 years. More than half the sample identified as white (67.4%).

Suicide attempts, sleep disturbance, and medical and mental health comorbidities were identified via ICD codes and prescription records. The predominant sleep disorders studied were insomnia, sleep-related breathing disorder (SRBD), and nightmares. The first suicide attempt in the study period was determined to be the index date for the case-control matching.

Overall, sleep disturbances were much more prevalent among cases than controls (insomnia, 46.2% vs. 12.6%), sleep-related breathing disorder (8.6% vs. 4.8%), and nightmares (7.1% vs. 1.6%). A logistic regression analysis was undertaken to examine the relationship between specific sleep disorders and suicide attempts. Insomnia, nightmares, and SRBD were each associated with increased odds of a suicide attempt with the following odds ratios: insomnia (odds ratio, 5.62; 95% confidence interval, 5.39-5.86), nightmares (OR, 2.49; 95% CI, 2.23-2.77), and sleep-related breathing disorder (OR, 1.37; 95% CI, 1.27-1.48).

A second model included known drivers of suicide attempts (PTSD, depression, anxiety disorders, schizophrenia, bipolar disorder, substance use disorder, medical comorbidity, and obesity). But after controlling for these factors, neither nightmares (OR, 0.96; 95% CI, 0.85-1.09) nor sleep-related breathing disorders (OR, 0.87, 95% CI, 0.79-0.94) remained positively associated with suicide attempt, but the association of insomnia with suicide attempt was maintained (OR, 1.51; 95% CI, 1.43-1.59).

The question of the impact of sleep medicine interventions on suicide attempts was studied with a third regression model adding the number of sleep medicine clinic visits in the 180 days prior to the suicide attempt index date as an independent variable. The variables in this model were limited to insomnia, SRBD, and nightmares. The investigators found that “for each sleep medicine clinic visit within the 6 months prior to index date the likelihood of suicide attempt is 11% less (OR, 0.89; 95% CI, 0.82-0.97).”

The limitations of the study include the lack of information on sleep treatment modalities or medications provided during the clinic visits, and the overlapping of sleep disturbance with other mental health conditions, such as alcohol dependence and PTSD. In addition, “some insomnia medications are labeled for risk of suicidal ideation and behavior, so there is some chance that the medications rather than insomnia itself were associated with the increased suicidal behavior,” the investigators wrote.

In addition to an analysis of specific types of sleep disorders associated with suicide attempts, the study showed that treatment of sleep disorders may have an important role in suicide prevention. The investigators concluded: “Identifying populations at risk for suicide prior to a first attempt is an important, but difficult task of suicide prevention. Prevention efforts can be aimed at modifiable risk factors that arise early on a patient’s trajectory toward a suicide attempt.”

The study was supported by the VISN 2 Center of Excellence for Suicide Prevention, Canandaigua VAMC. The authors had no disclosures.

[email protected]

SOURCE: Bishop TM et al. Sleep Med. 2019 Jul 25. doi: 10.1016/j.sleep.2019.07.016.

Insomnia, sleep-related disordered breathing, and nightmares were associated with suicide attempts in a large case-control matched study of patients in the Veterans Health Administration database.

However, treatment for sleep disorders was correlated to a reduced risk for suicide attempts.

Todd M. Bishop, PhD, of the Center of Excellence for Suicide Prevention, Canandaigua (N.Y.) VA Medical Center, and the department of psychiatry, University of Rochester (N.Y.) Medical Center, and his colleagues wrote that suicide is the 10th most frequent cause of death in the United States, and “nowhere is the suicide rate more alarming than among military veterans, who after adjusting for age and gender, have an approximately 1.5 times greater risk for suicide as compared to the civilian population.”

Previous research has explored the link between sleep disturbances and suicide attempts. But less has been done to look at specific sleep problems, and little research has examined the role of sleep medicine interventions and suicide attempt risk.

The investigators conducted a study to establish the association between suicide attempts and specific sleep disorders, and to examine the correlation between sleep medicine treatment and suicide attempts. Their sample consisted of 60,102 veterans who had received care within the VHA between Oct. 1, 2012, and Sept. 20, 2014. Half of the sample had a documented suicide attempt in the medical record (n = 30,051) and half did not (n = 30,051). The overall sample was predominately male (87.1%) with a mean age of 48.6 years. More than half the sample identified as white (67.4%).

Suicide attempts, sleep disturbance, and medical and mental health comorbidities were identified via ICD codes and prescription records. The predominant sleep disorders studied were insomnia, sleep-related breathing disorder (SRBD), and nightmares. The first suicide attempt in the study period was determined to be the index date for the case-control matching.

Overall, sleep disturbances were much more prevalent among cases than controls (insomnia, 46.2% vs. 12.6%), sleep-related breathing disorder (8.6% vs. 4.8%), and nightmares (7.1% vs. 1.6%). A logistic regression analysis was undertaken to examine the relationship between specific sleep disorders and suicide attempts. Insomnia, nightmares, and SRBD were each associated with increased odds of a suicide attempt with the following odds ratios: insomnia (odds ratio, 5.62; 95% confidence interval, 5.39-5.86), nightmares (OR, 2.49; 95% CI, 2.23-2.77), and sleep-related breathing disorder (OR, 1.37; 95% CI, 1.27-1.48).

A second model included known drivers of suicide attempts (PTSD, depression, anxiety disorders, schizophrenia, bipolar disorder, substance use disorder, medical comorbidity, and obesity). But after controlling for these factors, neither nightmares (OR, 0.96; 95% CI, 0.85-1.09) nor sleep-related breathing disorders (OR, 0.87, 95% CI, 0.79-0.94) remained positively associated with suicide attempt, but the association of insomnia with suicide attempt was maintained (OR, 1.51; 95% CI, 1.43-1.59).

The question of the impact of sleep medicine interventions on suicide attempts was studied with a third regression model adding the number of sleep medicine clinic visits in the 180 days prior to the suicide attempt index date as an independent variable. The variables in this model were limited to insomnia, SRBD, and nightmares. The investigators found that “for each sleep medicine clinic visit within the 6 months prior to index date the likelihood of suicide attempt is 11% less (OR, 0.89; 95% CI, 0.82-0.97).”

The limitations of the study include the lack of information on sleep treatment modalities or medications provided during the clinic visits, and the overlapping of sleep disturbance with other mental health conditions, such as alcohol dependence and PTSD. In addition, “some insomnia medications are labeled for risk of suicidal ideation and behavior, so there is some chance that the medications rather than insomnia itself were associated with the increased suicidal behavior,” the investigators wrote.

In addition to an analysis of specific types of sleep disorders associated with suicide attempts, the study showed that treatment of sleep disorders may have an important role in suicide prevention. The investigators concluded: “Identifying populations at risk for suicide prior to a first attempt is an important, but difficult task of suicide prevention. Prevention efforts can be aimed at modifiable risk factors that arise early on a patient’s trajectory toward a suicide attempt.”

The study was supported by the VISN 2 Center of Excellence for Suicide Prevention, Canandaigua VAMC. The authors had no disclosures.

[email protected]

SOURCE: Bishop TM et al. Sleep Med. 2019 Jul 25. doi: 10.1016/j.sleep.2019.07.016.

Insomnia, sleep-related disordered breathing, and nightmares were associated with suicide attempts in a large case-control matched study of patients in the Veterans Health Administration database.

However, treatment for sleep disorders was correlated to a reduced risk for suicide attempts.

Todd M. Bishop, PhD, of the Center of Excellence for Suicide Prevention, Canandaigua (N.Y.) VA Medical Center, and the department of psychiatry, University of Rochester (N.Y.) Medical Center, and his colleagues wrote that suicide is the 10th most frequent cause of death in the United States, and “nowhere is the suicide rate more alarming than among military veterans, who after adjusting for age and gender, have an approximately 1.5 times greater risk for suicide as compared to the civilian population.”

Previous research has explored the link between sleep disturbances and suicide attempts. But less has been done to look at specific sleep problems, and little research has examined the role of sleep medicine interventions and suicide attempt risk.

The investigators conducted a study to establish the association between suicide attempts and specific sleep disorders, and to examine the correlation between sleep medicine treatment and suicide attempts. Their sample consisted of 60,102 veterans who had received care within the VHA between Oct. 1, 2012, and Sept. 20, 2014. Half of the sample had a documented suicide attempt in the medical record (n = 30,051) and half did not (n = 30,051). The overall sample was predominately male (87.1%) with a mean age of 48.6 years. More than half the sample identified as white (67.4%).

Suicide attempts, sleep disturbance, and medical and mental health comorbidities were identified via ICD codes and prescription records. The predominant sleep disorders studied were insomnia, sleep-related breathing disorder (SRBD), and nightmares. The first suicide attempt in the study period was determined to be the index date for the case-control matching.

Overall, sleep disturbances were much more prevalent among cases than controls (insomnia, 46.2% vs. 12.6%), sleep-related breathing disorder (8.6% vs. 4.8%), and nightmares (7.1% vs. 1.6%). A logistic regression analysis was undertaken to examine the relationship between specific sleep disorders and suicide attempts. Insomnia, nightmares, and SRBD were each associated with increased odds of a suicide attempt with the following odds ratios: insomnia (odds ratio, 5.62; 95% confidence interval, 5.39-5.86), nightmares (OR, 2.49; 95% CI, 2.23-2.77), and sleep-related breathing disorder (OR, 1.37; 95% CI, 1.27-1.48).

A second model included known drivers of suicide attempts (PTSD, depression, anxiety disorders, schizophrenia, bipolar disorder, substance use disorder, medical comorbidity, and obesity). But after controlling for these factors, neither nightmares (OR, 0.96; 95% CI, 0.85-1.09) nor sleep-related breathing disorders (OR, 0.87, 95% CI, 0.79-0.94) remained positively associated with suicide attempt, but the association of insomnia with suicide attempt was maintained (OR, 1.51; 95% CI, 1.43-1.59).

The question of the impact of sleep medicine interventions on suicide attempts was studied with a third regression model adding the number of sleep medicine clinic visits in the 180 days prior to the suicide attempt index date as an independent variable. The variables in this model were limited to insomnia, SRBD, and nightmares. The investigators found that “for each sleep medicine clinic visit within the 6 months prior to index date the likelihood of suicide attempt is 11% less (OR, 0.89; 95% CI, 0.82-0.97).”

The limitations of the study include the lack of information on sleep treatment modalities or medications provided during the clinic visits, and the overlapping of sleep disturbance with other mental health conditions, such as alcohol dependence and PTSD. In addition, “some insomnia medications are labeled for risk of suicidal ideation and behavior, so there is some chance that the medications rather than insomnia itself were associated with the increased suicidal behavior,” the investigators wrote.

In addition to an analysis of specific types of sleep disorders associated with suicide attempts, the study showed that treatment of sleep disorders may have an important role in suicide prevention. The investigators concluded: “Identifying populations at risk for suicide prior to a first attempt is an important, but difficult task of suicide prevention. Prevention efforts can be aimed at modifiable risk factors that arise early on a patient’s trajectory toward a suicide attempt.”

The study was supported by the VISN 2 Center of Excellence for Suicide Prevention, Canandaigua VAMC. The authors had no disclosures.

[email protected]

SOURCE: Bishop TM et al. Sleep Med. 2019 Jul 25. doi: 10.1016/j.sleep.2019.07.016.

LOS ANGELES – While a large number of older adults take prescription and nonprescription medications to help them sleep, the effect of these medications on dementia risk is unclear, with most researchers advocating a cautious and conservative approach to prescribing.

Nastasic/iStockphoto.com

Research is increasingly revealing a bidirectional relationship between sleep and dementia. Poor sleep – especially from insomnia, sleep deprivation, or obstructive sleep apnea – is known to increase dementia risk. Dementias, meanwhile, are associated with serious circadian rhythm disturbances, leading to nighttime sleep loss and increasing the likelihood of institutionalization.

At the Alzheimer’s Association International Conference, researchers presented findings assessing the links between sleep medication use and dementia and also what agents or approaches might safely improve sleep in people with sleep disorders who are at risk for dementia or who have been diagnosed with dementia.
 

Sex- and race-based differences in risk

Yue Leng, PhD, of the University of California, San Francisco, reported a link between frequent sleep medication use and later dementia – but only in white adults. Dr. Leng presented findings from the National Institutes of Health–funded Health, Aging, and Body Composition Study, which recruited 3,068 subjects aged 70-79 and followed them for 15 years. At baseline, 2.7% of African Americans and 7.7% of whites in the study reported taking sleep medications “often” or “almost always.”

Dr. Leng and her colleagues found that white subjects who reported taking sleep aids five or more times a month at baseline had a nearly 80% higher risk of developing dementia during the course of the study (hazard ratio, 1.79; 95% confidence interval, 1.21-2.66), compared with people who reported never taking sleep aids or taking them less frequently.

The researchers saw no between-sex differences for this finding, and adjusted for a variety of genetic and lifestyle confounders. Importantly, no significant increase in dementia risk was seen for black subjects, who made up more than one-third of the cohort.

Dr. Leng told the conference that the researchers could not explain why black participants did not see similarly increased dementia risk. Also, she noted, researchers did not have information on the specific sleep medications people used: benzodiazepines, antihistamines, antidepressants, or other types of drugs. Nonetheless, she told the conference, the findings ratified the cautious approach many dementia experts are already stressing.


“Do we really need to prescribe so many sleep meds to older adults who are already at risk for cognitive impairment?” Dr. Leng said, adding: “I am a big advocate of behavioral sleep interventions.” People with clinical sleep problems “should be referred to sleep centers” for a fuller assessment before medication is prescribed, she said.

Findings from another cohort study, meanwhile, suggest that there could be sex-related differences in how sleep aids affect dementia risk. Investigators at Utah State University in Logan used data from some 3,656 older adults in the Cache County Study on Memory and Aging, an NIH-backed cohort study of white adults in Utah without dementia at baseline who were followed for 12 years.

The investigators, led by doctoral student Elizabeth Vernon, found that men reporting use of sleep medication saw more than threefold higher risk of developing Alzheimer’s disease than did men who did not use sleep aids (HR, 3.604; P = .0001).

Women who did not report having sleep disturbance but used sleep-inducing medications were at nearly fourfold greater risk for developing Alzheimer’s disease (HR, 3.916; P = .0001). Women who self-reported sleep disturbances at baseline, meanwhile, saw a reduction in Alzheimer’s risk of about one-third associated with the use of sleep medications.

Ms. Vernon told the conference that, despite the finding of risk reduction for this particular group of women, caution in prescribing sleep aids was warranted.

Common sleep drugs linked to cognitive aging

Chris Fox, MD, a researcher at the University of East Anglia in Norwich, England, and his colleagues demonstrated in 2018 that long-term exposure to anticholinergic drugs, a class that includes some antidepressants and antihistamines used to promote sleep, was associated with a higher risk of dementia, while use of benzodiazepines, a class of sedatives used commonly in older people as sleep aids, was not. (Whether benzodiazepine exposure relates to dementia remains controversial.)

At AAIC 2019, Dr. Fox presented findings from a study of 337 brains in a U.K. brain bank, of which 17% and 21% came from users of benzodiazepines and anticholinergic drugs, whose usage history was well documented. Dr. Fox and his colleagues found that, while neither anticholinergic nor benzodiazepine exposure was associated with brain pathology specific to that seen in Alzheimer’s disease, both classes of drugs were associated with “slight signals in neuronal loss” in one brain region, the nucleus basalis of Meynert. Dr. Fox described the drugs as causing “an increase in cognitive aging” which could bear on Alzheimer’s risk without being directly causative.
 

Newer sleep drugs may help Alzheimer’s patients

Scientists working for drug manufacturers presented findings on agents to counter the circadian rhythm disturbances seen in people with Alzheimer’s disease. Margaret Moline, PhD, of Eisai in Woodcliff Lake, N.J., showed some results from a phase 2, dose-ranging, placebo-controlled study of the experimental agent lemborexant in 62 subjects aged 60-90 with mild to moderate Alzheimer’s disease and sleep disturbances. (Lemborexant, an orexin receptor agonist that acts to regulate wakefulness, is being investigated in a broad range of sleep disorders.) Patients were randomized to one of four doses of lemborexant or placebo and wore a device for sleep monitoring. Nighttime activity indicating arousal was significantly lower for people in two dosage arms, 5 mg and 10 mg, compared with placebo, and treatment groups saw trends toward less sleep fragmentation and higher total sleep time, Dr. Moline told the conference.

Suvorexant (Belsomra), the only orexin receptor antagonist currently licensed as a sleep aid, is also being tested in people with Alzheimer’s disease. At AAIC 2019, Joseph Herring, MD, PhD, of Merck in Kenilworth, N.J., presented results from a placebo-controlled trial of 277 patients with Alzheimer’s disease and insomnia, and reported that treatment with 10 or 20 mg of suvorexant over 4 weeks was associated with about an extra half hour of total nightly sleep, with a 73-minute mean increase from baseline, compared with 45 minutes for patients receiving placebo (95% CI, 11-45; P less than .005).
 

Trazodone linked to slower cognitive decline

An inexpensive antidepressant used in low doses as a sleep aid, including in people with Alzheimer’s disease, was associated with a delay in cognitive decline in older adults, according to results from a retrospective study. Elissaios Karageorgiou, MD, PhD, of the University of California, San Francisco, and the Neurological Institute of Athens presented results derived from two cohorts: patients enrolled at the UCSF Memory and Aging Center and women enrolled in the Study for Osteoporotic Fractures (SOF) in Women. The investigators were able to identify trazodone users in the studies (with two or more contiguous study visits reporting trazodone use) and match them with control patients from the same cohorts who did not use trazodone.

Trazodone was studied because previous research suggests it increases total sleep time in patients with Alzheimer’s disease without affecting next-day cognitive performance.

Trazodone-using patients in the UCSF cohort (n = 25) saw significantly less decline in Mini Mental State Exam (MMSE) scores over 4 years, compared with nonusers (0.27 vs. 0.70 points per year; P = .023), an effect that remained statistically significant even after adjusting for sedative and stimulant use and the expected progression of Alzheimer’s disease pathology. Importantly, the slower decline was seen only among subjects with sleep complaints at baseline and especially those whose sleep improved over time, suggesting that the cognitive benefit was mediated by improved sleep.

In the SOF cohort of 46 trazodone users matched with 148 nonusers, no significant protective or negative effect related to long-term trazodone use was found using the MMSE or the Trails Making Test. In this analysis, however, baseline and longitudinal sleep quality was not captured in the group-matching process, neither was the use of other medications. The patient group was slightly older, and all patients were women.

Dr. Karageorgiou said in an interview that the link between improved sleep, trazodone, and cognition needs to be validated in prospective intervention studies. Trazodone, he said, appears to work best in people with a specific type of insomnia characterized by cortical and behavioral hyperarousal, and its cognitive effect appears limited to people whose sleep improves with treatment. “You’re not going to see long-term cognitive benefits if it’s not improving your sleep,” Dr. Karageorgiou said. “So, whether trazodone improves sleep or not in a patient after a few months can be an early indicator for the clinician to continue using it or suspend it, because it is unlikely to help their cognition otherwise.”

He stressed that physicians need to be broadly focused on improving sleep to help patients with, or at risk for, dementia by consolidating their sleep rhythms.

“Trazodone is not the magic bullet, and I don’t think we will ever have a magic bullet,” Dr. Karageorgiou said. “Because when our brain degenerates, it’s not just one chemical, or one system, it’s many. And our body changes as well. The important thing is to help the patient consolidate their rhythms, whether through light therapy, daily exercise, cognitive behavioral therapy for insomnia, or other evidence-based interventions and their combination. The same applies for a person with dementia as for the rest of us.”

None of the investigators outside of the industry-sponsored studies had relevant disclosures.

LOS ANGELES – While a large number of older adults take prescription and nonprescription medications to help them sleep, the effect of these medications on dementia risk is unclear, with most researchers advocating a cautious and conservative approach to prescribing.

Nastasic/iStockphoto.com

Research is increasingly revealing a bidirectional relationship between sleep and dementia. Poor sleep – especially from insomnia, sleep deprivation, or obstructive sleep apnea – is known to increase dementia risk. Dementias, meanwhile, are associated with serious circadian rhythm disturbances, leading to nighttime sleep loss and increasing the likelihood of institutionalization.

At the Alzheimer’s Association International Conference, researchers presented findings assessing the links between sleep medication use and dementia and also what agents or approaches might safely improve sleep in people with sleep disorders who are at risk for dementia or who have been diagnosed with dementia.
 

Sex- and race-based differences in risk

Yue Leng, PhD, of the University of California, San Francisco, reported a link between frequent sleep medication use and later dementia – but only in white adults. Dr. Leng presented findings from the National Institutes of Health–funded Health, Aging, and Body Composition Study, which recruited 3,068 subjects aged 70-79 and followed them for 15 years. At baseline, 2.7% of African Americans and 7.7% of whites in the study reported taking sleep medications “often” or “almost always.”

Dr. Leng and her colleagues found that white subjects who reported taking sleep aids five or more times a month at baseline had a nearly 80% higher risk of developing dementia during the course of the study (hazard ratio, 1.79; 95% confidence interval, 1.21-2.66), compared with people who reported never taking sleep aids or taking them less frequently.

The researchers saw no between-sex differences for this finding, and adjusted for a variety of genetic and lifestyle confounders. Importantly, no significant increase in dementia risk was seen for black subjects, who made up more than one-third of the cohort.

Dr. Leng told the conference that the researchers could not explain why black participants did not see similarly increased dementia risk. Also, she noted, researchers did not have information on the specific sleep medications people used: benzodiazepines, antihistamines, antidepressants, or other types of drugs. Nonetheless, she told the conference, the findings ratified the cautious approach many dementia experts are already stressing.


“Do we really need to prescribe so many sleep meds to older adults who are already at risk for cognitive impairment?” Dr. Leng said, adding: “I am a big advocate of behavioral sleep interventions.” People with clinical sleep problems “should be referred to sleep centers” for a fuller assessment before medication is prescribed, she said.

Findings from another cohort study, meanwhile, suggest that there could be sex-related differences in how sleep aids affect dementia risk. Investigators at Utah State University in Logan used data from some 3,656 older adults in the Cache County Study on Memory and Aging, an NIH-backed cohort study of white adults in Utah without dementia at baseline who were followed for 12 years.

The investigators, led by doctoral student Elizabeth Vernon, found that men reporting use of sleep medication saw more than threefold higher risk of developing Alzheimer’s disease than did men who did not use sleep aids (HR, 3.604; P = .0001).

Women who did not report having sleep disturbance but used sleep-inducing medications were at nearly fourfold greater risk for developing Alzheimer’s disease (HR, 3.916; P = .0001). Women who self-reported sleep disturbances at baseline, meanwhile, saw a reduction in Alzheimer’s risk of about one-third associated with the use of sleep medications.

Ms. Vernon told the conference that, despite the finding of risk reduction for this particular group of women, caution in prescribing sleep aids was warranted.

Common sleep drugs linked to cognitive aging

Chris Fox, MD, a researcher at the University of East Anglia in Norwich, England, and his colleagues demonstrated in 2018 that long-term exposure to anticholinergic drugs, a class that includes some antidepressants and antihistamines used to promote sleep, was associated with a higher risk of dementia, while use of benzodiazepines, a class of sedatives used commonly in older people as sleep aids, was not. (Whether benzodiazepine exposure relates to dementia remains controversial.)

At AAIC 2019, Dr. Fox presented findings from a study of 337 brains in a U.K. brain bank, of which 17% and 21% came from users of benzodiazepines and anticholinergic drugs, whose usage history was well documented. Dr. Fox and his colleagues found that, while neither anticholinergic nor benzodiazepine exposure was associated with brain pathology specific to that seen in Alzheimer’s disease, both classes of drugs were associated with “slight signals in neuronal loss” in one brain region, the nucleus basalis of Meynert. Dr. Fox described the drugs as causing “an increase in cognitive aging” which could bear on Alzheimer’s risk without being directly causative.
 

Newer sleep drugs may help Alzheimer’s patients

Scientists working for drug manufacturers presented findings on agents to counter the circadian rhythm disturbances seen in people with Alzheimer’s disease. Margaret Moline, PhD, of Eisai in Woodcliff Lake, N.J., showed some results from a phase 2, dose-ranging, placebo-controlled study of the experimental agent lemborexant in 62 subjects aged 60-90 with mild to moderate Alzheimer’s disease and sleep disturbances. (Lemborexant, an orexin receptor agonist that acts to regulate wakefulness, is being investigated in a broad range of sleep disorders.) Patients were randomized to one of four doses of lemborexant or placebo and wore a device for sleep monitoring. Nighttime activity indicating arousal was significantly lower for people in two dosage arms, 5 mg and 10 mg, compared with placebo, and treatment groups saw trends toward less sleep fragmentation and higher total sleep time, Dr. Moline told the conference.

Suvorexant (Belsomra), the only orexin receptor antagonist currently licensed as a sleep aid, is also being tested in people with Alzheimer’s disease. At AAIC 2019, Joseph Herring, MD, PhD, of Merck in Kenilworth, N.J., presented results from a placebo-controlled trial of 277 patients with Alzheimer’s disease and insomnia, and reported that treatment with 10 or 20 mg of suvorexant over 4 weeks was associated with about an extra half hour of total nightly sleep, with a 73-minute mean increase from baseline, compared with 45 minutes for patients receiving placebo (95% CI, 11-45; P less than .005).
 

Trazodone linked to slower cognitive decline

An inexpensive antidepressant used in low doses as a sleep aid, including in people with Alzheimer’s disease, was associated with a delay in cognitive decline in older adults, according to results from a retrospective study. Elissaios Karageorgiou, MD, PhD, of the University of California, San Francisco, and the Neurological Institute of Athens presented results derived from two cohorts: patients enrolled at the UCSF Memory and Aging Center and women enrolled in the Study for Osteoporotic Fractures (SOF) in Women. The investigators were able to identify trazodone users in the studies (with two or more contiguous study visits reporting trazodone use) and match them with control patients from the same cohorts who did not use trazodone.

Trazodone was studied because previous research suggests it increases total sleep time in patients with Alzheimer’s disease without affecting next-day cognitive performance.

Trazodone-using patients in the UCSF cohort (n = 25) saw significantly less decline in Mini Mental State Exam (MMSE) scores over 4 years, compared with nonusers (0.27 vs. 0.70 points per year; P = .023), an effect that remained statistically significant even after adjusting for sedative and stimulant use and the expected progression of Alzheimer’s disease pathology. Importantly, the slower decline was seen only among subjects with sleep complaints at baseline and especially those whose sleep improved over time, suggesting that the cognitive benefit was mediated by improved sleep.

In the SOF cohort of 46 trazodone users matched with 148 nonusers, no significant protective or negative effect related to long-term trazodone use was found using the MMSE or the Trails Making Test. In this analysis, however, baseline and longitudinal sleep quality was not captured in the group-matching process, neither was the use of other medications. The patient group was slightly older, and all patients were women.

Dr. Karageorgiou said in an interview that the link between improved sleep, trazodone, and cognition needs to be validated in prospective intervention studies. Trazodone, he said, appears to work best in people with a specific type of insomnia characterized by cortical and behavioral hyperarousal, and its cognitive effect appears limited to people whose sleep improves with treatment. “You’re not going to see long-term cognitive benefits if it’s not improving your sleep,” Dr. Karageorgiou said. “So, whether trazodone improves sleep or not in a patient after a few months can be an early indicator for the clinician to continue using it or suspend it, because it is unlikely to help their cognition otherwise.”

He stressed that physicians need to be broadly focused on improving sleep to help patients with, or at risk for, dementia by consolidating their sleep rhythms.

“Trazodone is not the magic bullet, and I don’t think we will ever have a magic bullet,” Dr. Karageorgiou said. “Because when our brain degenerates, it’s not just one chemical, or one system, it’s many. And our body changes as well. The important thing is to help the patient consolidate their rhythms, whether through light therapy, daily exercise, cognitive behavioral therapy for insomnia, or other evidence-based interventions and their combination. The same applies for a person with dementia as for the rest of us.”

None of the investigators outside of the industry-sponsored studies had relevant disclosures.

LOS ANGELES – While a large number of older adults take prescription and nonprescription medications to help them sleep, the effect of these medications on dementia risk is unclear, with most researchers advocating a cautious and conservative approach to prescribing.

Nastasic/iStockphoto.com

Research is increasingly revealing a bidirectional relationship between sleep and dementia. Poor sleep – especially from insomnia, sleep deprivation, or obstructive sleep apnea – is known to increase dementia risk. Dementias, meanwhile, are associated with serious circadian rhythm disturbances, leading to nighttime sleep loss and increasing the likelihood of institutionalization.

At the Alzheimer’s Association International Conference, researchers presented findings assessing the links between sleep medication use and dementia and also what agents or approaches might safely improve sleep in people with sleep disorders who are at risk for dementia or who have been diagnosed with dementia.
 

Sex- and race-based differences in risk

Yue Leng, PhD, of the University of California, San Francisco, reported a link between frequent sleep medication use and later dementia – but only in white adults. Dr. Leng presented findings from the National Institutes of Health–funded Health, Aging, and Body Composition Study, which recruited 3,068 subjects aged 70-79 and followed them for 15 years. At baseline, 2.7% of African Americans and 7.7% of whites in the study reported taking sleep medications “often” or “almost always.”

Dr. Leng and her colleagues found that white subjects who reported taking sleep aids five or more times a month at baseline had a nearly 80% higher risk of developing dementia during the course of the study (hazard ratio, 1.79; 95% confidence interval, 1.21-2.66), compared with people who reported never taking sleep aids or taking them less frequently.

The researchers saw no between-sex differences for this finding, and adjusted for a variety of genetic and lifestyle confounders. Importantly, no significant increase in dementia risk was seen for black subjects, who made up more than one-third of the cohort.

Dr. Leng told the conference that the researchers could not explain why black participants did not see similarly increased dementia risk. Also, she noted, researchers did not have information on the specific sleep medications people used: benzodiazepines, antihistamines, antidepressants, or other types of drugs. Nonetheless, she told the conference, the findings ratified the cautious approach many dementia experts are already stressing.


“Do we really need to prescribe so many sleep meds to older adults who are already at risk for cognitive impairment?” Dr. Leng said, adding: “I am a big advocate of behavioral sleep interventions.” People with clinical sleep problems “should be referred to sleep centers” for a fuller assessment before medication is prescribed, she said.

Findings from another cohort study, meanwhile, suggest that there could be sex-related differences in how sleep aids affect dementia risk. Investigators at Utah State University in Logan used data from some 3,656 older adults in the Cache County Study on Memory and Aging, an NIH-backed cohort study of white adults in Utah without dementia at baseline who were followed for 12 years.

The investigators, led by doctoral student Elizabeth Vernon, found that men reporting use of sleep medication saw more than threefold higher risk of developing Alzheimer’s disease than did men who did not use sleep aids (HR, 3.604; P = .0001).

Women who did not report having sleep disturbance but used sleep-inducing medications were at nearly fourfold greater risk for developing Alzheimer’s disease (HR, 3.916; P = .0001). Women who self-reported sleep disturbances at baseline, meanwhile, saw a reduction in Alzheimer’s risk of about one-third associated with the use of sleep medications.

Ms. Vernon told the conference that, despite the finding of risk reduction for this particular group of women, caution in prescribing sleep aids was warranted.

Common sleep drugs linked to cognitive aging

Chris Fox, MD, a researcher at the University of East Anglia in Norwich, England, and his colleagues demonstrated in 2018 that long-term exposure to anticholinergic drugs, a class that includes some antidepressants and antihistamines used to promote sleep, was associated with a higher risk of dementia, while use of benzodiazepines, a class of sedatives used commonly in older people as sleep aids, was not. (Whether benzodiazepine exposure relates to dementia remains controversial.)

At AAIC 2019, Dr. Fox presented findings from a study of 337 brains in a U.K. brain bank, of which 17% and 21% came from users of benzodiazepines and anticholinergic drugs, whose usage history was well documented. Dr. Fox and his colleagues found that, while neither anticholinergic nor benzodiazepine exposure was associated with brain pathology specific to that seen in Alzheimer’s disease, both classes of drugs were associated with “slight signals in neuronal loss” in one brain region, the nucleus basalis of Meynert. Dr. Fox described the drugs as causing “an increase in cognitive aging” which could bear on Alzheimer’s risk without being directly causative.
 

Newer sleep drugs may help Alzheimer’s patients

Scientists working for drug manufacturers presented findings on agents to counter the circadian rhythm disturbances seen in people with Alzheimer’s disease. Margaret Moline, PhD, of Eisai in Woodcliff Lake, N.J., showed some results from a phase 2, dose-ranging, placebo-controlled study of the experimental agent lemborexant in 62 subjects aged 60-90 with mild to moderate Alzheimer’s disease and sleep disturbances. (Lemborexant, an orexin receptor agonist that acts to regulate wakefulness, is being investigated in a broad range of sleep disorders.) Patients were randomized to one of four doses of lemborexant or placebo and wore a device for sleep monitoring. Nighttime activity indicating arousal was significantly lower for people in two dosage arms, 5 mg and 10 mg, compared with placebo, and treatment groups saw trends toward less sleep fragmentation and higher total sleep time, Dr. Moline told the conference.

Suvorexant (Belsomra), the only orexin receptor antagonist currently licensed as a sleep aid, is also being tested in people with Alzheimer’s disease. At AAIC 2019, Joseph Herring, MD, PhD, of Merck in Kenilworth, N.J., presented results from a placebo-controlled trial of 277 patients with Alzheimer’s disease and insomnia, and reported that treatment with 10 or 20 mg of suvorexant over 4 weeks was associated with about an extra half hour of total nightly sleep, with a 73-minute mean increase from baseline, compared with 45 minutes for patients receiving placebo (95% CI, 11-45; P less than .005).
 

Trazodone linked to slower cognitive decline

An inexpensive antidepressant used in low doses as a sleep aid, including in people with Alzheimer’s disease, was associated with a delay in cognitive decline in older adults, according to results from a retrospective study. Elissaios Karageorgiou, MD, PhD, of the University of California, San Francisco, and the Neurological Institute of Athens presented results derived from two cohorts: patients enrolled at the UCSF Memory and Aging Center and women enrolled in the Study for Osteoporotic Fractures (SOF) in Women. The investigators were able to identify trazodone users in the studies (with two or more contiguous study visits reporting trazodone use) and match them with control patients from the same cohorts who did not use trazodone.

Trazodone was studied because previous research suggests it increases total sleep time in patients with Alzheimer’s disease without affecting next-day cognitive performance.

Trazodone-using patients in the UCSF cohort (n = 25) saw significantly less decline in Mini Mental State Exam (MMSE) scores over 4 years, compared with nonusers (0.27 vs. 0.70 points per year; P = .023), an effect that remained statistically significant even after adjusting for sedative and stimulant use and the expected progression of Alzheimer’s disease pathology. Importantly, the slower decline was seen only among subjects with sleep complaints at baseline and especially those whose sleep improved over time, suggesting that the cognitive benefit was mediated by improved sleep.

In the SOF cohort of 46 trazodone users matched with 148 nonusers, no significant protective or negative effect related to long-term trazodone use was found using the MMSE or the Trails Making Test. In this analysis, however, baseline and longitudinal sleep quality was not captured in the group-matching process, neither was the use of other medications. The patient group was slightly older, and all patients were women.

Dr. Karageorgiou said in an interview that the link between improved sleep, trazodone, and cognition needs to be validated in prospective intervention studies. Trazodone, he said, appears to work best in people with a specific type of insomnia characterized by cortical and behavioral hyperarousal, and its cognitive effect appears limited to people whose sleep improves with treatment. “You’re not going to see long-term cognitive benefits if it’s not improving your sleep,” Dr. Karageorgiou said. “So, whether trazodone improves sleep or not in a patient after a few months can be an early indicator for the clinician to continue using it or suspend it, because it is unlikely to help their cognition otherwise.”

He stressed that physicians need to be broadly focused on improving sleep to help patients with, or at risk for, dementia by consolidating their sleep rhythms.

“Trazodone is not the magic bullet, and I don’t think we will ever have a magic bullet,” Dr. Karageorgiou said. “Because when our brain degenerates, it’s not just one chemical, or one system, it’s many. And our body changes as well. The important thing is to help the patient consolidate their rhythms, whether through light therapy, daily exercise, cognitive behavioral therapy for insomnia, or other evidence-based interventions and their combination. The same applies for a person with dementia as for the rest of us.”

None of the investigators outside of the industry-sponsored studies had relevant disclosures.

LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.

Michele G. Sullivan/MDedge News

The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.

“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”

The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.

Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.

The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.

At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.

At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.

“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”

Dr. Jeon had no financial declarations.

[email protected]

SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.

LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.

Michele G. Sullivan/MDedge News

The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.

“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”

The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.

Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.

The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.

At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.

At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.

“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”

Dr. Jeon had no financial declarations.

[email protected]

SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.

LOS ANGELES – Dysregulated sleep-wake cycles may be linked to cerebral glucose hypometabolism and subtle cognitive changes, both of which are early signs of Alzheimer’s disease–like neurodegeneration, according to a 2-year study of older Korean adults.

Michele G. Sullivan/MDedge News

The association was particularly strong in subjects who experienced delayed acrophase, the peak of the normal sleep-wake cycle, So-Yeon Jeon, MD, said at the Alzheimer’s Association International Conference. It’s not yet clear whether the changes are a risk factor for dementia or a prodromal sign of neurodegeneration, but even without full elucidation, the findings could have value as a signal of impending neurodegeneration, said Dr. Jeon of Seoul (South Korea) National University.

“Our findings suggest that delayed acrophase may be used as a predictor for the progression of Alzheimer’s-type neurodegeneration and cognitive decline in the near future in old individuals with diverse cognitive status,” she said. “But the relationship between circadian phases and neurodegeneration is complex and not yet well understood.”

The 24-month study comprised 215 elderly adults enrolled in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). They were a mean of 70 years old at baseline; 143 were cognitively normal, 40 had mild cognitive impairment, and 32 had Alzheimer’s dementia. Both at baseline and 2 years, everyone underwent a comprehensive neuropsychological assessment, amyloid PET brain imaging with Pittsburgh compound B, and an [18F]-fluorodeoxyglucose PET scan to determine brain glucose metabolic rate.

Before each assessment, the investigators measured sleep and circadian rhythms with 8 days of actigraphy. This assessed sleep variables (total sleep time, sleep latency, sleep efficiency, and wakefulness after sleep); rest-activity rhythm variables (midline estimated statistic of rhythm, amplitude, and acrophase), and some nonparametric values including interdaily stability, intradaily variability, and relative amplitude of sleep cycles. Subjects also completed sleep diaries during these periods.

The study’s main outcomes were 2-year changes in the Mini Mental State Exam (MMSE) score and in Alzheimer’s imaging biomarkers, including glucose metabolism and amyloid deposition. All analyses controlled for age, sex, Clinical Dementia Rating score, apolipoprotein E allele status, and baseline cognition.

At baseline, lower total sleep time was significantly associated with hypometabolism in areas associated with Alzheimer’s pathology as well as lower mean MMSE scores. Circadian variables showed no significant associations with these characteristics. However, the relative amplitude of circadian rhythm was significantly associated with hypometabolism and with lower MMSE score. There were no associations with brain amyloid load.

At 2 years, acrophase was associated with declines in cerebral glucose metabolism and further changes in the MMSE, even after the researchers controlled for the potential confounders. Delayed acrophase, although not associated with either metabolic rate or cognition at baseline, did significantly influence both at 2 years, suggesting a rapidly eroding clinical picture.

“Neurodegeneration over 2 years means the disease is progressing rapidly and subjects are likely to have tauopathies or other proteinopathy,” Dr. Jeon said. “These pathologies may either be resulting in delayed acrophase followed by neurodegeneration, or they may be prodromal symptoms of impending neurodegeneration. Whether they are early symptoms or early risk factors is not currently known, however. Two years is too short of a follow-up to determine these questions.”

Dr. Jeon had no financial declarations.

[email protected]

SOURCE: Jeon SY et al. AAIC 2019, abstract 33543.

Restless legs syndrome (RLS) is a very common disease affecting about 10% of Caucasian adults with about one third of them having RLS symptoms severe enough to require treatment.

Although many patients still go undiagnosed or misdiagnosed, the diagnosis is easily established with the five diagnostic criteria that are simplified by the acronym URGES:

1. Urge to move the legs associated with unpleasant leg sensations.

2. Rest induces symptoms.

3. Gets better with activity.

4. Evening and nighttime worsening.

5. Solely not accounted by another medical or behavioral condition.

The diagnosis is based completely upon the history. However, supplemental tests can be helpful to rule out underlying conditions that increase the risk of RLS. Routine lab tests, such as serum creatinine (to rule out renal disease), TSH (to rule out thyroid disease), and a CBC/ferritin/iron with transferrin saturation (to rule out low iron stores) should be ordered if not done recently.

A polysomnographic sleep study should not be ordered unless there is a strong suspicion that sleep apnea is present. Even very frequent PLM (periodic limb movements) are not that helpful in confirming the diagnosis of RLS since they are nonspecific and often occurring with drug treatment (SSRIs, SNRIs) and many medical conditions such as sleep apnea, narcolepsy, and REM behavior disorder.

The paradigm for treating RLS has been presented in the consensus article published in 2013 (Silber MH, et al. Mayo Clin Proc. 2013 Sep;88[9]:977). Since 2013, there has been a gradual shift of that paradigm that recommended starting an approved dopamine agonist (pramipexole, ropinirole, or rotigotine) or an alpha-2-delta ligand (gabapentin enacarbil, gabapentin, or pregabalin) as first-line treatment. Although dopamine agonists provide excellent relief of RLS symptoms initially, with time, they tend to markedly worsen RLS. This process is called RLS augmentation and has become one of the most common causes of refractory RLS and difficult-to-treat patients.

RLS augmentation typically onsets a few months to several years after starting a short-acting dopamine agonist (DA) like pramipexole or ropinirole. It presents with symptoms occurring a few hours earlier than prior to starting the medication, symptoms becoming more intense with less rest time needed to trigger RLS symptoms, drugs becoming less effective both in effectiveness and duration of action, and spread of symptoms to other body parts (arms, trunk, and even head). The majority of physicians mistake this worsening of RLS for the natural progression of the disease and, thus, increase the dose of the DA, which provides temporary improvement. Further increases become progressively necessary until the patient is receiving very large doses, often exceeding 10 times the FDA maximum recommended doses. Eventually, further dose increments provide minimal additional benefit, leaving patients with severe, around the clock RLS symptoms causing extreme misery. To be more aware of augmentation, physicians should consider augmentation may be occurring whenever a patient who has been on a regimen of stable dopamine agonist treatment for at least 6 months requests more medication.

Dr. Buchfuhrer is with Stanford University, Department of Psychiatry and Behavioral Sciences in the School of Medicine, Division of Sleep Medicine, Stanford, Calif.

Restless legs syndrome (RLS) is a very common disease affecting about 10% of Caucasian adults with about one third of them having RLS symptoms severe enough to require treatment.

Although many patients still go undiagnosed or misdiagnosed, the diagnosis is easily established with the five diagnostic criteria that are simplified by the acronym URGES:

1. Urge to move the legs associated with unpleasant leg sensations.

2. Rest induces symptoms.

3. Gets better with activity.

4. Evening and nighttime worsening.

5. Solely not accounted by another medical or behavioral condition.

The diagnosis is based completely upon the history. However, supplemental tests can be helpful to rule out underlying conditions that increase the risk of RLS. Routine lab tests, such as serum creatinine (to rule out renal disease), TSH (to rule out thyroid disease), and a CBC/ferritin/iron with transferrin saturation (to rule out low iron stores) should be ordered if not done recently.

A polysomnographic sleep study should not be ordered unless there is a strong suspicion that sleep apnea is present. Even very frequent PLM (periodic limb movements) are not that helpful in confirming the diagnosis of RLS since they are nonspecific and often occurring with drug treatment (SSRIs, SNRIs) and many medical conditions such as sleep apnea, narcolepsy, and REM behavior disorder.

The paradigm for treating RLS has been presented in the consensus article published in 2013 (Silber MH, et al. Mayo Clin Proc. 2013 Sep;88[9]:977). Since 2013, there has been a gradual shift of that paradigm that recommended starting an approved dopamine agonist (pramipexole, ropinirole, or rotigotine) or an alpha-2-delta ligand (gabapentin enacarbil, gabapentin, or pregabalin) as first-line treatment. Although dopamine agonists provide excellent relief of RLS symptoms initially, with time, they tend to markedly worsen RLS. This process is called RLS augmentation and has become one of the most common causes of refractory RLS and difficult-to-treat patients.

RLS augmentation typically onsets a few months to several years after starting a short-acting dopamine agonist (DA) like pramipexole or ropinirole. It presents with symptoms occurring a few hours earlier than prior to starting the medication, symptoms becoming more intense with less rest time needed to trigger RLS symptoms, drugs becoming less effective both in effectiveness and duration of action, and spread of symptoms to other body parts (arms, trunk, and even head). The majority of physicians mistake this worsening of RLS for the natural progression of the disease and, thus, increase the dose of the DA, which provides temporary improvement. Further increases become progressively necessary until the patient is receiving very large doses, often exceeding 10 times the FDA maximum recommended doses. Eventually, further dose increments provide minimal additional benefit, leaving patients with severe, around the clock RLS symptoms causing extreme misery. To be more aware of augmentation, physicians should consider augmentation may be occurring whenever a patient who has been on a regimen of stable dopamine agonist treatment for at least 6 months requests more medication.

Dr. Buchfuhrer is with Stanford University, Department of Psychiatry and Behavioral Sciences in the School of Medicine, Division of Sleep Medicine, Stanford, Calif.

Restless legs syndrome (RLS) is a very common disease affecting about 10% of Caucasian adults with about one third of them having RLS symptoms severe enough to require treatment.

Although many patients still go undiagnosed or misdiagnosed, the diagnosis is easily established with the five diagnostic criteria that are simplified by the acronym URGES:

1. Urge to move the legs associated with unpleasant leg sensations.

2. Rest induces symptoms.

3. Gets better with activity.

4. Evening and nighttime worsening.

5. Solely not accounted by another medical or behavioral condition.

The diagnosis is based completely upon the history. However, supplemental tests can be helpful to rule out underlying conditions that increase the risk of RLS. Routine lab tests, such as serum creatinine (to rule out renal disease), TSH (to rule out thyroid disease), and a CBC/ferritin/iron with transferrin saturation (to rule out low iron stores) should be ordered if not done recently.

A polysomnographic sleep study should not be ordered unless there is a strong suspicion that sleep apnea is present. Even very frequent PLM (periodic limb movements) are not that helpful in confirming the diagnosis of RLS since they are nonspecific and often occurring with drug treatment (SSRIs, SNRIs) and many medical conditions such as sleep apnea, narcolepsy, and REM behavior disorder.

The paradigm for treating RLS has been presented in the consensus article published in 2013 (Silber MH, et al. Mayo Clin Proc. 2013 Sep;88[9]:977). Since 2013, there has been a gradual shift of that paradigm that recommended starting an approved dopamine agonist (pramipexole, ropinirole, or rotigotine) or an alpha-2-delta ligand (gabapentin enacarbil, gabapentin, or pregabalin) as first-line treatment. Although dopamine agonists provide excellent relief of RLS symptoms initially, with time, they tend to markedly worsen RLS. This process is called RLS augmentation and has become one of the most common causes of refractory RLS and difficult-to-treat patients.

RLS augmentation typically onsets a few months to several years after starting a short-acting dopamine agonist (DA) like pramipexole or ropinirole. It presents with symptoms occurring a few hours earlier than prior to starting the medication, symptoms becoming more intense with less rest time needed to trigger RLS symptoms, drugs becoming less effective both in effectiveness and duration of action, and spread of symptoms to other body parts (arms, trunk, and even head). The majority of physicians mistake this worsening of RLS for the natural progression of the disease and, thus, increase the dose of the DA, which provides temporary improvement. Further increases become progressively necessary until the patient is receiving very large doses, often exceeding 10 times the FDA maximum recommended doses. Eventually, further dose increments provide minimal additional benefit, leaving patients with severe, around the clock RLS symptoms causing extreme misery. To be more aware of augmentation, physicians should consider augmentation may be occurring whenever a patient who has been on a regimen of stable dopamine agonist treatment for at least 6 months requests more medication.

Dr. Buchfuhrer is with Stanford University, Department of Psychiatry and Behavioral Sciences in the School of Medicine, Division of Sleep Medicine, Stanford, Calif.

SAN ANTONIO – Continuous positive airway pressure (CPAP) adherence varies by age, sex, and date of setup, results from an analysis of national data showed.

Courtesy Dr. Krishna Sundar

However, whether the sources of variability stem from patient factors such as disease severity and socioeconomic status, provider factors, environmental factors, or selection biases in those who are diagnosed with obstructive sleep apnea and treated with CPAP remains to be understood, lead study author Sanjay R. Patel, MD, said at the annual meeting of the Associated Professional Sleep Societies.

In 2015, the American Academy of Sleep Medicine (AASM) endorsed CPAP adherence as a process measure, and the Centers for Medicare and Medicaid Services has used CPAP adherence as an outcome measure to limit long-term coverage of the therapy. It defines CPAP adherence as 4 or more hours of use on greater than 70% of nights in a consecutive 30-day period within the first 90 days. “Strengths of CPAP adherence as an outcome measure include the fact that it is easy to measure and it predicts improvement in sleepiness, quality of life, and blood pressure control,” said Dr. Patel, who directs the University of Pittsburgh’s Center for Sleep and Cardiovascular Outcomes Research. “One issue as to whether we should use CPAP adherence as an outcome-based quality of care measure is, does variability reflect performance at the provider and/or health care system?”

In an effort to describe CPAP adherence rates in general clinical practice as well as sources of variability, Dr. Patel and colleagues evaluated telemonitoring data maintained by Philips Respironics. The study population consisted of 714,270 patients initiated on CPAP therapy between November 2015 and August 2018 who had at least one usage session of CPAP or APAP.

Overall, 90-day adherence to CPAP was 72.5%. Age, sex, and state of residence were all significantly associated with adherence rates (P less than .05). Specifically, adherence rates ranged from 54.8% among those 18-30 years of age to 79.1% among those 61-70 years of age. “There was a plateauing of adherence rates among those in their 70s, and men tended to have a higher adherence level than women across all age groups (73.3% vs. 71.4%, respectively),” he said. “Also, people who got started on CPAP in January had a higher level of adherence than people who got started in May. The differences are relatively small compared to the large age differences, but there was a consistent trend.”


When the researchers carried out age- and sex-adjusted analyses, they observed that adherence rates were lowest in the Northeast and Southwest and highest in the Upper Midwest and Mountain West. Adherence rates ranged from 50.8% in the District of Columbia and 60.5% in New York up to 81.2% in Idaho and 81.9% in South Dakota.

“The question is, is this variability explained by quality measures?” Dr. Patel asked. “We tried to answer this question by seeing whether the variability in adherence by location correlated with other metrics of health care quality.” To accomplish this, they used Dartmouth Atlas, a project that uses Medicare data to understand drivers of health care spending and quality. To understand geographic variability in CPAP adherence, they mapped ZIP codes onto hospital referral regions (HRRs), which are regional health care markets for tertiary medical care. Each HRR has at least one hospital that performs major cardiovascular procedures and neurosurgery. ZIP codes were mapped to 306 HRRs where the majority of residents get their tertiary care.

The researchers observed that Medicare enrollees who saw a primary care physician in the past 12 months had higher rates of adherence, compared with those who did not. “Twenty-three percent of the variance in CPAP adherence across the country can be explained by this measure of having a primary care doctor,” Dr. Patel said. In addition, patients who received care from HRRs located in the middle of the United States had high adherence rates. Top performers were facilities located in Madison, Wis.; Wausau, Wis.; Dubuque, Iowa; and Bloomington, Ill. Poor performers included facilities located in the boroughs of Manhattan and the Bronx, in New York; Muskegon, Mich.; Miami; and Buffalo, N.Y.

“Some of the geographical variability may be due to patient factors such as race, income, and education level,” Dr. Patel said. “That will need to be appropriately addressed in developing a quality of care measure. Nevertheless, some of the geographic variability appears to be related to health care system and provider factors. This variability could be potentially reduced through implementation of a CPAP adherence quality outcome measure.”

Dr. Patel disclosed that he has received grant/research support from Bayer Pharmaceuticals and Philips Respironics, and has served as a consultant to the American Academy of Sleep Medicine.

[email protected]

SOURCE: Patel SR et al. SLEEP 2019, Abstract 0513.

SAN ANTONIO – Continuous positive airway pressure (CPAP) adherence varies by age, sex, and date of setup, results from an analysis of national data showed.

Courtesy Dr. Krishna Sundar

However, whether the sources of variability stem from patient factors such as disease severity and socioeconomic status, provider factors, environmental factors, or selection biases in those who are diagnosed with obstructive sleep apnea and treated with CPAP remains to be understood, lead study author Sanjay R. Patel, MD, said at the annual meeting of the Associated Professional Sleep Societies.

In 2015, the American Academy of Sleep Medicine (AASM) endorsed CPAP adherence as a process measure, and the Centers for Medicare and Medicaid Services has used CPAP adherence as an outcome measure to limit long-term coverage of the therapy. It defines CPAP adherence as 4 or more hours of use on greater than 70% of nights in a consecutive 30-day period within the first 90 days. “Strengths of CPAP adherence as an outcome measure include the fact that it is easy to measure and it predicts improvement in sleepiness, quality of life, and blood pressure control,” said Dr. Patel, who directs the University of Pittsburgh’s Center for Sleep and Cardiovascular Outcomes Research. “One issue as to whether we should use CPAP adherence as an outcome-based quality of care measure is, does variability reflect performance at the provider and/or health care system?”

In an effort to describe CPAP adherence rates in general clinical practice as well as sources of variability, Dr. Patel and colleagues evaluated telemonitoring data maintained by Philips Respironics. The study population consisted of 714,270 patients initiated on CPAP therapy between November 2015 and August 2018 who had at least one usage session of CPAP or APAP.

Overall, 90-day adherence to CPAP was 72.5%. Age, sex, and state of residence were all significantly associated with adherence rates (P less than .05). Specifically, adherence rates ranged from 54.8% among those 18-30 years of age to 79.1% among those 61-70 years of age. “There was a plateauing of adherence rates among those in their 70s, and men tended to have a higher adherence level than women across all age groups (73.3% vs. 71.4%, respectively),” he said. “Also, people who got started on CPAP in January had a higher level of adherence than people who got started in May. The differences are relatively small compared to the large age differences, but there was a consistent trend.”


When the researchers carried out age- and sex-adjusted analyses, they observed that adherence rates were lowest in the Northeast and Southwest and highest in the Upper Midwest and Mountain West. Adherence rates ranged from 50.8% in the District of Columbia and 60.5% in New York up to 81.2% in Idaho and 81.9% in South Dakota.

“The question is, is this variability explained by quality measures?” Dr. Patel asked. “We tried to answer this question by seeing whether the variability in adherence by location correlated with other metrics of health care quality.” To accomplish this, they used Dartmouth Atlas, a project that uses Medicare data to understand drivers of health care spending and quality. To understand geographic variability in CPAP adherence, they mapped ZIP codes onto hospital referral regions (HRRs), which are regional health care markets for tertiary medical care. Each HRR has at least one hospital that performs major cardiovascular procedures and neurosurgery. ZIP codes were mapped to 306 HRRs where the majority of residents get their tertiary care.

The researchers observed that Medicare enrollees who saw a primary care physician in the past 12 months had higher rates of adherence, compared with those who did not. “Twenty-three percent of the variance in CPAP adherence across the country can be explained by this measure of having a primary care doctor,” Dr. Patel said. In addition, patients who received care from HRRs located in the middle of the United States had high adherence rates. Top performers were facilities located in Madison, Wis.; Wausau, Wis.; Dubuque, Iowa; and Bloomington, Ill. Poor performers included facilities located in the boroughs of Manhattan and the Bronx, in New York; Muskegon, Mich.; Miami; and Buffalo, N.Y.

“Some of the geographical variability may be due to patient factors such as race, income, and education level,” Dr. Patel said. “That will need to be appropriately addressed in developing a quality of care measure. Nevertheless, some of the geographic variability appears to be related to health care system and provider factors. This variability could be potentially reduced through implementation of a CPAP adherence quality outcome measure.”

Dr. Patel disclosed that he has received grant/research support from Bayer Pharmaceuticals and Philips Respironics, and has served as a consultant to the American Academy of Sleep Medicine.

[email protected]

SOURCE: Patel SR et al. SLEEP 2019, Abstract 0513.

SAN ANTONIO – Continuous positive airway pressure (CPAP) adherence varies by age, sex, and date of setup, results from an analysis of national data showed.

Courtesy Dr. Krishna Sundar

However, whether the sources of variability stem from patient factors such as disease severity and socioeconomic status, provider factors, environmental factors, or selection biases in those who are diagnosed with obstructive sleep apnea and treated with CPAP remains to be understood, lead study author Sanjay R. Patel, MD, said at the annual meeting of the Associated Professional Sleep Societies.

In 2015, the American Academy of Sleep Medicine (AASM) endorsed CPAP adherence as a process measure, and the Centers for Medicare and Medicaid Services has used CPAP adherence as an outcome measure to limit long-term coverage of the therapy. It defines CPAP adherence as 4 or more hours of use on greater than 70% of nights in a consecutive 30-day period within the first 90 days. “Strengths of CPAP adherence as an outcome measure include the fact that it is easy to measure and it predicts improvement in sleepiness, quality of life, and blood pressure control,” said Dr. Patel, who directs the University of Pittsburgh’s Center for Sleep and Cardiovascular Outcomes Research. “One issue as to whether we should use CPAP adherence as an outcome-based quality of care measure is, does variability reflect performance at the provider and/or health care system?”

In an effort to describe CPAP adherence rates in general clinical practice as well as sources of variability, Dr. Patel and colleagues evaluated telemonitoring data maintained by Philips Respironics. The study population consisted of 714,270 patients initiated on CPAP therapy between November 2015 and August 2018 who had at least one usage session of CPAP or APAP.

Overall, 90-day adherence to CPAP was 72.5%. Age, sex, and state of residence were all significantly associated with adherence rates (P less than .05). Specifically, adherence rates ranged from 54.8% among those 18-30 years of age to 79.1% among those 61-70 years of age. “There was a plateauing of adherence rates among those in their 70s, and men tended to have a higher adherence level than women across all age groups (73.3% vs. 71.4%, respectively),” he said. “Also, people who got started on CPAP in January had a higher level of adherence than people who got started in May. The differences are relatively small compared to the large age differences, but there was a consistent trend.”


When the researchers carried out age- and sex-adjusted analyses, they observed that adherence rates were lowest in the Northeast and Southwest and highest in the Upper Midwest and Mountain West. Adherence rates ranged from 50.8% in the District of Columbia and 60.5% in New York up to 81.2% in Idaho and 81.9% in South Dakota.

“The question is, is this variability explained by quality measures?” Dr. Patel asked. “We tried to answer this question by seeing whether the variability in adherence by location correlated with other metrics of health care quality.” To accomplish this, they used Dartmouth Atlas, a project that uses Medicare data to understand drivers of health care spending and quality. To understand geographic variability in CPAP adherence, they mapped ZIP codes onto hospital referral regions (HRRs), which are regional health care markets for tertiary medical care. Each HRR has at least one hospital that performs major cardiovascular procedures and neurosurgery. ZIP codes were mapped to 306 HRRs where the majority of residents get their tertiary care.

The researchers observed that Medicare enrollees who saw a primary care physician in the past 12 months had higher rates of adherence, compared with those who did not. “Twenty-three percent of the variance in CPAP adherence across the country can be explained by this measure of having a primary care doctor,” Dr. Patel said. In addition, patients who received care from HRRs located in the middle of the United States had high adherence rates. Top performers were facilities located in Madison, Wis.; Wausau, Wis.; Dubuque, Iowa; and Bloomington, Ill. Poor performers included facilities located in the boroughs of Manhattan and the Bronx, in New York; Muskegon, Mich.; Miami; and Buffalo, N.Y.

“Some of the geographical variability may be due to patient factors such as race, income, and education level,” Dr. Patel said. “That will need to be appropriately addressed in developing a quality of care measure. Nevertheless, some of the geographic variability appears to be related to health care system and provider factors. This variability could be potentially reduced through implementation of a CPAP adherence quality outcome measure.”

Dr. Patel disclosed that he has received grant/research support from Bayer Pharmaceuticals and Philips Respironics, and has served as a consultant to the American Academy of Sleep Medicine.

[email protected]

SOURCE: Patel SR et al. SLEEP 2019, Abstract 0513.

SAN DIEGO – The prevalence of obstructive sleep apnea (OSA) is substantially lower using the Centers for Medicare & Medicaid Services apnea-hypopnea index definition of OSA than using the one recommended by the American Academy of Sleep Medicine.

Doug Brunk/MDedge News

In addition, among individuals who did not have OSA using the CMS definition but met criteria using the AASM definition of OSA, an apnea-hypopnea index (AHI) of five events or greater per hour was associated with a greater likelihood of having hypertension.

The findings come from an analysis which set out to assess the relationship between OSA and hypertension using the AASM-recommended definition and the 2018 American Heart Association/American College of Cardiology blood pressure guidelines, and to determine if there is an association between hypertension and OSA among individuals who did not meet the CMS definition of OSA.

“Given the substantial morbidity associated with hypertension, these results suggest that universal adoption of the AASM AHI definition would be a reasonable step in ensuring appropriate diagnosis and treatment of OSA,” lead study author Stuart F. Quan, MD, said at the annual meeting of the Associated Professional Sleep Societies.

Dr. Quan, of the division of sleep and circadian disorders at Brigham and Women’s Hospital in Boston, noted that a number of studies have demonstrated that OSA is a risk factor for hypertension and a variety of other medical conditions. “Rightly or wrongly, the most important metric for determining whether OSA is present and determining its severity, is the apnea-hypopnea index,” he said. “It’s the most common metric used for determining OSA severity, and mostly importantly, Medicare and some other insurers use this metric to determine whether a person is eligible for treatment. If a person falls above the line, they can get continuous positive airway pressure, for example. If they’re below the line, that’s too bad; they don’t have OSA insofar as the insurance company is concerned.”

There is no controversy as to what constitutes apnea, he continued, but some disagreement exists on the definition of hypopnea. The AASM recommends using a 3% oxygen desaturation or an arousal, while Medicare uses a definition of hypopnea requiring only a 4% oxygen desaturation. Hypertension definitions have changed recently as well. Before 2018, the definition of hypertension was greater than 140/90 mm Hg for people younger than age 65 years and 150/80 mm Hg for people age 65 years and older. In 2018, the AHA and ACC changed the hypertension guidelines, defining normal as less than 120/80 mm Hg.

“Previous studies linking OSA and hypertension used older definitions, but to my knowledge there are no current studies examining the association between OSA and hypertension using new definitions,” Dr. Quan said.

He reported on results from an analysis of 6,307 participants in the Sleep Heart Health Study who underwent home polysomnography. Their AHI defined by a 3% oxygen desaturation or an arousal was classified into four categories of OSA severity: fewer than 5 events per hour (normal sleep), 5-14 events per hour (mild sleep apnea), 15-29 events per hour (moderate sleep apnea), and 30 or more events per hour (severe sleep apnea).

The researchers used three definitions of dichotomous BP elevation: elevated (greater than 120/80 mm Hg or use of hypertension medications [meds]), stage 1 (greater than 130/80 mm Hg or meds), or stage 2 (greater than 140/90 mm Hg or meds). They used logistic regression to assess the association between elevated BP and/or hypertension and OSA severity, controlling for demographics and body mass index. Additional analyses utilized multiple linear regression to determine the relationship between natural log AHI and systolic and diastolic BP, controlling for the same covariates.

For all definitions of elevated BP, increasing OSA severity was associated with greater likelihood of an elevated or hypertensive status in fully adjusted models. Specifically, the odds ratios among those with elevated BP was 1.30 (95% confidence interval, 1.10-1.54), 1.41 (95% CI, 1.15-1.72), and 1.69 (95% CI, 1.32-2.17) for mild, moderate, and severe sleep apnea, respectively. The ORs among those with stage 1 BP was 1.27 (95% CI, 1.09-1.49), 1.36 (95% CI, 1.13-1.63), 1.58 (95% CI, 1.27-1.97) for mild, moderate, and severe sleep apnea, while the OR among those with stage 2 BP was 1.07 (95% CI, 0.92-1.26), 1.22 (95% CI, 1.02-1.45), 1.38 (95% CI, 1.12-1.69) for mild, moderate, and severe sleep apnea. Linear regression found that AHI was associated with both systolic and diastolic BP in fully adjusted models.

“Using the AASM and CMS AHI definitions, increasing severity of AHI is associated with greater likelihood of having an elevated blood pressure or hypertension,” Dr. Quan concluded. “However, the prevalence of OSA was substantially lower using the CMS definition of OSA. In fact, 218 of these individuals had moderate to severe OSA when the AASM definition was applied.”

He characterized the study as “a practical analysis, a way to help identify patients who might benefit from treatment. This is not the issue of whether the science of 3% AHI is better than 4%.”

The Sleep Heart Health Study was supported by the National Heart, Lung, and Blood Institute. Dr. Quan reported that he helped draft the AASM AHI recommendations but had no other relevant disclosures.

[email protected]

SOURCE: Quan SF et al. SLEEP 2019, Abstract 0501.

SAN DIEGO – The prevalence of obstructive sleep apnea (OSA) is substantially lower using the Centers for Medicare & Medicaid Services apnea-hypopnea index definition of OSA than using the one recommended by the American Academy of Sleep Medicine.

Doug Brunk/MDedge News

In addition, among individuals who did not have OSA using the CMS definition but met criteria using the AASM definition of OSA, an apnea-hypopnea index (AHI) of five events or greater per hour was associated with a greater likelihood of having hypertension.

The findings come from an analysis which set out to assess the relationship between OSA and hypertension using the AASM-recommended definition and the 2018 American Heart Association/American College of Cardiology blood pressure guidelines, and to determine if there is an association between hypertension and OSA among individuals who did not meet the CMS definition of OSA.

“Given the substantial morbidity associated with hypertension, these results suggest that universal adoption of the AASM AHI definition would be a reasonable step in ensuring appropriate diagnosis and treatment of OSA,” lead study author Stuart F. Quan, MD, said at the annual meeting of the Associated Professional Sleep Societies.

Dr. Quan, of the division of sleep and circadian disorders at Brigham and Women’s Hospital in Boston, noted that a number of studies have demonstrated that OSA is a risk factor for hypertension and a variety of other medical conditions. “Rightly or wrongly, the most important metric for determining whether OSA is present and determining its severity, is the apnea-hypopnea index,” he said. “It’s the most common metric used for determining OSA severity, and mostly importantly, Medicare and some other insurers use this metric to determine whether a person is eligible for treatment. If a person falls above the line, they can get continuous positive airway pressure, for example. If they’re below the line, that’s too bad; they don’t have OSA insofar as the insurance company is concerned.”

There is no controversy as to what constitutes apnea, he continued, but some disagreement exists on the definition of hypopnea. The AASM recommends using a 3% oxygen desaturation or an arousal, while Medicare uses a definition of hypopnea requiring only a 4% oxygen desaturation. Hypertension definitions have changed recently as well. Before 2018, the definition of hypertension was greater than 140/90 mm Hg for people younger than age 65 years and 150/80 mm Hg for people age 65 years and older. In 2018, the AHA and ACC changed the hypertension guidelines, defining normal as less than 120/80 mm Hg.

“Previous studies linking OSA and hypertension used older definitions, but to my knowledge there are no current studies examining the association between OSA and hypertension using new definitions,” Dr. Quan said.

He reported on results from an analysis of 6,307 participants in the Sleep Heart Health Study who underwent home polysomnography. Their AHI defined by a 3% oxygen desaturation or an arousal was classified into four categories of OSA severity: fewer than 5 events per hour (normal sleep), 5-14 events per hour (mild sleep apnea), 15-29 events per hour (moderate sleep apnea), and 30 or more events per hour (severe sleep apnea).

The researchers used three definitions of dichotomous BP elevation: elevated (greater than 120/80 mm Hg or use of hypertension medications [meds]), stage 1 (greater than 130/80 mm Hg or meds), or stage 2 (greater than 140/90 mm Hg or meds). They used logistic regression to assess the association between elevated BP and/or hypertension and OSA severity, controlling for demographics and body mass index. Additional analyses utilized multiple linear regression to determine the relationship between natural log AHI and systolic and diastolic BP, controlling for the same covariates.

For all definitions of elevated BP, increasing OSA severity was associated with greater likelihood of an elevated or hypertensive status in fully adjusted models. Specifically, the odds ratios among those with elevated BP was 1.30 (95% confidence interval, 1.10-1.54), 1.41 (95% CI, 1.15-1.72), and 1.69 (95% CI, 1.32-2.17) for mild, moderate, and severe sleep apnea, respectively. The ORs among those with stage 1 BP was 1.27 (95% CI, 1.09-1.49), 1.36 (95% CI, 1.13-1.63), 1.58 (95% CI, 1.27-1.97) for mild, moderate, and severe sleep apnea, while the OR among those with stage 2 BP was 1.07 (95% CI, 0.92-1.26), 1.22 (95% CI, 1.02-1.45), 1.38 (95% CI, 1.12-1.69) for mild, moderate, and severe sleep apnea. Linear regression found that AHI was associated with both systolic and diastolic BP in fully adjusted models.

“Using the AASM and CMS AHI definitions, increasing severity of AHI is associated with greater likelihood of having an elevated blood pressure or hypertension,” Dr. Quan concluded. “However, the prevalence of OSA was substantially lower using the CMS definition of OSA. In fact, 218 of these individuals had moderate to severe OSA when the AASM definition was applied.”

He characterized the study as “a practical analysis, a way to help identify patients who might benefit from treatment. This is not the issue of whether the science of 3% AHI is better than 4%.”

The Sleep Heart Health Study was supported by the National Heart, Lung, and Blood Institute. Dr. Quan reported that he helped draft the AASM AHI recommendations but had no other relevant disclosures.

[email protected]

SOURCE: Quan SF et al. SLEEP 2019, Abstract 0501.

SAN DIEGO – The prevalence of obstructive sleep apnea (OSA) is substantially lower using the Centers for Medicare & Medicaid Services apnea-hypopnea index definition of OSA than using the one recommended by the American Academy of Sleep Medicine.

Doug Brunk/MDedge News

In addition, among individuals who did not have OSA using the CMS definition but met criteria using the AASM definition of OSA, an apnea-hypopnea index (AHI) of five events or greater per hour was associated with a greater likelihood of having hypertension.

The findings come from an analysis which set out to assess the relationship between OSA and hypertension using the AASM-recommended definition and the 2018 American Heart Association/American College of Cardiology blood pressure guidelines, and to determine if there is an association between hypertension and OSA among individuals who did not meet the CMS definition of OSA.

“Given the substantial morbidity associated with hypertension, these results suggest that universal adoption of the AASM AHI definition would be a reasonable step in ensuring appropriate diagnosis and treatment of OSA,” lead study author Stuart F. Quan, MD, said at the annual meeting of the Associated Professional Sleep Societies.

Dr. Quan, of the division of sleep and circadian disorders at Brigham and Women’s Hospital in Boston, noted that a number of studies have demonstrated that OSA is a risk factor for hypertension and a variety of other medical conditions. “Rightly or wrongly, the most important metric for determining whether OSA is present and determining its severity, is the apnea-hypopnea index,” he said. “It’s the most common metric used for determining OSA severity, and mostly importantly, Medicare and some other insurers use this metric to determine whether a person is eligible for treatment. If a person falls above the line, they can get continuous positive airway pressure, for example. If they’re below the line, that’s too bad; they don’t have OSA insofar as the insurance company is concerned.”

There is no controversy as to what constitutes apnea, he continued, but some disagreement exists on the definition of hypopnea. The AASM recommends using a 3% oxygen desaturation or an arousal, while Medicare uses a definition of hypopnea requiring only a 4% oxygen desaturation. Hypertension definitions have changed recently as well. Before 2018, the definition of hypertension was greater than 140/90 mm Hg for people younger than age 65 years and 150/80 mm Hg for people age 65 years and older. In 2018, the AHA and ACC changed the hypertension guidelines, defining normal as less than 120/80 mm Hg.

“Previous studies linking OSA and hypertension used older definitions, but to my knowledge there are no current studies examining the association between OSA and hypertension using new definitions,” Dr. Quan said.

He reported on results from an analysis of 6,307 participants in the Sleep Heart Health Study who underwent home polysomnography. Their AHI defined by a 3% oxygen desaturation or an arousal was classified into four categories of OSA severity: fewer than 5 events per hour (normal sleep), 5-14 events per hour (mild sleep apnea), 15-29 events per hour (moderate sleep apnea), and 30 or more events per hour (severe sleep apnea).

The researchers used three definitions of dichotomous BP elevation: elevated (greater than 120/80 mm Hg or use of hypertension medications [meds]), stage 1 (greater than 130/80 mm Hg or meds), or stage 2 (greater than 140/90 mm Hg or meds). They used logistic regression to assess the association between elevated BP and/or hypertension and OSA severity, controlling for demographics and body mass index. Additional analyses utilized multiple linear regression to determine the relationship between natural log AHI and systolic and diastolic BP, controlling for the same covariates.

For all definitions of elevated BP, increasing OSA severity was associated with greater likelihood of an elevated or hypertensive status in fully adjusted models. Specifically, the odds ratios among those with elevated BP was 1.30 (95% confidence interval, 1.10-1.54), 1.41 (95% CI, 1.15-1.72), and 1.69 (95% CI, 1.32-2.17) for mild, moderate, and severe sleep apnea, respectively. The ORs among those with stage 1 BP was 1.27 (95% CI, 1.09-1.49), 1.36 (95% CI, 1.13-1.63), 1.58 (95% CI, 1.27-1.97) for mild, moderate, and severe sleep apnea, while the OR among those with stage 2 BP was 1.07 (95% CI, 0.92-1.26), 1.22 (95% CI, 1.02-1.45), 1.38 (95% CI, 1.12-1.69) for mild, moderate, and severe sleep apnea. Linear regression found that AHI was associated with both systolic and diastolic BP in fully adjusted models.

“Using the AASM and CMS AHI definitions, increasing severity of AHI is associated with greater likelihood of having an elevated blood pressure or hypertension,” Dr. Quan concluded. “However, the prevalence of OSA was substantially lower using the CMS definition of OSA. In fact, 218 of these individuals had moderate to severe OSA when the AASM definition was applied.”

He characterized the study as “a practical analysis, a way to help identify patients who might benefit from treatment. This is not the issue of whether the science of 3% AHI is better than 4%.”

The Sleep Heart Health Study was supported by the National Heart, Lung, and Blood Institute. Dr. Quan reported that he helped draft the AASM AHI recommendations but had no other relevant disclosures.

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SOURCE: Quan SF et al. SLEEP 2019, Abstract 0501.