Cardiovascular medication use in patients with undiagnosed obstructive sleep apnoea.

BACKGROUND: A study was undertaken in patients with undiagnosed sleep apnoea/hypopnoea syndrome (OSAS) to document the use of prescribed medications, especially those used in cardiovascular diseases, in the year before the OSAS diagnosis was confirmed. METHODS: A total of 549 patients with OSAS (401 men of mean age 47.2 years, mean body mass index (BMI) 35.5 kg/m(2), mean apnoea/hypopnoea index (AHI) 47.2 and148 women of mean age 50.2 years, BMI 39.6 kg/m(2), AHI 32.6) were each matched to one general population control by age, sex, geographical location, and family physician. Medication use was evaluated for patients and controls using a database containing information about all prescriptions completed in the province of Manitoba, Canada. RESULTS: In the year before OSAS was diagnosed, prescribed medication costs were $155.91 (Canadian dollars) (95% CI $91.34 to $220.49) greater for cases than for controls. Cases were dispensed 3.3 (95% CI 1.5 to 5.2) more prescriptions, were on 1.2 (95% CI 0.8 to 1.6) more medications, and were supplied with 157.4 (95% CI 95.9 to 218.8) more daily doses of medication. The odds ratio of OSAS cases being on a prescribed medication was 1.88 relative to controls (95% CI 1.38 to 2.54, p<0.0001). In the same year 36.6% of cases and 19.7% of controls were using medications for cardiovascular disease (OR 2.82, 95% CI 2.05 to 3.89, p<0.0001), consuming 79.4 (95% CI 48.9 to 109.8) more daily doses of medication, having been dispensed 1.7 (95% CI 1.0 to 2.4) more prescriptions, and at a $75.26 (95% CI $44.03 to $106.50) greater cost. The odds ratio of patients with OSAS being on medications indicated for the treatment of systemic hypertension was 2.71 (95% CI 1.96 to 3.77) relative to controls; however, such medications might also be prescribed for other indications such as angina pectoris and congestive heart failure, and for the secondary prevention of myocardial infarction. The use of medications indicated for the treatment of systemic hypertension was predicted significantly by age (odds ratio (OR) 1.10 per year), BMI (OR 1.05 per unit), and AHI (OR 1.01 per unit). CONCLUSIONS: In the year before OSAS was diagnosed, patients with OSAS were heavy users of medications, particularly those used to treat cardiovascular diseases.

The use of health-care resources in obesity-hypoventilation syndrome.

OBJECTIVE: To document health-care utilization (ie, physician claims and hospitalizations) in patients with obesity-hypoventilation syndrome (OHS), for 5 years prior to the diagnosis and for 2 years after the diagnosis and initiation of treatment. DESIGN: Retrospective observational cohort study. SETTING: University-based sleep disorders center in Manitoba, Canada. PATIENTS AND CONTROL SUBJECTS: Twenty OHS patients (mean [+/- SD] age, 52.7 +/- 9.5 years; body mass index [BMI], 47.3 +/- 11.0 kg/m(2); PaCO(2), 59.7 +/- 13.8 mm Hg; PaO(2), 51.6 +/- 12.4 mm Hg) were matched to two sets of control subjects. First, each case was matched to 15 general population control subjects (GPCs) by age, gender, and geographic location, and, second, each case was matched to a single obese control subject (OBC) who was matched using the same criteria as for the GPCs, plus the measurement of BMI. MEASUREMENTS AND RESULTS: In the 5 years before diagnosis, the 20 OHS patients had (mean +/- SE) 11.2 +/- 1.8 physician visits per patient per year vs 5.7 +/- 0.8 (p < 0.01) visits for OBCs and 4.5 +/- 0.4 (p < 0.001) visits for GPCs. OHS patients generated higher fees, $623 +/- 96 per patient per year for the 5 years prior to diagnosis compared to $252 +/- 34 (p < 0.001) for OBCs and $236 +/- 25 (p < 0.001) for GPCs. OHS patients were much more likely to be hospitalized than were subjects in either control group in the 5 years prior to diagnosis (odds ratio [OR] vs GPCs, 8.6) (95% confidence interval [CI], 5.9 to 12.7); OR vs OBCs, 4.9 (95% CI, 2.3 to 10.1). In the 2 years after diagnosis and the initiation of treatment (usually continuous positive airway pressure or bilevel positive airway pressure), there was a significant linear reduction in physician fees. In the 2 years after the initiation of treatment, there was a 68.4% decrease in days hospitalized per year (5 years before treatment, 7.9 days per patient per year; after 2 years of treatment, 2.5 days per patient per year [p = 0.01]). CONCLUSIONS: OHS patients are heavy users of health care for several years prior to evaluation and treatment of their sleep breathing disorder; there is a substantial reduction in days hospitalized once the diagnosis is made and treatment is instituted.

Sleep complaints and restless legs syndrome in adult type 2 diabetics.

OBJECTIVE: To determine the prevalence and characteristics of sleep complaints and restless legs syndrome (RLS) in type 2 adult diabetics. To test the hypothesis that sleep complaints are more common among adult diabetics. BACKGROUND: Restless legs syndrome is a common disorder and is a cause of insomnia and daytime somnolence. An association between RLS and diabetes mellitus has been hypothesized but has not been established. METHODS: Consecutive type 2 diabetic patients and controls were subjected to sleep questionnaires, examinations for sensory neuropathy, and laboratory investigations. RESULTS: Diabetics had higher rates of insomnia (50 vs. 31%, P=0.04) and used more hypnotics (25.9 vs. 6.0%, P=0.02) than controls. The proportion of diabetics with elevated Epworth Sleepiness Scores (> or =12) was higher than controls (15.5 vs.2.1%, P=0.02). The prevalence of RLS among diabetics was not significantly different than in controls (24.1 vs. 12.5%, P=0.1). The prevalence of sensory polyneuropathy was similar in diabetics with and without RLS. Age, BMI, duration and level of diabetes control, hemoglobin, ferritin and creatinine levels did not predict the presence of RLS in diabetics. CONCLUSIONS: Adult type 2 diabetics have higher rates of insomnia, excessive somnolence and hypnotic use than controls. There is no evidence that RLS is significantly more common in adult diabetics.

Diagnosis and management of sleep apnea syndrome.

Sleep apnea is the cessation of breathing during sleep. These episodes result in hypoxemia and sleep disruption; thus the consequences are both cardiorespiratory and neural. Sleep apnea syndrome is defined by a constellation of signs and symptoms, with the main presenting symptom being excessive daytime sleepiness. A diagnosis requires documentation of episodes of abnormal breathing during sleep. This disorder, once thought to be very rare, is so common that it is unlikely that any busy clinician has not encountered a case. Facilities for the evaluation of sleep breathing disorders are now available in most communities. With the introduction of continuous positive airway pressure and other treatments, most patients have complete resolution of their disabling symptoms.

Health care utilization in males with obstructive sleep apnea syndrome two years after diagnosis and treatment.

OBJECTIVE: To document changes in health care utilization (physician claims and hospitalizations) two years after diagnosis and treatment of patients with OSAS. DESIGN: Prospective observational cohort study. SETTING: The study was done in the Canadian Province of Manitoba. OSAS patients were selected from a University-based sleep disorders center. Control subjects were selected from the general population. PATIENTS AND CONTROLS: There were 344 OSAS patients on whom there was utilization data for the period of the study. They were matched to controls from the general population by gender, age, and geographic location. MEASUREMENTS AND RESULTS: The difference in physician claims between the patients and their matched controls two years after diagnosis and treatment ($174+/-32.4 (SE) per year in Canadian dollars) was significantly less than the difference in the year before diagnosis ($260+/-35.7 (SE), p=0.038). Examining the subgroups of patients adhering (PAT) or not adhering (PNAT) to treatment revealed that the changes were only significant in the patients adhering to treatment. Hospital stays for the entire OSAS group decreased from 1.27 days+0.25(SE) per patient per year one year before diagnosis to 0.54+0.13 per patient per year (p=0.01). The changes in the PAT group (1.25+0.28 per patient per year one year before diagnosis to 0.53+0.14 per patient per year (p=0.034) were significant while in the PNAT group they were not. CONCLUSIONS: Adherence to treatment in patients with OSAS results in a significant reduction in physician claims and hospital stays.

Upper airway resistance syndrome: effect of nasal dilation, sleep stage, and sleep position.

BACKGROUND: The upper airway resistance syndrome (UARS) is one of the mild variants of obstructive sleep disordered breathing. Nasal obstruction is proposed as one of the mechanisms that lowers intrapharyngeal pressure and hence increases airway collapsibility. OBJECTIVE: We evaluated the effect of external nasal dilation and sleep position on sleep in UARS. METHOD: A double blind, randomized, controlled study with a crossover design (using therapeutic and placebo dilators) was conducted in 18 consecutive patients with UARS. Each patient had two overnight sleep studies one to two weeks apart. Cardiorespiratory parameters (AHI, percentage of time that SaO2 was more than 2% below awake [desaturation time] and mean overnight heart rate), sleep architecture (sleep stages, sleep efficiency, and arousal index), and body position were determined. RESULTS: Application of the external nasal dilator resulted in a significant increase in the nasal cross-sectional area (p < 0.001). Treatment reduced stage 1 sleep (as a percent of total sleep time) from 8.6 +/- 0.8% to 7.1 +/- 0.7 (SEM), p = 0.034). Desaturation time was significantly lower with treatment (12.2 +/- 2.2% on placebo versus 9.1 +/- 1.3 on treatment, p = 0.04). There were no additional significant effects on the cardiorespiratory parameters, sleep architecture, or MSLT when the entire night was examined. Controlling for interactions of sleep stage and position and treatment we found that treatment reduced desaturation time (p = 0.03) but not AHI or arousal index. AHI was significantly lower in the lateral position compared to the supine (p = 0.0001) and in NREM sleep compared to REM (p = 0.001). Desaturation time was significantly lower on the lateral compared to the supine position (p = 0.002) and in NREM sleep compared to REM (p = 0.006). Arousal index was highly dependent on sleep stage (p = 0.0001): the index was higher in stage 2 compared to slow wave sleep and REM. Sleep position and treatment had no significant effect on arousals. CONCLUSIONS: External nasal dilation reduced stage 1 sleep, an indirect marker of disrupted sleep, and desaturation time. There were no additional effects on sleep architecture or sleep disordered breathing. Both sleep position and sleep stage had a significant effect on sleep disordered breathing in UARS.

Clinical presentations of obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common but still underrecognized disorder. It affects 2% to 4% of middle-aged adults, a significant proportion of whom are female. The spectrum of clinical presentations of OSAS and their severity is variable, ranging from neurocognitive complaints to cardiorespiratory failure. OSAS has a significant impact on quality of life, cardiovascular morbidity, and mortality. Its major sequelae include daytime somnolence and its consequences (motor vehicle accidents, poor work performance, disrupted social interactions), systemic and pulmonary hypertension, and ischemic heart disease. Treatment of OSAS results in improvement in symptoms, quality of life, and blood pressure control, and may improve mortality. An expansion of our understanding of this condition has resulted in increased awareness of its consequences, but the recognition of OSAS in clinical practice is still delayed. Identification of these patients in clinical practice requires attention to risk factors (history of snoring and witnessed apneas, obesity, increased neck circumference, hypertension, family history) and careful examination of the upper airway. Clinical impression alone, however, has poor (50% to 60%) sensitivity and specificity (63% to 70%) and the diagnosis is usually obtained on polysomnography. Physicians and other health care professionals need to be aware of the progress made in this area and recognize the necessity for prompt evaluation and treatment of these patients.

Health care utilization in the 10 years prior to diagnosis in obstructive sleep apnea syndrome patients.

Obstructive sleep apnea syndrome (OSAS) patients may have symptoms for years prior to recognition of their disorder, or they may be treated for the associated comorbidities. We hypothesized that such patients would be heavy consumers of health care resources for several years prior to diagnosis. We therefore compared health service utilization for a 10-year interval prior to diagnosis of 181 OSA patients to those of randomly selected age-, gender-, and geographically matched controls from the general population. OSAS patients used approximately twice as many health care services (as defined by physician claims and overnight stays in hospital) in the 10 years prior to their initial diagnostic evaluation for apnea. Physician claims for the OSA patients totaled $686,365 ($3972 per patient), compared to $356,376 ($1969 per patient) for the controls for the 10-year period examined in this study. Use of health services was significantly higher in 7 of 10 years prior to diagnosis. The OSAS patients also had more overnight hospitalizations: they spent 1118 nights (6.2 per patient) in hospital vs 676 nights (3.7 per patient) for controls in the decade prior to diagnosis. We conclude that by the time patients are finally diagnosed for sleep apnea, they have already been heavy users of health services for several years. It is possible that our findings reflect not OSAS per se, but the presence of some of the risk factors that predispose to OSAS, such as obesity, alcohol usage and perhaps tobacco consumption.

Susceptibility of LDL to oxidative stress in obstructive sleep apnea.

Cardiovascular diseases are more common in patients with obstructive sleep apnea (OSA) than in the general population. We hypothesized that severe hypoxemia during sleep in these patients may cause an imbalance between reactive oxygen species and the antioxidant reserve that is important for the detoxification of these molecules. We tested the hypothesis that low-density lipoproteins (LDL) in hypoxic OSA patients may be more susceptible to oxidative stress than LDL of nonhypoxic OSA patients and normal controls. Fifteen OSA patients were included in this study, six with severe hypoxia (hypoxic group) who spent more than 10 minutes during sleep with SaO2 < 85% (mean 96 minutes), and nine OSA patients (nonhypoxic group) who spent less than 10 minutes during sleep with SaO2 < 85% (mean 1.1 minutes). Six healthy nonsmoking males of the same age group were included as a control group. The susceptibility of each individual's LDL to oxidative stress was examined after free-radical challenge in vitro by assessing changes in levels of conjugated dienes. The LDL in OSA patients with severe hypoxia was not more susceptible to oxidative stress compared to the LDL of nonhypoxic OSA patients and normal controls. After 6 hours of exposure to an oxidative agent, the changes in the mean conjugated diene were not different among the three groups (p = 0.75). The time required to reach 50% of maximal absorbance was also not different, p = 0.199. Glutathione peroxidase and catalase activities in red blood cells in the hypoxic and nonhypoxic patient groups were not significantly different. One night of CPAP therapy in each patient group did not significantly change the level of the antioxidant enzymes. Our results did not show any difference in the susceptibility to oxidative stress between hypoxic and nonhypoxic OSA patients and normal controls.

Obstructive sleep apnea patients use more health care resources ten years prior to diagnosis.

Because Obstructive Sleep Apnea Syndrome (OSAS) patients may be treated for comorbidities prior to OSAS diagnosis, we examined the health care utilization records of 181 OSAS patients and those of matched controls. We compared OSA patient health care utilization for a ten-year interval prior to diagnosis to those of randomized age-, gender-, and geographically-matched controls from the general population. We found that OSAS patients used approximately twice the resources (as defined by physician claims and stays in hospital) in the ten years prior to their diagnosis. Physician claims for cases totaled $686,365 ($3,972 per patient) compared to $356,376 ($1,969 per patient) for the controls for the length of the study. Utilization was significantly higher in 7 of 10 years prior to diagnosis. OSAS patients also had more hospitalizations: they had 1,118 nights (6.2 per patient) in hospital versus 676 nights (3.7 per patient) for controls over the ten-year period. Thus OSA patients are heavy users of health care resources ten years prior to diagnosis.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.

Using self-reported questionnaire data to prioritize OSA patients for polysomnography.

Many laboratories have large numbers of patients with suspected obstructive sleep apnea (OSA) waiting to be tested. We assessed the use of simple clinical data to detect those patients with an apnea index <20 (low AI) who could be studied less emergently. Using questionnaires completed by patients prior to evaluation, we collected data on 354 consecutive patients (281 males, 73 females; mean age 48.6 years) referred for OSA and assessed with polysomnography (PSG). The questionnaires included the Epworth sleepiness scale (ESS), height, weight, age, and a history of observed apnea. Analysis of receiver operating characteristics curves revealed that both body mass index (BMI) [area under curve = 0.7258, standard error (SE) = 0.03, p < 0.01] and ESS (area under curve = 0.5581, SE = 0.03, p = 0.03) were significantly better than chance alone in detecting people with AI < 20. ESS < or =12 was found in 37.9% of the subjects but 39.6% of those expected to have a low AI using ESS had an AI > or =20. A BMI < or =28 was found in 24.9% of the subjects; 14.8% of those expected to have a low AI using BMI had an AI > or =20. Combining these variables improved accuracy but resulted in smaller groups; a cut-off of ESS < or =12 and BMI < or =28 resulted in a group of 33 (9.3% of subjects), only two (6%) of whom were falsely called low AI. Adding to this the fact that apnea had not been observed resulted in a group of nine patients (2.5% of subjects), none of whom had an AI > or =20. Thus there is a tradeoff; the more variables used, the greater the accuracy but the smaller the percent of cases selected to have low AI. However, in laboratories with hundreds of patients waiting to be tested, any procedure better than chance to help prioritize patients seems worthwhile.

Utilization of health care services in patients with severe obstructive sleep apnea.

We compared the health care utilization of 97 obese patients diagnosed with obstructive sleep apnea (OSA) and 97 matched control subjects. Over a 2-year period that ended 2 years prior to initial diagnosis, the OSA group had 251 nights in hospital, compared to 90 nights for the control group. During the same 2-year period, total expenditures from physician claims were $82,238 (Canadian dollars) in the OSA patients versus $41,018 in the control group (p < 0.01). Depending upon which assumptions one uses for the calculation of hospital costs, during the same 2-year period, the 97 OSA patients utilized between $100,000 and $200,000 more in services than their control counterparts. We conclude that sleep apnea patients are already heavy consumers of health care services prior to any specific evaluation and treatment for apnea.

L-DOPA/carbidopa for nocturnal movement disorders in uremia.

Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) are sleep disorders that are common and distressing to uremic patients. There are few data regarding effective treatment in this population. Five chronic hemodialysis patients completed a double-blind, placebo-controlled, crossover study using a single bedtime dose of controlled release L-DOPA/carbidopa (100/25 mg) for treatment of RLS and sleep disruption. Leg movements per hour of sleep and percentage of sleep time accompanied by leg movements were decreased with treatment (101.0 +/- 29.1 events/hour on placebo vs. 61.0 +/- 28.3 events per hour on drug, p = 0.006; and 15.1 +/- 4.9% of sleep time with leg movements on placebo vs. 8.6 +/- 4.0% on drug, p = 0.014). In addition, arousals associated with leg movements (mean 209 +/- 49 events on placebo, mean 108 +/- 46 events on drug) and the leg movement arousal index (mean 59 +/- 23 events/hour on placebo, mean 23 +/- 9 events/hour on drug) were decreased by active medication (p = 0.03 and 0.04, respectively). Patients, however, continued to have very disrupted sleep and we could not document consistent subjective or objective improvement in overall sleep except for an increase in slow-wave sleep (SWS) from 9.0% to 22.8% (p = 0.01). The patterns of movements during sleep were not uniform in different patients, and the movements, although often periodic, were much longer than defined for PLMS. Because of this, finding suitable objective parameters to analyze was problematic. Measuring the percentage of sleep time during which there were leg movements was probably the most efficient and reproducible means of quantitating this disorder. Thus, although controlled-release L-DOPA/carbidopa at a dose of 100/25 mg given once nightly reduced leg movements and increased SWS, sleep continued to be disrupted. Whether higher doses or more frequent dosing is effective requires further investigation.

Effect of severe gastroesophageal reflux on sleep stage in patients with aperistaltic esophagus.

Polysomnography and esophageal pH studies were conducted in 13 patients with an aperistaltic esophagus; seven of these had scleroderma and six were patients treated for achalasia. The percentage total time of pH<4.0 when recumbent exceeded 30% for both groups. There was a total of 51 reflux events for both groups. There were 22 reflux events recorded for both groups that were less than 5 min in length and 29 events greater than 5 min. In 26 of 32 (81%) instances, patients either began awake and went to sleep during a reflux event or did not awake during a reflux event. Only six of 32 (19%) reflux events caused sleep disruption. We conclude that even the severe reflux demonstrated in this subset of patients does not always disrupt sleep. Patients may have severe prolonged reflux and not arouse.

Sleep complaints are common in a dialysis unit.

Sleep disturbance among uremic patients is reported to be high, but data on the actual prevalence, clinical significance, and causative factors is limited. A sleep questionnaire was distributed to an entire hemodialysis unit of 64 patients. Of the 54 patients who completed the survey, 83.3% had sleep-wake complaints. Disturbed sleep was reported by 28 patients (51.8%), and causes were secondary to delayed sleep onset in 25 patients (46.3%), frequent awakening in 19 patients (35.2%), restless legs syndrome (RLS) in 18 patients (33.3%), and generalized restlessness in six patients (11.1%). Daytime sleepiness was the most frequent complaint, reported by 36 patients (66.7%), and RLS was the second most frequent specific complaint, reported by 31 patients (57.4%). Symptoms of sleep apnea were described by seven patients (13.0%). Male gender, age more than 60 years, RLS, and caffeine intake were associated with more sleep-wake complaints (P = 0.009, P = 0.002, P = 0.028, and P = 0.008, respectively). Urea and creatinine levels were higher in patients with RLS (P = 0.04 and P = 0.08, respectively); otherwise, no other metabolic or demographic variable was associated with specific sleep disorders or disturbance. Sleep problems are very common in dialysis patients and likely contribute to the impaired quality of life experienced by many of these patients.

Medical treatment of sleep apnea.

Obstructive sleep apnea is a common disorder. Since 1981 the treatment of choice has shifted from tracheostomy or weight loss to uvulopalatopharyngoplasty and then to continuous positive airway pressure. This review encompasses the most recent literature, focusing mainly on current treatment options and other potential and experimental modes of therapy. We review in detail continuous positive airway pressure therapy, including unwanted effects; compliance and possible ways to improve it; and ways to deal with the difficult patient. We also review dental appliances, electrical stimulation, and potential hormonal and nicotine treatment.

A familial awake movement disorder mimicking restless legs in a sleep apnea patient.

We report on a patient with sleep apnea and an unusual familial movement disorder. The movements were present only during wakefulness and nocturnal arousals caused by disordered breathing. A 27-year-old obese man was referred with sleep onset insomnia, symptoms suggesting restless legs syndrome, daytime sleepiness, loud snoring and awakening with choking sensations. He was proven to have obstructive sleep apnea (apnea hypopnea index = 60.6). He also had a daytime movement disorder that was characterized by almost continuous stereotypic tapping of one or both legs. The movements were suppressible and not associated with any unpleasant or abnormal leg sensation. Virtually identical movements were present in three generations of his family. The severity of the movements did not worsen late in the day or with supine posturing. The nocturnal movements, consisting of a visible shaking of one or both legs, occurred only during arousals secondary to the apnea, had a mean duration of 5.7 +/- 3.0 (standard deviation) seconds and could not be defined as periodic limb movements in sleep (PLMS). Successful treatment of apnea by nasal continuous positive airway pressure dramatically reduced the movements during sleep (from 88.2 to 1.9 per hour). The clinical significance and the mechanism of this movement disorder is unknown. We discuss the features inconsistent with restless legs syndrome and consider other possible phenomenology, including akathisia. We conclude that this patient may have a previously unreported familial movement disorder and in addition developed the sleep apnea syndrome related to obesity.