Treatment of central sleep apnea in heart failure

Recent studies show that central sleep apnea occur in about 40% of patients with heart failure and systolic dysfunction. The pathophysiological consequences of central sleep apnea may contribute to morbidity and mortality of heart failure. Three treatment modalities, oxygen, continuous positive airway pressure and theophylline have been shown to decrease periodic breathing modestly with considerable improvement in arterial oxyhemoglobin desaturation, and variable effects on sleep characteristics. However, long-term effects of central sleep apnea and its treatment on the natural history of heart failure remain to be determined.     

Severity of sleep-disordered breathing improves following parturition

STUDY OBJECTIVE: Changes in sleep-disordered breathing associated with late pregnancy have not previously been systematically investigated; however, a number of case reports indicate exacerbation of obstructive sleep apnea in late pregnancy, often in association with maternal hypertension. We aimed to compare the severity of sleep-disordered breathing and associated maternal blood-pressure responses in late pregnancy with the nonpregnant state. DESIGN: Case-controlled, longitudinal study of sleep-disordered breathing during late pregnancy and postpartum. Study Patients: Ten women referred for suspected sleep-disordered breathing during the third trimester of pregnancy. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Full overnight polysomnography and continuous systemic blood pressure were measured during the third trimester of pregnancy and 3 months following delivery. Parameters of sleep-disordered breathing, including apnea hypopnea index and minimum overnight arterial oxyhemoglobin saturation, were compared between antenatal and postnatal studies. An improvement in both apnea-hypopnea index and minimum arterial oxyhemoglobin saturation occurred consistently in all subjects postnatally. In non-rapid eye movement sleep, mean apnea-hypopnea index was reduced from 63 +/- 15 per hour antenatally to 18 +/- 4 per hour postnatally (P = .03), and in rapid eye movement sleep, from 64 +/- 11 per hour to 22 +/- 4 per hour (P = .002). Minimum arterial oxyhemoglobin saturation was increased from 86% +/- 2% antenatally to 91% +/- 1% postnatally (P = .01). Arterial blood-pressure responses to apnea peaked at 170 to 180 mm Hg antenatally, while they only peaked at 130 to 140 mm Hg postnatally. CONCLUSION: This study indicates that late pregnancy may be associated with increased severity of sleep-disordered breathing and associated blood-pressure responses.     

A mechanism of central sleep apnea in patients with heart failure.

BACKGROUND: Breathing is controlled by a negative-feedback system in which an increase in the partial pressure of arterial carbon dioxide stimulates breathing and a decrease inhibits it. Although enhanced sensitivity to carbon dioxide helps maintain the partial pressure of arterial carbon dioxide within a narrow range during waking hours, in some persons a large hyperventilatory response during sleep may lower the value below the apneic threshold, thereby resulting in central apnea. I tested the hypothesis that enhanced sensitivity to carbon dioxide contributes to the development of central sleep apnea in some patients with heart failure. METHODS: This prospective study included 20 men who had treated, stable heart failure with left ventricular systolic dysfunction. Ten had central sleep apnea, and 10 did not. The patients underwent polysomnography and studies of their ventilatory response to carbon dioxide. RESULTS: Patients who met the criteria for central sleep apnea had significantly more episodes of central apnea per hour than those without central sleep apnea (mean [+/-SD], 35+/-24 vs. 0.5+/-1.0 episodes per hour). Those with sleep apnea also had a significantly larger ventilatory response to carbon dioxide than those without central sleep apnea (5.1+/-3.1 vs. 2.1+/-1.0 liters per minute per millimeter of mercury, P=0.007), and there was a significant positive correlation between ventilatory response and the number of episodes of apnea and hypopnea per hour during sleep (r=0.6, P=0.01). CONCLUSIONS: Enhanced sensitivity to carbon dioxide may predispose some patients with heart failure to the development of central sleep apnea.     

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.     

Effect of expiratory positive airway pressure on sleep disordered breathing

STUDY OBJECTIVES: We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN: Observational physiology study PARTICIPANTS: We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS: The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION: In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.     

Lateral sleeping position reduces severity of central sleep apnea / Cheyne-Stokes respiration

INTRODUCTION: The influence of sleeping position on obstructive sleep apnea severity is well established. However, in central sleep apnea with Cheyne Stokes respiration (CSA-CSR) in which respiratory-control instability plays a major pathophysiologic role, the effect of position is less clear. STUDY OBJECTIVES: To examine the influence of position on CSA-CSR severity as well as central and mixed apnea frequency. METHODS: Polysomnograms with digitized video surveillance of 20 consecutive patients with heart failure and CSA-CSR were analyzed for total apnea-hypopnea index, mean event duration, and mean oxygen desaturation according to sleep stage and position. Position effects on mixed and central apnea index, mean apnea duration, and mean desaturation were also examined in non-rapid eye movement sleep. RESULTS: Data are presented as mean +/- SEM unless otherwise indicated. Group age was 59.9 +/- 2.3 years, and total apnea-hypopnea index was 26.4 +/- 3.0 events per hour. Compared with supine position, lateral position reduced the apnea-hypopnea index in all sleep stages (Stage 1, 54.7 +/- 4.2 events per hour vs 27.2 +/- 4.1 events per hour [p < .001]; Stage 2, 43.3 +/- 6.1 events per hour vs 14.4 +/- 3.6 events per hour [p < .001]; slow-wave sleep, 15.9 +/- 6.4 events per hour vs 5.4 +/- 2.9 events per hour [p < .01]; rapid eye movement sleep, 38.0 +/- 7.3 events per hour vs 11.0 +/- 3.0 events per hour [p < .001]). Lateral position attenuated apnea and hypopnea associated desaturation (supine 4.7% +/- 0.3%, lateral 3.0% +/- 0.4%; p < .001) with no difference in event duration (supine 25.7 +/- 2.8 seconds, lateral 26.9 +/- 3.4 seconds; p = .921). Mixed apneas were longer than central (29.1 +/- 2.1 seconds and 19.3 +/- 1.1 seconds; p < .001) and produced greater desaturation (6.1% +/- 0.5% and 4.5% +/- 0.5%, p = .003). Lateral position decreased desaturation independent of apnea type (supine 5.4% +/- 0.5%, lateral 3.9% < or = 0.4%; p = .003). CONCLUSIONS: Lateral position attenuates severity of CSA-CSR. This effect is independent of postural effects on the upper airway and is likely to be due to changes in pulmonary oxygen stores. Further studies are required to investigate mechanisms involved.     

Sleep apnea in heart failure increases heart rate variability and sympathetic dominance

AIMS: Sleep disordered breathing (SDB) is common in heart failure and ventilation is known to influence heart rate. Our aims were to assess the influence of SDB on heart rate variability (HRV) and to determine whether central sleep apnea (CSA) and obstructive sleep apnea (OSA) produced different patterns of HRV. METHODS AND RESULTS: Overnight polysomnography was performed in 21 patients with heart failure and SDB. Two 10-minute segments each of SDB and stable breathing from each patient were visually identified and ECG signal exported for HRV analysis. SDB increased total power (TP) with very low frequency (VLF) power accounting for the greatest increase (1.89+/-0.54 vs 2.96+/-0.46 ms2, P <0.001); LF/HF ratio increased during SDB (1.2+/-1.0 vs 2.7+/-2.1, P <0.001). Compared to OSA, CSA was associated with lower absolute LF (2.10+/-0.47 vs 2.52+/-0.55 ms2, P = 0.049) and HF power (1.69+/-0.41 vs 2.34+/-0.58 ms2, P = 0.004), increased VLF% (78.9%+/-13.4% vs 60.9%+/-19.2%, P = 0.008), decreased HF% (6.9%+/-7.8% vs 16.0%+/-11.7%, P = 0.046) with a trend to higher LF/HF ratio. CONCLUSIONS: SDB increases HRV in the setting of increased sympathetic dominance. HRV in CSA and OSA have unique HRV patterns which are likely to reflect the different pathophysiological mechanisms involved.     

Night-to-night alterations in sleep apnea type in patients with heart failure

In patients with heart failure, apnea type can shift overnight from mainly obstructive to mainly central in association with reductions in PCO(2) and increases in periodic breathing cycle length, indicative of a fall in cardiac output. We hypothesized that the predominant apnea type could also vary from one night to another in association with alterations in PCO(2) and cycle length. We studied 12 men with heart failure in whom the predominant apnea type changed from one night to the next over periods of at least 1 month, and two groups with either predominantly obstructive or central sleep apnea (OSA or CSA) in whom apnea type remained stable over time. In patients with unstable apnea type (n = 12, duration between sleep studies 9.0 +/- 4.4 months), PCO(2) was significantly lower (37.6 +/- 1.6 mmHg versus 41.7 +/- 1.9 mmHg, P < 0.01), and cycle length significantly longer (61.9 +/- 3.4 s versus 51.0 +/- 1.9 s, P < 0.001) during nights with predominantly central than nights with predominantly obstructive apnea. In contrast, in both the stable central (n = 8, duration between sleep studies 11.9 +/- 5.3 months) and the stable obstructive (n = 8, duration between studies 6.9 +/- 5.2 months) sleep apnea groups, neither PCO(2) nor cycle length changed significantly between the baseline and follow-up sleep studies. We conclude that in some patients with heart failure, OSA and CSA are part of a spectrum of periodic breathing that can shift over time in association with alterations in PCO(2), cycle length and probably cardiac function.     

Sleep apnea syndrome: a possible contributing factor to resistant

STUDY OBJECTIVES: There is evidence supporting an association between sleep apnea and hypertension. However, it is not clear if sleep apnea interteres with the pharmacotherapy of hypertension. To investigate this question, we studied the relationship between the effectiveness of anti-hypertensive treatment in reducing blood pressure, and severity of sleep apnea in a large group of apneic patients referred to a sleep disorders centre at St. Michael's Hospital at the University of Toronto. DESIGN: N/A SETTING: N/A PARTICIPANTS: 1,485 adult patients with sleep apnea, as defined by the apnea/hypopnea index (AHI) >10 events/hr, were analyzed. There were 393 who reported using anti-hypertensive medications on a regular basis for more than 6 months. One hundred and eighty-three patients were treated "effectively" (i.e. blood pressure lower than 140/90 mm Hg in the morning and in the evening). Seventy-four patients were treated "ineffectively," defined as blood pressure >140/90 mm Hg in the morning or in the evening. Both groups were compared with respect to clinical and demographic data using analysis of covariance with gender, age, body mass index (BMI), and neck circumference (NC) as covariates. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Ineffectively and effectively treated patients were similar in age (57 +/- 9) vs. 57 +/- 10 years, respectively), and had similar body mass index (33.8 +/- 7.4 vs. 33.4 +/- 7.3 kg/m2, respectively). However, ineffectively treated patients had significantly higher apnea/hypopnea index (44 +/- 29 vs. 33 +/- 25 events/hr, p<.0005), despite having similar nocturnal oxygenation (percent of total sleep time spent with oxygen desaturation lower than 90% was 36 +/- 34 vs. 29 +/- 30% in the ineffective and effective groups, respectively). The difference in AHI persisted even after adjusting for age, gender, and body mass index. CONCLUSIONS: Our results demonstrate that hypertensive patients with sleep apnea whose blood pressure responds beneficially to treatment have less severe sleep apnea than those patients whose blood pressure remains elevated despite anti-hypertensive therapy. Since neither obesity nor nocturnal hypoxemia appear to be important determinants of ineffective treatment, we suggest that resistant hypertension may be caused by frequent intermittent sympathetic stimulation.     

Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and complex sleep apnea syndromes

RATIONALE: Although continuous positive airway pressure (CPAP) is most often effective in patients with obstructive sleep apnea, optimal treatment of patients with predominantly mixed apneas, central sleep apnea syndrome/Cheyne-Stokes respiration (CSA/CSR), or complex sleep apnea (CompSAS) is less straightforward, and may require alternative ventilatory assist modalities. OBJECTIVES: To compare the efficacy of noninvasive positive pressure ventilation (NPPV) with adaptive servoventilation (ASV) in treating patients with centrally mediated breathing abnormalities. We hypothesized that NPPV and ASV would be equivalently efficacious in improving the apnea/hypopnea index (AHI) and respiratory arousal index (RAI). METHODS: Prospective randomized crossover clinical trial comparing NPPV with ASV in patients with CSA/CSR, predominantly mixed apneas, and CompSAS in an acute setting. MEASUREMENTS AND MAIN RESULTS: 21 patients (6 with CSA/CSR, 6 with predominantly mixed apneas, and 9 with CompSAS) with initial diagnostic AHI +/- standard deviation 51.9 +/- 22.8/hr and RAI 45.5 < or = 26.5/hr completed the study. Following optimal titration with CPAP (N = 15), disturbed breathing and disturbed sleep remained high with mean AHI = 34.3 +/- 25.7 and RAI = 32.1 +/- 29.7. AHI and RAI were markedly reduced with both NPPV (6.2 +/- 7.6 and 6.4 +/- 8.2) and ASV (0.8 +/- 2.4 and 2.4 +/- 4.5). Treatment AHI and RAI were both significantly lower using ASV (P < 0.01). CONCLUSION: These data confirm that in patients with CSA/CSR, mixed apneas, and CompSAS, both NPPV and ASV are effective in normalizing breathing and sleep parameters, and that ASV does so more effectively than NPPV in these types of patients.     

Effect of zolpidem on the efficacy of continuous positive airway pressure as treatment for obstructive sleep apnea

STUDY OBJECTIVE: Assess the effect of the hypnotic zolpidem on the efficacy of nasal continuous positive airway pressure for treatment of Obstructive Sleep Apnea. DESIGN: Randomized double blind placebo controlled, cross-over study. SETTING: Veterans Administration Medical Center. PATIENTS: 16 patients with severe obstructive sleep apnea (apnea+ hypopnea index > 30/hr), on CPAP therapy for at least 6 months. INTERVENTION: Three sleep studies were performed over three consecutive weeks. On night one the pressure level required to prevent apnea, hypopnea, and snoring was determined. On the second and third study nights, either placebo (P) or 10 mg of zolpidem (Z) was given (random order) and subjects slept on the CPAP level determined on the first night. MEASUREMENTS: Sleep architecture, apnea + hypopnea index, arterial oxygen saturation. RESULTS: The sleep architecture was similar on the placebo and zolpidem nights except for a decrease in the sleep latency ( P: 23.5 +/- 4.7; Z: 13.1 +/- 3.3 minutes, P < 0.02) and a small decrease in the arousal index (P < 0.03) on zolpidem nights. The was no significant difference between placebo and zolpidem nights in the apnea + hypopnea index (P: 4.8 +/- 1.4 versus Z : 2.7 +/- 0.47 events/hour), oxygen desaturation index (1.46 +/- 0.53 versus 0.81 +/- 0.29 desaturations/hour), or the lowest SaO2 (91.4 +/- 0.6 versus 91.0 +/- 0.7%). CONCLUSIONS: Acute administration of zolpidem 10 mg does not impair the efficacy of an effective level of CPAP in patients with severe obstructive sleep apnea.     

Effect of doxapram on obstructive sleep apnea

To determine whether treatment with a respiratory stimulant, doxapram hydrochloride, would improve obstructive sleep apnea, we administered the drug to four patients with this disease. Subjects were given a bolus of doxapram, 0.5 mg X kg-1 lean body mass, followed by a 1 mg X min-1 infusion throughout the night on one night and placebo another night. Doxapram produced improvement in the average oxyhemoglobin desaturation during apneic and hypopneic episodes and decreased average apnea length, but did not change the average number of oxyhemoglobin desaturations per hour of sleep or sleep efficiency. We conclude that doxapram, when administered at levels known to increase ventilatory drive, does not decrease the number of disordered breathing events during sleep but does cause termination of these events at higher levels of oxyhemoglobin saturation.     

Fasting glycemia in sleep disordered breathing: lowering the threshold on oxyhemoglobin desaturation

STUDY OBJECTIVES: Commonly used definitions of sleep-disordered breathing (SDB) are based on identifying discrete events of breathing abnormalities during sleep that are accompanied by an oxyhemoglobin desaturation (delta SaO2) of at least 4%. However, it is not known whether disordered breathing events with oxyhemoglobin desaturation less than 4% are associated with clinical sequelae such as abnormalities in fasting glycemia. DESIGN: Cross-sectional study. SUBJECTS AND SETTING: Participants from the Sleep Heart Health Study (SHHS) with a fasting glucose measurement made within a year of the baseline polysomnogram. MEASUREMENTS AND RESULTS: SDB severity was defined using the apnea-hypopnea index (AHI) and the hypopnea index (HI) by counting events with different levels of oxyhemoglobin desaturation (0.0%-1.9%, 2.0%-2.9%, 3.0%-3.9%, > or = 4.0%). Fasting glucose levels were used to classify individuals into normal (<100 mg/dL), impaired (100-125 mg/dL), and diabetic (> or = 126 mg/dL) groups. Ordinal logistic regression was used to determine the adjusted relative odds of an abnormal glucose value across quartiles of the hypopnea index, independent of factors such as age, body mass index, waist circumference, and usual sleep duration. The prevalence of impaired and diabetic fasting glucose in the analytical sample was 32.9% and 5.8%, respectively. The covariate-adjusted relative odds of impaired or diabetic fasting glucose in the highest versus the lowest AHI quartile was 1.35 (95% CI: 1.04-1.76) for events with a delta SaO2 > or = 4.0%, 1.72 (95% CI: 1.20-2.48) for events with a delta SaO2 between 3.0%-3.9%, 1.41 (95% CI: 1.07-1.86) for events with a delta SaO2 between 2.0%-2.9%, and 1.07 (95% CI: 0.84-1.37) for events with a delta SaO2 between 0.0%-1.9%. The corresponding odds ratios for the HI were 1.47 (95% CI: 1.13-1.92), 2.25 (95% CI: 1.59-3.19), 1.44 (95% CI: 1.09-1.90), and 1.15 (95% CI: 0.90-1.47), respectively. CONCLUSIONS: The results of this study indicate that SDB events accompanied by oxyhemoglobin desaturation of between 2% to 4% are associated with fasting hyperglycemia. These findings suggest that milder degrees of SDB may predispose to adverse metabolic outcomes.     

Validation a portable monitoring device for sleep apnea diagnosis in a population based cohort using synchronized home polysomnography

SUBJECT OBJECTIVE: To assess the accuracy of a portable monitoring device based on peripheral arterial tonometry to diagnose obstructive sleep apnea (OSA). To propose a new standard for limited-channel device validation using synchronized polysomnography (PSG) home recordings and a population-based cohort. DESIGN: Single-night, unattended PSG and Watch_PAT 100 (WP_100). SETTING: Home environment. PARTICIPANTS: Ninety-eight subjects (55 men; age, 60 +/- 7 year; body mass index, 28 +/- 4 kg/m2) consecutively recruited from the Skaraborg Hypertension and Diabetes Project. MEASUREMENTS AND RESULTS: The WP_100 records peripheral arterial tone, heart rate, oxygen saturation and actigraphy for automatic analysis of respiratory disturbance index (RDI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and sleep-wake state. The accuracy of WP_100 in RDI, AHI, ODI, and sleep-wake detection was assessed by comparison with data from simultaneous PSG recordings. The mean PSG-AHI in this population was 25.5 +/- 22.9 events per hour. The WP_100 RDI, AHI, and ODI correlated closely (0.88, 0.90, and 0.92; p < .0001, respectively) with the corresponding indexes obtained by PSG. The areas under the curve for the receiver-operator characteristic curves for WP_100 AHI and RDI were 0.93 and 0.90 for the PSG-AHI and RDI thresholds 10 and 20 (p < .0001, respectively). The agreement of the sleep-wake assessment based on 30-second bins between the 2 systems was 82 +/- 7%. CONCLUSIONS: The WP_100 was reasonably accurate for unattended home diagnosis of OSA in a population sample not preselected for OSA symptoms. The current design, including simultaneous home PSG recordings in population-based cohorts, is proposed as a reasonable validation standard for assessment of simplified recording tools for OSA diagnosis.     

Complex sleep apnea syndrome: is it a unique clinical syndrome?

STUDY OBJECTIVES: Some patients with apparent obstructive sleep apnea hypopnea syndrome (OSAHS) have elimination of obstructive events but emergence of problematic central apneas or Cheyne-Stokes breathing pattern. Patients with this sleep-disordered breathing problem, which for the sake of study we call the "complex sleep apnea syndrome," are not well characterized. We sought to determine the prevalence of complex sleep apnea syndrome and hypothesized that the clinical characteristics of patients with complex sleep apnea syndrome would more nearly resemble those of patients with central sleep apnea syndrome (CSA) than with those of patients with OSAHS. DESIGN: Retrospective review SETTING: Sleep disorders center. PATIENTS OR PARTICIPANTS: Two hundred twenty-three adults consecutively referred over 1 month plus 20 consecutive patients diagnosed with CSA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Prevalence of complex sleep apnea syndrome, OSAHS, and CSA in the 1-month sample was 15%, 84%, and 0.4%, respectively. Patients with complex sleep apnea syndrome differed in gender from patients with OSAHS (81% vs 60% men, p < .05) but were otherwise similar in sleep and cardiovascular history. Patients with complex sleep apnea syndrome had fewer maintenance-insomnia complaints (32% vs 79%; p < .05) than patients with CSA but were otherwise not significantly different clinically. Diagnostic apnea-hypopnea index for patients with complex sleep apnea syndrome, OSAHS, and CSA was 32.3 +/- 26.8, 20.6 +/- 23.7, and 38.3 +/- 36.2, respectively (p = .005). Continuous positive airway pressure suppressed obstructive breathing, but residual apnea-hypopnea index, mostly from central apneas, remained high in patients with complex sleep apnea syndrome and CSA (21.7 +/- 18.6 in complex sleep apnea syndrome, 32.9 +/- 30.8 in CSA vs 2.14 +/- 3.14 in OSAHS; p < .001). CONCLUSIONS: Patients with complex sleep apnea syndrome are mostly similar to those with OSAHS until one applies continuous positive airway pressure. They are left with very disrupted breathing and sleep on continuous positive airway pressure. Clinical risk factors don't predict the emergence of complex sleep apnea syndrome, and best treatment is not known.     

Endothelial dysfunction and C-reactive protein in relation with the severity of obstructive sleep apnea syndrome

STUDY OBJECTIVES: To investigate flow-mediated dilatation (FMD) and C-reactive protein (CRP) levels in patients with obstructive sleep apnea syndrome (OSAS) in relation with the severity of respiratory disturbances and hypoxemia. DESIGN: After subjects had completed nocturnal polysomnography, FMD was measured in the brachial artery, and blood samples were obtained to determine serum CRP levels. SETTING: Sleep laboratory in Seoul National University Bundang Hospital. PATIENTS: Ninety men: 22 normal controls, 28 subjects with mild to moderate OSAS, and 40 with severe OSAS. MEASUREMENTS AND RESULTS: FMD was found to be correlated with oxygen desaturation index (ODI), percentage of time below 90% O2 saturation, average O2 saturation, lowest O2 saturation, systolic blood pressure, apnea hypopnea index (AHI), and body mass index. In addition, CRP was correlated with body mass index, waist-to-hip ratio, neck circumference, diastolic pressure, average O2 saturation and percentage of time below 90% O2 saturation but not with AHI. Stepwise multiple regression showed that the ODI was a significant determinant of FMD (adjusted R2 = 10%, beta = -0.33, P < 0.01). In addition, body mass index (beta = 0.25, P < 0.05) and waist-to-hip ratio (beta = 0.21, P < 0.05) were found to be significantly correlated with CRP (adjusted R2 = 12%, P < 0.05), independently of other factors. There was no correlation between FMD and CRP. CONCLUSION: As a marker of nocturnal hypoxemia, ODI rather than AHI might better explain the relationship between OSAS and FMD. Because body mass index and waist-to-hip ratio were identified as risk factors of high serum CRP in OSAS, obesity should be considered when predicting cardiovascular complications in OSAS.     

Oropharyngeal collapse predicts treatment response with oral appliance therapy in obstructive sleep apnea

STUDY OBJECTIVES: To examine whether primary oropharyngeal collapse of the upper airway during sleep predicts treatment success with oral appliance therapy in patients with obstructive sleep apnea. DESIGN: Prospective physiologic study. SETTING: Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS: Twelve treatment-na?ve adult patients with obstructive sleep apnea (apnea-hypopnea index > or = 10/h and at least 2 of the following symptoms: snoring, fragmented sleep, witnessed apneas, or daytime sleepiness). INTERVENTION: Custom-made mandibular advancement splint (MAS). MEASUREMENTS AND RESULTS: A baseline diagnostic polysomnogram confirmed AHI > or = 10 per hour. During the following acclimatization period, a custom-made adjustable MAS was incrementally advanced until maximum comfortable mandibular protrusion was reached. A second polysomnogram with MAS in situ determined efficacy. Following a 1-week washout period, a final sleep study was performed using multisensor catheters (with and without MAS, in random order during the same night) to determine upper-airway closing pressures and the site or sites of upper-airway collapse. MAS resulted in significant improvements, mean +/- SEM, in AHI (22.0 +/- 2.6 vs 9.2 +/- 1.9/h, p < .01) and upper-airway closing pressures during stage 2 non-rapid eye movement sleep (-1.1 +/- 0.3 vs -2.8 +/- 0.5 cm H2O, p < .01). All 4 patients with primary oropharyngeal collapse achieved an AHI < 5 per hour. Only 1 of the 8 patients with primary velopharyngeal collapse achieved an AHI < 5 per hour. Oropharyngeal collapse, compared with velopharyngeal collapse, predicted treatment success with MAS (p < .02). CONCLUSIONS: These preliminary data suggest that primary oropharyngeal collapse of the upper airway during sleep is an important predictor of treatment outcome with MAS therapy.     

Social inequalities in sleep‐disordered breathing: Evidence from the CoLaus|HypnoLaus study

Sleep‐disordered breathing is a common condition, related to a higher cardiometabolic and neurocognitive risk. The main risk factors for sleep‐disordered breathing include obesity, craniofacial characteristics, male sex and age. However, some studies have suggested that adverse socioeconomic circumstances and lifestyle‐related behaviours such as smoking and alcohol use, may also be risk factors for sleep‐disordered breathing. Here, we investigate the associations between socioeconomic status and sleep‐disordered breathing, as measured by sleep apnea–hypopnea and oxygen desaturation indexes. Furthermore, we assess whether these associations are explained by lifestyle‐related factors (smoking, sedentary behaviour, alcohol use and body mass index [BMI]). We used data from the CoLaus|HypnoLaus study, a population‐based study including 2162 participants from Lausanne (Switzerland). Socioeconomic status was measured through occupation and education. Sleep‐disordered breathing was assessed through polysomnography and measured using the apnea–hypopnea index (AHI: number of apnea/hypopnea events/hr: ≥15/≥30 events), and the ≥3% oxygen desaturation index (ODI: number of oxygen desaturation events/hr: ≥15/≥30 events). Lower occupation and education were associated with higher AHI and ODI (occupation: AHI30, odds ratio (OR) = 1.88, 95% confidence interval (CI) [1.07; 3.31]; ODI30, OR = 2.29, 95% CI [1.19; 4.39]; education: AHI30, OR = 1.21, 95% CI [0.85; 1.72]; ODI30, OR = 1.26, 95% CI [0.83; 1.91]). BMI was associated with socioeconomic status and AHI/ODI, and contributed to the socioeconomic gradient in SDB, with mediation estimates ranging between 43% and 78%. In this Swiss population‐based study, we found that low socioeconomic status is a risk factor for sleep‐disordered breathing, and that these associations are partly explained by BMI. These findings provide a better understanding of the mechanisms underlying social differences in sleep‐disordered breathing and may help implement policies for identifying high‐risk profiles for this disorder.     

Effect of 2000 m descent simulated in a hyperbaric chamber on arterial blood oxygen saturation and sleep quality in workers of a gold mine situated at an altitude of 3800-4200 m above sea level

Acute mountain sickness can become life threatening to people traveling at high altitude. Simulated descent with a hyperbaric chamber is a widely accepted way to treat this condition. The aim of this study was to analyze the influence of simulated descent to 2000 m on arterial oxygen saturation (SaO2), periodic breathing and sleep quality in a group of workers of a gold mine situated at 3800 m. Sleep studies were performed twice in stationary hyperbaric chamber with a portable system--MESAM IV in 20 workers. During the first study the chamber was not pressurized and on the second night the barometric pressure was set to mimic descent to 2000 m. During second study, a significant decrease in ODI (Oxygen Desaturation Index), from 9.7 +/- 6/h to 1.8 +/- 3.4/h (p < 0.0001), was noticed; mean SaO2 increased from 84.3 +/- 3.2% do 92.7 +/- 2.8% (p < 0.0001), significant changes in percentage of study time in individual SaO2 ranges were also noticed. The number (12.7 +/- 8.4 vs. 7.5 +/- 5; p < 0.05) and index of changes in body position were decreased (2.0 +/- 1.5 vs. 1.2 +/- 0.9/h; p < 0.05) as well. CONCLUSION: Simulated descent to 2000 m causes a decrease in number of desaturations, improvement in mean SaO2 during sleep, decrease in heart rate and these data suggest a decrease in periodic breathing during sleep. A decrease in number and index of body position changes suggests improved sleep quality.     

Atrial natriuretic excretion in patients with obstructive sleep apnea syndrome (OSAS)

During obstructive sleep apneas stimuli, that may increase excretion of atrial natriuretic peptide (ANP) occur. The aim of the study was the evaluation whether in patients with OSAS levels of ANP are significantly different in relation to sleep or wakefulness and in relation to disturbances of ventilation during sleep and wakefulness. The material of the study consisted of 34 patients with OSAS (age 25-65 years). There were no differences in the levels of ANP late in the evening, during sleep and early in the morning. There were 2 groups of the patients: with low (< 70 pg/ml, mean at 21 p.m. 9.7 +/- 8.7 pg/ml, at. 2 a.m. 12.5 +/- 9.3 pg/ml, at 6 a.m. 14.4 +/- 15.1 pg/ml) and high (> 70 pg/ml, mean at 21 p.m. 148.6 +/- 232.9 pg/ml, at 2 a.m. 119.5 +/- 45.5 pg/ml, at 6 a.m. 164.9 +/- 161 pg/ml) ANP levels. As compared with patients with low ANP levels, patients with high ANP levels were older and more obese, more frequently had concomitant COPD, lower VC and FEV1, higher daytime PaCO2 and lower PaO2; most of them had peripheral edema. In patients with high ANP levels there was more profound mean arterial blood desaturation during sleep apnoeas than in patients with low ANP levels (SaO2 75 +/- 8% vs 81 +/- 4%, p < 0.001), although apnea index and mean apnea duration were similar in both groups. CONCLUSIONS: In patients with OSAS the daytime and sleep levels of ANP are similar. High levels of ANP can be found in OSAS patients with impaired daytime ventilation and gas exchange, and profound arterial oxygen desaturation during sleep apnoeas.