Continuous positive airway pressure therapy decreases evening cortisol concentrations in patients with severe obstructive sleep apnea

Patients with obstructive sleep apnea syndrome (OSAS) show recurrent episodes of nightly hypoxic stress. The purpose of this study is the detection of alterations of the hypothalamic-pituitary-adrenal stress axis in OSAS patients before and after continuous positive airway pressure (CPAP) therapy. An activation of the hypothalamic-pituitary-adrenal axis was proposed because of the nightly hypoxic stress in these patients, but previous studies were not conclusive. Here we hypothesize that CPAP therapy decreases salivary cortisol concentrations in patients with severe OSAS. We performed a clinical within-subject study including 50 patients with newly diagnosed OSAS and an apnea-hypopnea index greater than or equal to 40 h⁻¹. Diurnal profiles of salivary cortisol concentrations were compiled before and after 3 months of treatment with CPAP. Therefore, 6 cortisol samples were collected: before and after lunch, in the evening, the next morning after awakening, and before and after breakfast. Thirty-eight patients returned after 3 months of CPAP therapy for follow-up. According to the reference range for healthy subjects, cortisol values were not pathologically increased. Analysis of variance revealed a significant effect of CPAP therapy on diurnal cortisol profiles (P = .048). Subjects with severe OSAS showed a decrease (3.04 ± 0.55 nmol L⁻¹ pre-CPAP vs 2.48 ± 0.78 nmol L⁻¹ post-CPAP, P = .038) of evening cortisol levels after CPAP treatment, whereas prelunch levels were increased after CPAP therapy (7.18 ± 0.83 nmol L⁻¹ pre-CPAP vs 10.22 ± 1.10 nmol L⁻¹ post-CPAP, P = .044). Our results show that CPAP therapy decreases evening cortisol concentrations in patients with severe OSAS. These data suggest that OSAS may increase the cortisol nadir that is reversed after CPAP therapy.     

Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome

The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea-hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 +/- 4.20 baseline versus 6.79 +/- 4.91 micromol/kg.min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m2 than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.     

Continuous positive airway pressure treatment improves pulmonary hemodynamics in patients with obstructive sleep apnea.

Daytime pulmonary hypertension (PH) is relatively common in obstructive sleep apnea (OSA) and is thought to be associated with pulmonary vascular remodeling (PRm). The extent to which PH is reversible with treatment is uncertain. To study this, we measured pulmonary hemodynamics (Doppler echocardiography) in 20 patients with OSA (apnea-hypopnea index [AHI] 48.6 +/- 5.2/h, mean +/- SEM) before and after 1 and 4 mo of CPAP treatment (compliance 4.7 +/- 0.5 h/night). Patients had normal lung function, and no cardiac disease or systemic hypertension. Doppler studies were performed at three levels of inspired oxygen concentration (11%, 21%, and 50%) and during incremental increases in pulmonary blood flow (10, 20, and 30 microg/kg/min dobutamine infusions). Treatment resulted in a decrease in pulmonary artery pressure (Ppa, 16.8 +/- 1.2 mm Hg before CPAP versus 13.9 +/- 0.6 mm Hg after 4 mo CPAP, p < 0.05) and total pulmonary vascular resistance (231.1 +/- 19.6 versus 186.4 +/- 12.3 dyn. s. cm(-)(5), p < 0.05). The greatest treatment effects occurred in the five patients who were pulmonary hypertensive at baseline. The pulmonary vascular response to hypoxia decreased after CPAP (DeltaPpa/DeltaSa(O(2)) 10.0 +/- 1.6 mm Hg before versus 6.3 +/- 0.8 mm Hg after 4 mo CPAP, p < 0.05). The curve of Ppa versus cardiac output (Q), derived from the incremental dobutamine infusion, shifted downward in a parallel fashion during treatment. Systemic diastolic blood pressure also fell significantly. Improvements in pulmonary hemodynamics were not attributable to changes in left ventricular diastolic function or Pa (O(2)). We conclude that CPAP treatment reduces Ppa and hypoxic pulmonary vascular reactivity in OSA and speculate that this may be due to improved pulmonary endothelial function.     

连续气道正压通气对阻塞性睡眠呼吸暂停患者血管内皮功能的影响

目的检测阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者血清一氧化氮（NO）、内皮素-1（ET-1）、血管性血友病因子（vWF）及肱动脉内径变化;评估连续气道正压通气（CPAP）对此类患者血管内皮功能的影响。方法选择OSAHS患者55例和健康对照组55例,分别测定所有受试者血清NO、ET-1、vWF水平,同时使用多普勒彩超测定肱动脉内径变化。对OSAHS患者使用CPAP治疗3月后再次测定以上指标。结果治疗前OSAHS患者血清NO水平和肱动脉内径变化率明显低于对照组（P均〈0．01）;血清ET-1和vWF水平明显高于对照组（P均〈0．01）。NO水平和肱动脉内径变化率与呼吸紊乱指数呈显著负相关（r分别为-0．621,-0．581,P〈0．01）,与最低血氧饱和度正相关（r分别为0．516,0．613,P〈0．01）;ET-1和vWF水平与呼吸紊乱指数呈正相关（r分别为0．534,0．559,P均〈0．01）,与最低血氧饱和度均呈负相关（r分别为-0．479,-0．637,P均〈0．01）。肱动脉内径变化率与NO呈正相关,与ET-1和vWF水平呈负相关（r分别为0．681,-0．541和-0．513,P均〈0．01）。结论OSAHS患者早期已存在血管内皮功能损害,与呼吸紊乱指数和低氧相关;CPAP能够改善患者血管内皮功能。     

持续气道内正压治疗阻塞性睡眠呼吸暂停低通气综合征

持续气道内正压（CPAP）通气是治疗阻塞性睡眠呼吸暂停低通气综合征（OSAHS）的主要方法。OSAHS患者经CPAP治疗后嗜睡改善、血压下降、心脑血管病变的发生率降低，生活质量提高。CPAP治疗OSAHS的主要机制是气道内正压使上气道撑开^[1]，并且由于呼气时气道内正压使肺残气增高，也有助于维持上气道的畅通。     

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea

OBJECTIVES: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). DESIGN AND METHODS: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP. RESULTS: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.9 (3.5, 4.8) to 6.2 (4.6, 26.2) ms/mmHg, P<0.05]. Increases in the slope of BRS persisted following withdrawal of CPAP [4.9 (4.3, 6.9) ms/mmHg, P<0.05]. CPAP also lowered heart rate (from 81.3 +/- 4.9 to 76.0 +/- 5.7 bpm, P< 0.05), an effect which persisted after its withdrawal (76.7 +/- 5.7 bpm, P < 0.05). Systolic blood pressure at the midpoint of the pressure range of BRS sequences fell while on CPAP (from 139 +/- 8 to 120 +/- 7 mmHg, P < 0.05), and remained lower following CPAP withdrawal (124 +/- 9 mmHg, P < 0.05). CONCLUSIONS: In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.     

CPAP对高原地区OSAHS患者氧化应激的干预作用

目的探讨持续气道正压(CPAP)通气对高原阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者氧化应激的干预作用。方法对42例高原OSAHS患者监测了AHI、MSaO2、T80。在睡前、晨起及CPAP治疗6周晨起分别测血清8-iso-PGF2α、SOD、MDA、T-AOC,并与30例健康组比较。结果 OSAHS组睡前血清8-isoPGF2α、MDA显著高于,SOD、T-AOC显著低于健康组(均P<0.01);OSAHS组晨起血清8-isoPGF2α、MDA显著高于,SOD、T-AOC显著低于睡前(均P<0.01);治疗前,AHI、T80与晨起血清8-isoPGF2α、MDA显著正相关,与血清SOD、T-AOC显著负相关(均P<0.01);MSaO2与8-isoPGF2α、MDA显著负相关,与SOD、T-AOC显著正相关(均P<0.01)。OSAHS组治疗后晨起与治疗前晨起比较,血清8-isoPGF2α、MDA显著降低,SOD、T-AOC显著升高(均P<0.01)。结论高原OSAHS患者存在持续性氧化应激,晨起较睡前严重,且与病情程度有显著相关性。CPAP通气治疗能有效地改善OSAHS患者氧化应激。     

Salivary markers of oxidative stress in patients with obstructive sleep apnea treated with continuous positive airway pressure

Purpose

Obstructive sleep apnea syndrome (OSAS) is characterized by elevated oxidative stress. Measurement of oxidative stress in saliva seems to be promising in long-term treatment monitoring of OSAS patients. In this study, our aim was to investigate whether short-term continuous positive airway pressure (CPAP) treatment would influence oxidative stress in saliva.

Methods

Patients with diagnosed OSAS (16 women, 28 men) underwent polysomnography during the first night and CPAP treatment during the second night. Saliva samples were taken in the evening and morning on both days. Markers of oxidative stress and antioxidant status were analyzed in saliva.

Results

Evening concentrations of the salivary thiobarbituric acid reacting substances (p?p?p?Conclusion Salivary markers of oxidative stress and antioxidant status do not change significantly after one night treatment with CPAP. On the contrary, after 1 month with CPAP therapy, reduced markers of oxidative stress were reported. Therefore, the future studies should be focused on finding the optimal sampling frequency to clarify the potential of saliva for the monitoring of OSAS treatment.     

Nasal continuous positive airway pressure therapy in obstructive sleep apnea syndrome]

Sixteen patients (male: 14, female: 2, 41-72 yrs, mean 57.5 yrs) with OSAS were treated by nCPAP in our hospital since 1987. Respiratory disturbance index ranged from 16.5 to 83.1. The longest apnea duration was 35.0-120.5 seconds before the treatment. Two patients were treated with Sleep Easy III (Respironics Inc.) and others with a home made instruments. nCPAP was set at a pressure of 5 to 10 cm H2O. 12 patients (75%) tolerated the device but 4(25%) did not. Polysomnographic parameters before and after nCPAP therapy were compared. The longest apnea duration was 63.1 +/- 23.5 to 40.9 +/- 27.4 seconds (P less than 0.001) and the lowest saturation oxygen was 55.1 +/- 20.4% to 71.4 +/- 18.6% (P less than 0.05). The sleep structure improved but not significant statistically. One of them used nCPAP at home for more than two. years and showed a good long term effect. We concluded that nCPAP is an effective and safe treatment for OSAS. However, patients may be uncomfortable because of the wearing of the nasal mask during sleep.     

Continuous positive airway pressure treatment improves baroreflex control of heart rate during sleep in severe obstructive sleep apnea syndrome

The role of the arterial baroreflex in the cardiovascular changes associated with the obstructive sleep apnea syndrome (OSAS), and the effect of nasal continuous positive airway pressure (CPAP) treatment on baroreflex function during sleep are unknown. Baroreflex control of heart rate was studied in 29 normotensive patients with OSAS under no treatment, in 11 age-matched control subjects, and in 10 patients at CPAP withdrawal after 5.5 +/- 3.7 (range 3-14) months of treatment. Baroreflex control of heart rate was assessed by "sequence method" analysis of continuous blood pressure recordings (Finapres) obtained during nocturnal polysomnography. In untreated OSAS, baroreflex sensitivity (BRS) was low during wakefulness and non-rapid eye movement (REM) stage 2 sleep compared with control subjects, and correlated inversely with mean lowest Sa(O(2)) and the blood pressure increase after apneas. After CPAP treatment, the apnea-hypopnea index was lower, and mean lowest Sa(O(2)) higher than before treatment. After CPAP, patients were more bradycardic, blood pressure and its standard deviation decreased as Sa(O(2)) improved in non-REM stage 2 sleep, and BRS increased (nocturnal wakefulness: +59%; non-REM stage 2 sleep: +68% over pretreatment values). Our data suggest that baroreflex dysfunction in OSAS may be at least partly accounted for by nocturnal intermittent hypoxemia, and can be reversed by long-term CPAP treatment.     

Continuous positive airway pressure improves daytime baroreflex sensitivity and nitric oxide production in patients with moderate to severe obstructive sleep apnea syndrome.

Individuals with obstructive sleep apnea syndrome (OSAS) are at high risk for cardiovascular morbidity and mortality. The effects of OSAS severity and nocturnal continuous positive airway pressure (CPAP) on daytime baroreflex sensitivity (BRS) and nitric oxide (NO) production were investigated in OSAS patients. Fifty-one consecutive males with OSAS and 29 age-matched healthy men underwent the Valsalva test and standard polysomnography. Patients with an apnea-hypopnea index (AHI) of >or=20 episodes per hour were randomized to receive CPAP treatment for 3 months (n=14) or no such treatment (n=19). The BRS index measured from the overshoot phase (phase IV) of the Valsalva maneuver and plasma NO concentration were significantly lower, whereas the AHI, oxygen desaturation time, arousal index, percentage of sleep stage 1, and systolic blood pressure were significantly greater, in patients with an AHI of >or=20/h than in those with an AHI of <20/h or in controls. The 24-h urinary excretion of norepinephrine was significantly reduced and the plasma NO concentration was significantly increased after one night of CPAP. The BRS index for phase IV and the Valsalva ratio were significantly increased in the CPAP group after the 3-month treatment period but remained unchanged in the non-CPAP group of OSAS patients. The daytime BRS index and NO production were thus inversely related to the severity of OSAS, and successful CPAP treatment improved these parameters in patients with moderate to severe OSAS. CPAP may therefore reduce the risk of cardiovascular complications due to endothelial dysfunction or increased sympathetic activity.     

连续气道正压通气对男性阻塞性睡眠呼吸暂停患者自主神经调制的影响

目的 探讨连续气道正压通气(CPAP)对阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者自主神经调制的影响.方法 选择OSAHS患者60例和对照组25例,对所有受试者进行多导睡眠图及动态心电图监测,采用时域分析法分析患者心率变异性以评价自主神经调制功能.对OSAHS患者使用CPAP治疗3个月后再次评估自主神经调制功能.结果 与对照组相比,OSAHS组自主神经调制功能指标正常RR间期标准差(SDNN)、RR间期差值均方根(rMSSD)、每5分钟节段平均正常RR间期标准差(SDANN)和高频功率(HF)均低于对照组,且与呼吸紊乱指数呈负相关;低频功率(LF)和低频与高频之比(LF/HF)高于对照组,与呼吸紊乱指数呈正相关.LF/HF值与呼吸紊乱指数和最低血氧饱和度呈线性回归关系.结论 OSAHS患者存在自主神经调制功能损害,与呼吸紊乱指数和低氧有关;经CPAP治疗后,OSAHS患者自主神经调制功能损害明显改善,且对CPAP耐受良好.     

Arbitrary-pressure continuous positive airway pressure for obstructive sleep apnea syndrome

Current resources are inadequate to meet the demand for polysomnography, resulting in long waiting lists. This study aimed to evaluate the role of arbitrary-pressure continuous positive airway pressure (CPAP) as a method to reduce delays in commencing treatment. The study was of an open, randomized, parallel design. Ninety-one subjects with obstructive sleep apnea syndrome were randomized to either arbitrary-pressure CPAP based on body mass index before treatment polysomnography or to CPAP at settings determined by polysomnography. Both interventions resulted in similar improvements in clinical outcomes as determined by Epworth Sleepiness Score, Short Form-36 Quality of Life questionnaire, objective compliance, and subjective attitudes to treatment. There was higher sleep efficiency at treatment polysomnography in the group commenced at arbitrary pressure (81.8 +/- 10.1% [mean +/- SD] compared with 72.2 +/- 18.0%, p = 0.01). Subjects unable to tolerate CPAP were identified by the use of arbitrary pressure, leading to a reduction in the proportion of "wasted" treatment polysomnograms (studies performed in subjects not persisting with treatment) relative to commencing therapy after treatment polysomnography (3 of 39 compared with 12 of 35, p = 0.01). This approach to initiating treatment with CPAP appears feasible when there are long waiting lists for polysomnography.     

Effect of continuous positive airway pressure therapy on 24-hour blood pressure in patients with obstructive sleep apnea syndrome

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) are subject to an increased cardiovascular morbidity including systemic hypertension. Little is known about the effects of treatment with nasal continuous positive airway pressure (CPAP) on systemic hypertension. METHODS: Automated ambulatory 24-h blood pressure (BP) monitoring was performed in 88 consecutive patients who were referred for evaluation of snoring or suspected OSAS. In addition, the long-term effects of CPAP therapy on 24-h BP were assessed. RESULTS: A total of 62 patients had OSAS and 26 habitual snoring. Patients with OSAS had significantly higher mean arterial BP values than snorers (102.7 +/- 10.7 v 94.0 +/- 10.2 mm Hg; P < .01). Multiple stepwise linear regression analysis disclosed that the degree of systemic hypertension was independently associated with the severity of OSAS as determined by the apnea/hypopnea index (R = 0.43; P < .001), but not with age, body mass index, or smoking habits. Of the 62 patients with OSAS, 52 were treated with CPAP and reevaluated after 9 months. The CPAP resulted in a significant decrease in mean arterial BP (from 103.7 +/- 10.4 to 99.1 +/- 10.8 mm Hg; P < .05). For those patients with systemic hypertension whose BP improved with CPAP therapy, 24-h mean pulse pressure at baseline (r = -0.36; P < .05) as well as average heart rate during the day (r = -0.35; P < .05) turned out as predictors. CONCLUSIONS: Obstructive sleep apnea syndrome contributes, at least in part, to the development of systemic hypertension, and CPAP may improve BP values in treated OSAS patients. Predictors of a beneficial CPAP effect on BP are a high heart rate and a high pulse pressure before treatment.