Effect of continuous positive airway pressure and placebo treatment on sympathetic nervous activity in patients with obstructive sleep apnea

STUDY OBJECTIVES: We studied the effect of continuous positive airway pressure (CPAP) treatment on sympathetic nervous activity in 38 patients with obstructive sleep apnea. DESIGN: Randomized, placebo-controlled trial. SETTING: Patients underwent polysomnography on three occasions in a clinical research center, and had BP monitored over 24 h at home. All of the patients had sleep apnea with a respiratory disturbance index (RDI) > 15. INTERVENTIONS: The patients were randomized blindly to CPAP or placebo (CPAP at ineffective pressure) treatment. Measurements and results: Prior to therapy, the number of apneas and the severity of nocturnal hypoxia correlated significantly with daytime urinary norepinephrine (NE) levels, but not nighttime urinary NE levels. CPAP treatment lowered daytime BP from 99 +/- 2 mm Hg to 95 +/- 3 mm Hg (mean +/- SEM) and nighttime BP from 93 +/- 3 mm Hg to 88 +/- 3 mm Hg. Placebo CPAP treatment decreased both day and night mean BP only 2 mm Hg. CPAP, but not placebo, treatment lowered daytime plasma NE levels by 23%, daytime urine NE levels by 36%, daytime heart rate by 2.6 beats/min, and increased lymphocyte beta(2)-adrenergic receptor sensitivity (all p < 0.05). The effect of CPAP treatment on nighttime urine NE levels and heart rate did not differ from placebo treatment. There was a suggestion of an effect of placebo CPAP treatment on nighttime measures, but not on daytime measures. CONCLUSION: We conclude that daytime sympathetic nervous activation is greater with more severe sleep apnea. CPAP treatment diminished the daytime sympathetic activation; the potential nighttime effect of CPAP treatment was obscured by a small placebo effect.     

Nocturnal continuous positive airway pressure decreases daytime sympathetic traffic in obstructive sleep apnea

BACKGROUND: Patients with obstructive sleep apnea (OSA) have high levels of muscle sympathetic nerve activity (MSNA). We tested the hypothesis that long-term continuous positive airway pressure (CPAP) treatment will decrease MSNA in OSA patients. METHODS AND RESULTS: We measured blood pressure, heart rate, and MSNA in 11 normotensive, otherwise healthy patients with OSA who were treated with CPAP. The measurements were obtained at baseline and after 1 month, 6 months, and 1 year of CPAP treatment. These measurements were compared with those recorded in 9 otherwise healthy OSA patients who were not treated with CPAP for 1 year. In both untreated and treated patients, blood pressure and heart rate did not change over time. MSNA was similar during repeated measurements in the untreated group. By contrast, MSNA decreased significantly over time in patients treated with CPAP. This decrease was evident after both 6 months and 1 year of CPAP treatment (P=0.02 for both). CONCLUSIONS: CPAP treatment decreases muscle sympathetic traffic in patients with OSA. This effect of CPAP is evident only after an extended duration of therapy.     

Prediction of continuous positive airway pressure in obstructive sleep apnea

Continuous positive airway pressure (CPAP) prediction formulas can potentially simplify the treatment of obstructive sleep apnea (OSA). However, they can be difficult to derive and validate. We tested a statistical method to derive and validate a CPAP prediction formula using the same sample population. Seventy-six OSA patients underwent polysomnography and CPAP titration. Anthropometric measures, sleep parameters, and the Epworth sleepiness scale (ESS) were evaluated as predictors. All subsets regression was used to determine the optimum number of variables in the model. The Bayes information criterion was used to find the best-fit model. The model was then evaluated by a tenfold cross-validation procedure. Subjects were obese (BMI 31.3 ± 5.4) and had significant daytime somnolence (ESS 11.9 ± 5). Mean respiratory disturbance index (RDI) was 53.5 ± 31.3. The ESS was not predictive of titrated CPAP. The best-fit model included three variables (CPAP_pred = 30.8 + RDI × 0.03 − nadir saturation × 0.05 − mean saturation × 0.2). This model explained 67% of the variance. Our data and the literature suggest that a combination of two to three factors is predictive of titrated CPAP: RDI, oxyhemoglobin saturation, and obesity. Except for RDI, the specific factors vary in each population. A CPAP prediction formula that explains a high proportion of the titrated CPAP variance can be easily derived from parameters measured during the diagnostic work-up of OSA patients using a unique statistical model that allows derivation and validation of the formula in the same test population.     

Effect of continuous positive airway pressure vs placebo continuous positive airway pressure on sleep quality in obstructive sleep apnea

STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) therapy has become the treatment of choice for obstructive sleep apnea (OSA). However, the efficacy of CPAP therapy has not been evaluated against a suitable control. We investigated the effectiveness of CPAP therapy in improving sleep quality in patients with OSA. We hypothesized that CPAP improves sleep quality. PATIENTS: Forty-eight CPAP-naive OSA patients were evaluated. None were receiving antihypertensive medications, and none had major medical illnesses. DESIGN: Patients were randomized to receive either CPAP or placebo CPAP (CPAP at an ineffective pressure) for 7 days in a double-blind fashion. Forty-one patients completed the protocol. Sleep quality variables, arousals, sleep arterial oxygen saturation (SaO(2)), and respiratory disturbance index (RDI) were assessed at baseline, after 1 day of treatment, and after 7 days of treatment. Repeated measures analysis of variance was used to evaluate the effects of treatment, time, and the interaction of the two. RESULTS: As expected, CPAP lowered RDI and number of arousals, and increased SaO(2) over time (p = 0.001). Contrary to expectations, both CPAP and placebo CPAP had comparable effects on sleep quality as assessed by sleep architecture, sleep efficiency, total sleep time, and wake after sleep onset time. CONCLUSIONS: This study confirms the effectiveness of CPAP in lowering the number of arousals and the RDI, and in raising SaO(2). However, our data suggest that short-term CPAP is no different than placebo in improving sleep architecture. Further evaluation of the effectiveness of CPAP using a suitable placebo CPAP in prospective randomized studies is needed     

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.     

Long-term acceptance of continuous positive airway pressure in obstructive sleep apnea

We studied the long-term acceptability of nasal continuous positive airway pressure (CPAP) treatment in 168 consecutive patients, 147 with obstructive sleep apnea (OSA) and 21 with snoring. Follow-up was between 1.5 and 78 months. At latest follow-up 107 of 168 (64%) were still using CPAP. Acceptance of CPAP was least for patients with snoring alone (6 of 21 persisted) and best for patients with both excessive daytime somnolence and severe hypoxemia (minimum SaO2 less than 75%), of whom 40 of 45 (89%) persisted with treatment. Patients with excessive daytime somnolence but without severe hypoxemia were less tolerant of CPAP (39 of 71, 55%, persisted) than patients with no symptoms of excessive somnolence but with severe hypoxemia (21 of 30, 70%, persisted). The most common reasons for discontinuing CPAP were intolerance of the mask (26 of 61), the inconvenience of treatment (16 of 61), and the lack of symptomatic benefit from treatment (10 of 61). We concluded that long-term acceptance of CPAP was difficult to predict in advance but that it was most likely in patients with the most severe sleep apnea. Because intolerance of the mask and inconvenience were the most common reasons for ceasing treatment, improvements in the design of CPAP systems and careful patient training may improve the acceptability of CPAP substantially.     

经鼻持续气道正压通气对阻塞性睡眠呼吸暂停综合征的综合疗效

经鼻持续气道正压通气（CPAP）是目前治疗阻塞性呼吸暂停综合征（OSAS）最有效的内科治疗方法,通过向气道内增加一定程度的正压,保持上气道通畅,消除患者夜间缺氧,改善患者夜间打鼾,白天嗜睡等临床症状,恢复睡眠结构,并治疗与此相关的各系统疾病,提高患者长期的生活质量。     

Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea

Previous studies have demonstrated that lung volume during wakefulness influences upper airway size and resistance, particularly in patients with sleep apnea. We sought to determine the influence of lung volume on the level of continuous positive airway pressure (CPAP) required to prevent flow limitation during non-REM sleep in subjects with sleep apnea. Seventeen subjects (apnea-hypopnea index, 42.6 +/- 6.2 [SEM]) were studied during stable non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. An epiglottic pressure catheter plus a mask/pneumotachometer were used to assess flow limitation. When lung volume was increased by 1,035 +/- 22 ml, the CPAP level could be decreased from 11.9 +/- 0.7 to 4.8 +/- 0.7 cm H(2)O (p < 0.001) without flow limitation. The decreased CPAP at the same negative extrathoracic pressure yielded a final lung volume increase of 421 +/- 36 ml above the initial value. Conversely, when lung volume was reduced by 732 +/- 74 ml (n = 8), the CPAP level had to be increased from 11.9 +/- 0.7 to 17.1 +/- 1.0 cm H(2)O (p < 0.001) to prevent flow limitation, with a final lung volume decrease of 567 +/- 78 ml. These results demonstrate that relatively small changes in lung volume have an important effect on the upper airway in subjects with sleep apnea during non-REM sleep.     

CPAP治疗对阻塞型睡眠呼吸暂停患者血压变异性的影响

目的:探讨经鼻持续正压通气(nCPAP)治疗对阻塞性睡眠呼吸暂停综合征(OSAHS)患者血压变异性的影响. 方法:采用24 h动态血压监测与多导睡眠(PSG)同步监测的方法,对102例OSAHS受试者按睡眠呼吸暂停紊乱指数(AHI)分为正常对照组、轻度组和中重度组,观察3组患者的血压情况；对中重度组加用nCPAP治疗后,再观察各项指标的改变. 结果:中重度组患者的平均血压水平均高于对照组及轻度组(P＜0.01)；中重度组患者经nCPAP治疗8周后,血压变异性包括晨峰现象、非杓型血压比例均较治疗前有明显下降(P＜0.05). 结论:OSAHS患者的血压有特征性变化,中重度患者接受有效的nCPAP治疗后,不仅纠正了呼吸障碍,也改善了血压变异性及晨峰现象.     

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.     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Blood pressure and sleep apnea: results of long-term nasal continuous positive airway pressure therapy

Arterial blood pressure patterns in 12 men with sleep apnea and arterial hypertension were studied at baseline and after 6 months' therapy with nasal continuous positive airway pressure (nCPAP). Preexisting antihypertensive medication was discontinued 1 week before baseline measurements. Weight did not change during the study period; body mass index was 29.3 (range, 25.4-38.5) vs. 29.3 (25.0-38.5). During therapy the apnea index decreased from 58 (range 30-73) to 2 (range 0-7) apneic episodes per hour (p less than 0.01). Intra-arterial systolic (BP sys.) and diastolic (BP dias.) blood pressure and heart rate decreased during therapy (p less than 0.001). Mean values +/- 95% confidence intervals were as follows: BP sys., 147.1 (+/- 1.6) mm Hg vs. 126.4 (+/- 1.5) mm Hg; BP dias., 81.6 (+/- 0.8) mm Hg vs. 69.4 (+/- 0.6) mm Hg; heart rate, 68.8 (+/- 0.7) beats/min vs. 65.4 (+/- 0.7) beats/min. Furthermore, the variability of these parameters decreased during therapy: variability BP sys., 53.8 (+/- 1.1) mm Hg vs. 25.6 (+/- 1.1) mm Hg; variability BP dias., 35.6 (+/- 0.7) mm Hg vs. 17.9 (+/- 0.7) mm Hg; variability of heart rate, 28.1 (+/- 0.7) beats/min vs. 14.9 (+/- 0.7) beats/min (p less than 0.001). During treatment we found that blood pressure scores already dropped during the awake phase, with a further decrease during non-REM and REM sleep (p less than 0.001). Our results, which demonstrate the reversibility of high blood pressure upon treatment of sleep apnea, indicate that sleep apnea can be an etiological factor in hypertension. Sleep apnea should therefore be considered in the differential diagnosis of arterial hypertension.     

Efficacy of continuous positive airway pressure on arrhythmias in obstructive sleep apnea patients

The purpose of this study was to determine the relationship between obstructive sleep apnea (OSA) and cardiovascular disorders in a large Japanese population, and to assess the efficacy of continuous positive airway pressure (CPAP) in the treatment of OSA-associated arrhythmias. The study population comprised 1394 Japanese subjects (1086 men and 308 women) who were divided into four groups on the basis of polysomnography (PSG) analysis as follows: the no sleep apnea (N-SA) group (n = 44, apnea-hypopnea index [AHI] < 5), the mild OSA (Mi-OSA) group (n = 197, 5 < AHI < 15), the moderate OSA (Mo) group (n = 368, 15 < AHI < 30), and severe OSA (SOSA) group (n = 785, AHI < 30). The following baseline characteristics were significantly associated with OSA: age (P < 0.001), gender (P < 0.001), body mass index (P < 0.001), hypertension (P < 0.001), diabetes (P = 0.009), and hyperlipidemia (P = 0.013). In the OSA group, PSG revealed the predominance of paroxysmal atrial fibrillation (PAF) (P = 0.051), premature atrial complex short run (P < 0.005), premature ventricular complex (PVC, P = 0.004), sinus bradycardia (P = 0.036), and sinus pause (arrest >2 s, P < 0.001) during the PSG recording. A total of 316 patients from the group underwent CPAP titration and were then re-evaluated. Continuous positive airway pressure therapy significantly reduced the occurrences of PAF (P < 0.001), PVC (P = 0.016), sinus bradycardia (P = 0.001), and sinus pause (P = 0.004). The results of this study demonstrate a significant relationship between OSA and several cardiac disorders, and also demonstrate the efficacy of CPAP in preventing OSA-associated arrhythmias in a large population of Japanese patients.     

阻塞性睡眠呼吸暂停患者持续正压通气治疗前后自主神经 …

目的 研究阻塞性睡眠呼吸暂停（ＯＳＡ）患者夜间睡眠时自主神经功能的状态，以及有效的持续正压通气治疗对自主神经张力的影响。方法 对５６例重度ＯＳＡ患者持续正压通气（ＣＰＡＰ）治疗前和治疗中进行夜间７小时多导睡眠图（ＰＳＧ）及动态心电图监测，另择３０名正常受试者作为对照。采用心率功率谱分析法（ＨＲＰＳＡ）定量分析ＯＳＡ患者治疗前后夜间自主神经功能的变化。结果 ＯＳＡ组夜间睡眠时伴随着反复的呼吸暂停和低     

The impact of continuous positive airway pressure on heart rate variability in obstructive sleep apnea patients during sleep: A meta-analysis

Background

Heart rate variability (HRV), modulated by cardiac autonomic function, is impaired in obstructive sleep apnea (OSA). However, the effect of continuous positive airway pressure (CPAP) on HRV is debated.

Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure

Obstructive sleep apnea (OSA) is highly prevalent among patients with congestive heart failure (CHF) and may contribute to progression of cardiac dysfunction via hypoxia, elevated sympathetic nervous system activity, and systemic hypertension. Our aim was to assess the long-term effect of OSA treatment with nocturnal continuous positive airway pressure (CPAP) on systolic heart function, sympathetic activity, blood pressure, and quality of life in patients with CHF. Fifty-five patients with CHF and OSA were randomized to 3 months of CPAP or control groups. End points were changes in left ventricular ejection fraction, overnight urinary norepinephrine excretion, blood pressure, and quality of life. Nineteen patients in the CPAP group and 21 control subjects completed the study. Compared with the control group, CPAP treatment was associated with significant improvements in left ventricular ejection fraction (delta 1.5 +/- 1.4% vs. 5.0 +/- 1.0%, respectively, p = 0.04), reductions in overnight urinary norepinephrine excretion (delta 1.6 +/- 3.7 vs. -9.9 +/- 3.6 nmol/mmol creatinine, p = 0.036), and improvements in quality of life. There were no significant changes in systemic blood pressure. In conclusion, treatment of OSA among patients with CHF leads to improvement in cardiac function, sympathetic activity, and quality of life.