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系统功能的研究

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氧血症，低频（ＬＦ）及高频（ＨＦ）值逐渐增高，与对照组比较差异有显著性（ＬＦ为１３８３±３０５∶１２５±６４，Ｐ＜０．００１；ＨＦ为６６２±１９０∶１６３±７８，Ｐ＜０．００１），表明交感神经和副交感神经张力均明显增高。夜间平均ＬＦ／ＨＦ比率在较高水平（２１１±１０１），与对照组（０８７±０６４）比较差异有显著性（Ｐ＜０．０５），说明以交感神经张力增加更为显著。经过有效的ＣＰＡＰ治疗，ＯＳＡ患者ＬＦ（２２１±８１）、ＨＦ（２２１±１０８）明显降低（Ｐ＜０．００１）。结论ＯＳＡ患者夜间有自主神经功能紊乱。针对ＯＳＡ的有效治疗可以改善自主神经的异常活动     

病情严重程度及经鼻持续正压通气对阻塞性睡眠呼吸暂停患者自主神经功能的影响

阻塞性睡眠呼吸暂停综合征 (ＯＳＡＳ)与心血管疾病 (高血压、冠心病、心力衰竭甚至夜间猝死等 )关系密切 ,研究睡眠中自主神经功能状态对理解其心血管系统神经调节的程度和方式具有重要意义[1] 。本文作者于 1999- 0 2～ 1999-0 5采用心率功率谱分析法[2 ] (ＨＲＰＳＡ)分析ＯＳＡＳ患者夜间清醒及睡眠时自主神经功能状态 ,比较病情严重程度及有效的经鼻持续正压通气 (ＮＣＰＡＰ)治疗对自主神经功能的影响。1　对象与方法对确诊为ＯＳＡＳ的患者按睡眠呼吸暂停低通气指数(ＡＨＩ)分为 3组 :轻度 (ＡＩＨ∶5～ 2 0 )、中度 (ＡＨＩ:2 1～ 5…     

阻塞性睡眠呼吸暂停患者睡眠时高血压的发生

目的明确阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）患者清醒及睡眠时血压变化情况及对其影响的相关因素。方法１３例ＯＳＡＳ患者在桡动脉内留置导管监测血压并同步进行夜间睡眠多导生理仪连续记录，部分患者观察吸氧或经鼻（面）罩持续正压通气（ＮＣＰＡＰ）的治疗效果。结果（１）ＯＳＡＳ患者白天高血压发生率为４６％（６／１３）；白天无高血压的患者夜间一过性高血压发生率为８６％（６／７）；（２）ＯＳＡＳ患者夜间血压增高与低氧血症和呼吸暂停时间有关，与呼吸暂停指数（ＡＩ）无相关性（Ｐ＞０．０５）；（３）２例ＯＳＡＳ患者经吸氧治疗后，夜间血压波动仍存在，高血压未得到纠正；４例ＯＳＡＳ患者经ＮＣＰＡＰ治疗后，夜间血压波动消失。结论白天无高血压的ＯＳＡＳ患者夜间可反复出现一过性血压增高；ＯＳＡＳ患者夜间血压增高与低氧血症、呼吸暂停时间有关，但低氧血症不是引起夜间血压增高的主要因素；单纯吸氧不能纠正ＯＳＡＳ患者夜间血压增高，ＮＣＰＡＰ是纠正ＯＳＡＳ患者夜间血压增高的较好方法。     

自动持续正压系统对睡眠呼吸障碍的诊治

目的探索简便、临床易于推广应用的睡眠呼吸障碍疾患的诊治手段。方法对１１例睡眠呼吸障碍患者同步进行经典的多导睡眠图监测和自动持续正压系统监测，将监测结果进行比较；对２３例已确诊的阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）患者使用自动持续正压系统治疗，并对治疗效果进行评价。各监测指标比较采用ｔ检验。结果（１）自动持续正压系统与多导睡眠图相比较，自动持续正压系统虽无睡眠及心电记录，但可记录鼾声及上气道阻力；最高及最低血氧饱和度、最长呼吸暂停时间、呼吸暂停低通气（ＡＨＩ）指数等监测结果，两者相比，差异无显著性（Ｐ＞０．０５）；自动持续正压系统诊断ＯＳＡＳ的敏感性为７０％，特异性为１００％。（２）ＯＳＡＳ患者使用自动持续正压系统治疗后症状改善；ＡＨＩ显著减低，最低血氧饱和度显著升高（Ｐ＜０．００１）；此外，平均和最高压力与９５％可信压力比较差异有显著性。结论自动持续正压系统使用简便，并减轻了技术员监测时的劳动强度；在持续正压通气（ＣＰＡＰ）治疗时可采用９５％可信限所需的压力     

经鼻持续气道内正压通气与咽手术治疗阻塞性睡眠呼吸暂停 …

目的 对比观察经鼻持续气道内正压通气（ＣＰＡＰ）与悬雍垂腭咽成形术（ＵＰＰＰ）治疗阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）的疗效及对睡眠呼吸参数的影响，评价二者在ＯＳＡＳ治疗中的地位。方法 ６０例ＯＳＡＳ患者，ＣＰＡＰ治疗组３６例，手术治疗组２４例，治疗前后作整夜多导睡眠图（ＰＳＧ）监测。结果 两线呼吸紊乱指数减少，夜间低氧血症改善，ＣＰＡＰ组患者优于手术组（Ｐ〈０．０１），有效率ＣＰＡＰ组为９７％。     

阻塞性睡眠呼吸暂停综合征患者持续正压通气治疗前后认知功能的研究

阻塞性睡眠呼吸暂停综合征 (ＯＳＡＳ)是以睡眠结构紊乱和反复发作低氧血症为特征的一种睡眠障碍性疾病 ,其脑功能损害以认知功能障碍最常见。经鼻罩持续气道内正压(ｎＣＰＡＰ)通气治疗ＯＳＡＳ是目前最佳选择。本研究应用ｎＣＰＡＰ治疗ＯＳＡＳ患者 ,观察其治疗前、后认知功能的变化。对象与方法　对 132例打鼾患者进行夜间 7ｈ多导睡眠图 (ＰＳＧ)监测。筛选出 2 0例中、重症患者 [呼吸紊乱指数 (呼吸暂停 /低通气指数 ,ＡＨＩ) >2 0 ],其中男 16例 ,女 4例。年龄 48～ 6 9岁。符合ＯＳＡＳ的诊断标准 :睡眠呼吸暂停为睡眠时鼻和口气流…     

持续气道正压通气治疗肺心病并睡眠呼吸暂停综合征11例疗效观察

慢性肺原性心脏病（ＣＰＨＤ）是严重的呼吸系疾病,常与睡眠呼吸暂停综合征（ＯＳＡＳ）共存,夜间睡眠出现低氧血症可促发肺动脉压升高,加重肺心病。近年来,我们对１１例ＣＰＨＤ并ＯＳＡＳ患者采用持续气道正压通气（ＣＰＡＰ）治疗,取得满意疗效。１　资料与方法本...     

经鼻持续气道内正压通气与咽手术治疗阻塞性睡眠呼吸暂停综合征对比观察

目的对比观察经鼻持续气道内正压通气（ＣＰＡＰ）与悬雍垂腭咽成形术（ＵＰＰＰ）治疗阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）的疗效及对睡眠呼吸参数的影响，评价二者在ＯＳＡＳ治疗中的地位。方法６０例ＯＳＡＳ患者，ＣＰＡＰ治疗组３６例，手术治疗组２４例。治疗前后作整夜多导睡眠图（ＰＳＧ）监测。结果两组呼吸紊乱指数减少，夜间低氧血症改善，ＣＰＡＰ组患者优于手术组（Ｐ＜０．０１）。有效率ＣＰＡＰ组为９７％，手术组为４６％（Ｐ＜０．０１），最长暂停时间ＣＰＡＰ组缩短，手术组改变不显著，１０例延长。结论ＣＰＡＰ疗效肯定，优于ＵＰＰＰ，适应证广，可作为ＯＳＡＳ首选治疗     

经鼻持续性气道正压对阻塞性睡眠呼吸暂停综合征患者呼吸中枢驱动性的影响

为了解经鼻持续性气道正压（ｎＣＰＡＰ）通气治疗对阻塞性睡眠呼吸暂停综合征（ＯＳＡＳ）患者呼吸中枢驱动性的影响，研究了２０例无二氧化碳（ＣＯ＿２）储留的ＯＳＡＳ患者（Ｏ组）及２０例单纯鼾症患者（Ｓ组）夜间睡眠前后呼吸方式及口腔阻断压（Ｐ＿（０．１））的改变，并观察了ｎＣＰＡＰ治疗对ＯＳＡＳ，患者呼吸方式及Ｐ＿（０．１）的影响。结果显示：Ｏ组患者睡前的Ｐ＿（０．１）、呼吸频率、有效吸气阻抗明显高于Ｓ组，潮气量则显著低于Ｓ组。ｎＣＰＡＰ治疗组患者经一夜睡眠后的Ｐ＿（０．１）、每分通气量、潮气量、呼吸频率等较睡前显著增高。经ｎＣＰＡＰ治疗后Ｏ组的呼吸紊乱指数较治疗前明显降低，夜间最低氧饱和度明显提高，Ｐ＿（０．１）较睡前则无明显升高。提示ＯＳＡＳ患者睡前的呼吸中枢驱动性高于单纯鼾症患者，其呼吸形式为浅快呼吸；经过一夜睡眠后，其呼吸中枢驱动水平较睡前明显增高，呼吸形式更为浅快；ｎＣＰＡＰ治疗可以有效地解除睡眠呼吸暂停及其继发的低氧血症，从而逆转睡眠前后呼吸方式和呼吸中枢驱动性的改变。     

11例睡眠呼吸暂停综合征的机械通气治疗

经鼻持续气道正压（ｎａｓａｌｃｏｎｔｉｎｏｕｓｐｏｓｉｔｉｖｅａｉｒｗａｙｐｒｅｓｓｕｒｅｎＣＰＡＰ）机械通气自１９８１年始用于治疗与睡眠呼吸暂停有关的夜间血氧饱和度下降,现愈来愈广泛地用于治疗睡眠呼吸暂停综合征（ＳＡＳ）,尤其适用于老年患者。它减弱...     

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.     

Heart Rate Variability in Obstructive Sleep Apnea: A Prospective Study and Frequency Domain Analysis

Background: Cyclic variation of the heart rate is observed during apneic spells in obstructive sleep apnea (OSA). We hypothesized that autonomic changes would affect frequency‐domain measures of heart rate variability (HRV). Methods: We studied 20 patients (15 men, 5 women, mean age 47.2 ± 12.2 years) with suspected OSA undergoing overnight polysomnography, and five patients (4 men, 1 woman, mean age 49.2 ± 8.6 years) with recently diagnosed sleep apnea undergoing polysomnography while wearing continuous positive airway pressure (CPAP). Holter monitors were applied during sleep studies and data were analyzed in 5‐minute blocks over the course of the night. Using spectral analysis, low frequency (LF) and high frequency (HF) powers were calculated for each interval. Overall mean and standard deviation (SD) for LF power, HF power, and the LF:HF ratio were recorded for each patient. Comparisons were made between patients with severe OSA (apnea hypopnea index (AHI) > 30, n = 8 ), moderate OSA (AHI 1–30, n = 5 ), without OSA (AHI < 10, n = 7 ), and patients wearing CPAP (n = 5 ). Results: Assessment of overnight LF or HF power revealed no significant difference between the four groups. The LF:HF ratio, which represents sympathovagal balance, was higher among those with moderate disease compared to normals and those with severe OSA (both P = 0.037 ). The standard deviation of the LF:HF ratio was higher among those with moderate disease compared to normals (P = 0.0064) and those with severe OSA (P = 0.0006) . OSA patients receiving CPAP behaved like patients with moderate OSA, with increased SD of the LF:HF ratio. Conclusions: The observed changes in the LF:HF ratio and its SD suggest an increased sympathetic tone and discordance in sympathovagal activity in moderate OSA, which is blunted in severe OSA. CPAP may restore autonomic defects, characteristic of severe OSA, to moderate levels.     

Blood pressure changes after automatic and fixed CPAP in obstructive sleep apnea: relationship with nocturnal sympathetic activity

Treatment of obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) usually causes a reduction in blood pressure (BP), but several factors may interfere with its effects. In addition, although a high sympathetic activity is considered a major contributor to increased BP in OSA, a relationship between changes in BP and in sympathetic nervous system activity after OSA treatment is uncertain. This study was undertaken to assess if, in OSA subjects under no pharmacologic treatment, treatment by CPAP applied at variable levels by an automatic device (APAP) may be followed by a BP reduction, and if that treatment is associated with parallel changes in BP and catecholamine excretion during the sleep hours. Nine subjects underwent 24-h ambulatory BP monitoring and nocturnal urinary catecholamine determinations before OSA treatment and 2 months following OSA treatment by APAP (Somnosmart2, Weinmann, Hamburg, Germany). Eight control subjects were treated by CPAP at a fixed level. After APAP treatment, systolic blood pressure (SBP) decreased during sleep (p < 0.05), while diastolic blood pressure (DBP) decreased both during wakefulness (p < 0.05) and sleep (p < 0.02). Similar changes were observed in subjects receiving fixed CPAP. Nocturnal DBP changes were correlated with norepinephrine (in the whole sample: r = .61, p < 0.02) and normetanephrine (r = .71, p < 0.01) changes. In OSA subjects under no pharmacologic treatment, APAP reduces BP during wakefulness and sleep, similarly to CPAP. A reduction in nocturnal sympathetic activity could contribute to the reduction in DBP during sleep following OSA treatment.     

Autonomic cardiac modulation in obstructive sleep apnea: effect of an oral jaw-positioning appliance

BACKGROUND: Patients with obstructive sleep apnea (OSA) are characterized by deranged cardiovascular variability, a well-established marker of cardiovascular risk. While long-term treatment with continuous positive airway pressure leads to a significant improvement of cardiovascular variability, little is known of the possibility of achieving the same results with other therapeutic approaches. The aim of our study was to investigate the responses of autonomic indexes of neural cardiac control to another type of OSA treatment based on an oral jaw-positioning appliance. METHODS: In 10 otherwise healthy subjects with OSA (OSA+) and in 10 subjects without OSA (OSA-) we measured heart rate, BP, and indices of autonomic cardiac regulation derived from time-domain and spectral analysis of R-R interval (RRI), before and after 3 months of treatment with the oral device. High-frequency (HF) power of RRI was taken as an index of parasympathetic cardiac modulation, and the ratio between low-frequency (LF) and HF RRI powers as an indirect marker of the balance between sympathetic and parasympathetic cardiac modulation. RESULTS: At baseline, in comparison with OSA- subjects, OSA+ subjects displayed a significantly lower RRI variance (p < 0.02) and reduced HF RRI powers (p < 0.001). After 3 months of treatment with the oral device, the OSA+ group showed a marked reduction in apnea-hypopnea index (p < 0.001), a lengthening in RRI and a significant increase in its variance (p < 0,02), an increased HF RRI power (from 134 +/- 26 to 502 +/- 48 ms2, p < 0.001), and a reduction in LF/HF RRI power ratio (from 3.11 +/- 0.8 to 1.5 +/- 0.5). As a result of these changes, after the 3-month treatment there were no more significant differences between the two groups in these parameters. In both OSA+ and OSA- groups, body weight, heart rate, and BP did not change over time. CONCLUSIONS: Three months of treatment with a specific oral jaw-positioning appliance improves cardiac autonomic modulation in otherwise healthy patients with OSA of mild degree.     

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.     

8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients. DESIGN: The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients. PATIENTS AND METHODS: Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay. Measurements and results: Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001). CONCLUSIONS: These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.     

Acute effects of autoadjusting and fixed continuous positive airway pressure treatments on cardiorespiratory coupling in obese patients with obstructive sleep apnea

BackgroundTreatment with positive airway pressure devices improved signs and symptoms of obstructive sleep apnea syndrome (OSA); however, auto-adjusting positive pressure (APAP) device was not as effective as continuous positive airway pressure (CPAP) in reducing arterial blood pressure and insulin resistance. The role played by autonomic cardiac regulation remains to be clarified.We aimed to test the effects of CPAP and APAP on autonomic regulation and cardiorespiratory coupling during sleep.MethodsWe retrospectively analyzed full-night polysomnographic studies. 19 patients newly diagnosed with severe OSA (AHI > 30) and 7 obese subjects without OSA (CON) were enrolled. Each OSA subject was assigned to CPAP or APAP treatment and underwent a sleep study after 1 week of treatment. Spectral and cross-spectral analyses of heart rate variability (HRV) and respiration were performed to assess autonomic profile and coherence (K²) between respiration and HF oscillation during sleep in CPAP, APAP and CON groups.ResultsIn CPAP and CON, LFnu and LF/HF, markers of sympathetic modulation, decreased from N2 to N3 and increased during REM sleep (p < 0.001), while in APAP group, sympathetic modulation was significantly higher compared with those of CPAP and CON during all sleep stages. K² values were lower in APAP compared with those in CPAP and CON.ConclusionAPAP treatment was characterized by a greater sympathetic activation and it was associated with a lower cardio-respiratory coupling compared with CPAP. This might account for the different effects on cardiovascular risk factors induced by the two treatments.     

Sleep apnea and heart failure

Sleep apnea is frequently observed in patients with heart failure (HF). In general, sleep apnea consists of two types: obstructive and central sleep apnea (OSA and CSA, respectively). OSA results from upper airway collapse, whereas CSA arises from reductions in central respiratory drive. In patients with OSA, blood pressure is frequently elevated as a result of sympathetic nervous system overactivation. The generation of exaggerated negative intrathoracic pressure during obstructive apneas further increases left ventricular (LV) afterload, reduces cardiac output, and may promote the progression of HF. Intermittent hypoxia and post-apneic reoxygenation cause vascular endothelial damage and possibly atherosclerosis and consequently coronary artery disease and ischemic cardiomyopathy. CSA is also characterized by apnea, hypoxia, and increased sympathetic nervous activity and, when present in HF, is associated with increased risk of death. In patients with HF, abolition of coexisting OSA by continuous positive airway pressure (CPAP) improves LV function and may contribute to the improvement of long-term outcomes. Although treatment options of CSA vary compared with OSA treatment, CPAP and other types of positive airway ventilation improve LV function and may be a promising adjunctive therapy for HF patients with CSA. Since HF remains one of the major causes of mortality in the industrialized countries, the significance of identifying and managing sleep apnea should be more emphasized to prevent the development or progression of HF.     

Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction

RATIONALE: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases. Injury of endothelial cells has been advanced as an initial trigger to atherosclerosis. OBJECTIVES: To study the association between circulating apoptotic endothelial cells and vasomotor dysfunction as a function of sleep apnea. METHODS: Brachial artery flow-mediated dilation was determined in 14 subjects with documented OSA and 10 healthy control subjects at baseline and 8 weeks after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146(+) Annexin V(+)) was performed by flow cytometry. MEASUREMENTS AND MAIN RESULTS: Compared with healthy subjects, patients with OSA had higher numbers of circulating CD146(+) Annexin V(+) cells (39.2 +/- 13.6 cells/mL and 17.8 +/- 9.4, respectively; p < 0.001). Increased apoptotic endothelial cells correlated moderately with abnormal vascular function (r = -0.61; p = 0.001). A significant correlation was observed between CD146 Annexin V(+) cells and the apnea-hypopnea index (r = 0.56; p = 0.004). After 8 weeks of treatment with CPAP, the numbers of circulating apoptotic endothelial cells were reduced significantly from 39.2 +/- 13.6 to 22.3 +/- 12.9 apoptotic cells per milliliter (p < 0.001) and correlated with improvement in endothelium-dependent vasodilation (r = 0.49; p = 0.07). CONCLUSIONS: In patients with OSA, impairment of endothelial-dependent vasodilation correlated with the degree of endothelial cell apoptosis. CPAP therapy led to significant decline in circulating apoptotic endothelial cells. These findings provide an additional mechanism for the predisposition of patients with OSA to premature vascular disease.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics.

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.