Muscle sympathetic nerve activity during wakefulness in heart failure patients with and without sleep apnea

Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction <45%. Of these, 43 had an apnea-hypopnea index > or =15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate. Daytime MSNA was significantly higher in those with sleep apnea (76+/-2 versus 63+/-4 bursts per 100 heartbeats [mean+/-SEM], P=0.005; 58+/-2 versus 50+/-3 bursts/min, P=0.037), irrespective of its etiology (the mean difference for central sleep apnea was 17 bursts per 100 heartbeats; n=14; P=0.006; and for obstructive sleep apnea, 11 bursts per 100 heartbeats; n=29; P=0.032). In a subgroup (n=8), treatment of obstructive sleep apnea lowered MSNA by 12 bursts per 100 heartbeats (P=0.003). Convergence of independent excitatory influences of HF and sleep apnea on central sympathetic neurons results in higher MSNA during wakefulness in HF patients with coexisting sleep apnea. This additional stimulus to central sympathetic outflow may accelerate the progression of HF; its attenuation by treatment of sleep apnea represents a novel nonpharmacological opportunity.     

The acute effects of continuous positive airway pressure and oxygen administration on blood pressure during obstructive sleep apnea.

We have measured blood pressure continuously with a digital artery blood pressure monitor in eight patients with severe obstructive sleep apnea (OSA) during 30 min each of wakefulness, OSA, OSA with added oxygen to keep saturation above 96 percent at all times (OSA+O2), and nasal continuous positive airway pressure (CPAP) therapy. Mean blood pressures were not different between wakefulness, OSA, OSA+O2, and CPAP, although the variability in blood pressure was significantly greater during OSA and OSA+O2 than during wakefulness and CPAP. The addition of oxygen did not attenuate the variability in blood pressure. Using multiple linear regression modeling to further dissect out the principal variables determining the postapneic blood pressure rise, we found that only apnea length (r2 = 0.28, p less than 0.0001) and pulse rate changes (r2 = 0.15, p less than 0.0001) remained significantly related to SBPmax, while hypoxemia did not. We found the same trends in the other variables SBPten, DBPmax, and DBPten. Hypoxemia made a small contribution to the size of DBPmax, although this was small by comparison with apnea length. We conclude that CPAP treatment of OSA does not lower mean blood pressure acutely, although it significantly reduces the large oscillations in blood pressure seen in patients with untreated OSA. The rise in blood pressure following each apnea is not primarily due to arterial desaturation but is related to apnea length and may be caused by increased sympathetic activity secondary to arousal.     

Sleep quality and blood pressure dipping in obstructive sleep apnea

Background:Obstructive sleep apnea (OSA) is associated with poor sleep quality and a high incidence of nondipping. The aim of this study was to determine the association of sleep quality and nocturnal blood pressure (BP) dipping in an OSA population.Methods:A total of 44 untreated subjects with mild to severe OSA underwent overnight-attended polysomnography and 24-h ambulatory BP monitoring. Subjects were off antihypertensive medication. The percentage of slow wave sleep, percentage of time awake after sleep onset during the sleep period, sleep efficiency, and arousal index were chosen as measurements of sleep quality. Dipping was evaluated using the change in systolic BP, diastolic BP, and mean arterial pressure. Patients were classified as dippers and nondippers based on a nocturnal drop in mean arterial pressure > 10%. Differences between groups were evaluated by independent sample t tests. Pearson correlation and linear regression were used to evaluate the association of sleep quality and dipping.Results:There were no differences between dippers and nondippers with regard to body mass index, age, or respiratory disturbance index. A total of 84% were nondippers. No difference was found between dippers and nondippers in sleep quality. None of the sleep quality measures correlated with the measurements of dipping. In multiple regression analyses, the percentage of slow wave sleep and arousal index each independently predicted only a small percentage of the variance (approximately 10%) of nocturnal DBP dipping.Conclusions:The prevalence of nondipping was very high in a population of untreated patients with mild to severe OSA. Nonetheless, sleep quality did not appear to be related to BP dipping.     

交感神经活性和血管内皮功能在阻塞性睡眠呼吸暂停低通气综合征合并高血压发病机制中的作用

目的探讨交感神经活性、血管内皮功能在阻塞性睡眠呼吸暂停低通气综合征（OSAHS）合并高血压发病机制中的作用。方法根据整夜多导睡眠监测（PSG）、血压测量和病史采集将93例患者分为：OSAHS血压正常组、OSAHS合并高血压组、高血压不合并OSAHS组和健康对照组。测定PSG当晚睡眠前后血压、血浆去甲肾上腺素、血浆内皮素和血清一氧化氮；收集PSG当晚22点至次晨6点的所有尿液送检尿3-甲氨基4-羟苦杏仁酸（VMA）。结果OSAHS组患者不论有无高血压，各指标变化为：晨起血浆去甲肾上腺素均显著高于睡前，OSAHS合并高血压组升高更明显；醒后去甲肾上腺素与醒后平均动脉压、睡眠呼吸暂停低通气指数（AHI）、氧减次数、氧减指数、睡眠期间血氧饱和度低于90％的时间占总睡眠时间的百分比（T90）呈显著正相关，与睡眠时最低血氧饱和度（minSaO2）和夜间平均血氧饱和度（MSaO2）呈显著负相关；醒后内皮素显著增高、一氧化氮明显下降，而另外两组则相反；醒后内皮素与醒后平均动脉压、AHI、最长呼吸暂停时间、呼吸暂停总时间、氧减次数、氧减指数、T90呈显著正相关，与minSaO2、MSaO2呈显著负相关；醒后一氧化氮与醒后平均动脉压、AHI、最长呼吸暂停时间、呼吸暂停总时间、氧减次数、氧减指数、T90呈显著负相关。与minSaO2、MSaO2呈显著正相关。各组间尿VMA无明显变化。结论在OSAHS患者夜间一过性血压升高和持续性高血压形成方面，交感神经系统活性增强、血管内皮功能紊乱导致的内皮源性舒、缩因子失衡可能起着重要的作用。     

Determinants of the Awakening Rise in Systemic Blood Pressure in Obstructive Sleep Apnea Syndrome

To investigate the factors responsible for the morning rise in blood pressure (BP) in obstructive sleep apnea syndrome (OSAS) we examined a group of 253 consecutive snorers or OSAS patients. On the basis of their AHI the patients were classified in four groups. BP was measured on the evening before sleep onset and on the following morning after 15min of rest by a finger arterial pressure device (Finapres). In 150 subjects BP was monitored during the night by a Finapres device. In the morning BP increased in the patient group with an average difference of 9.9 0.5 mmHg for systolic (SBP) and 9.9 0.4 mmHg for diastolic pressure (DBP). The increase was significant in snorers and OSAS patients without differences between groups. The morning rise in SBP was related to diurnal values of SBP, age and AHI whereas the time spent in apnea and the diurnal values of DBP significantly contributed to the DBP increase. In the subgroup of 150 patients in whom BP was analyzed during sleep, the awakening increase was related to the absolute BP value during sleep and to the BP changes from wakefulness to sleep. The magnitude of the BP changes from evening to morning was not dependent on the degree of BP variability during sleep. We conclude that the awakening increase in BP in patients with snoring or OSAS may be mediated by the setting of pressure response to apnea or to mechanical effort during sleep. Anthropometric variables and diurnal cardiovascular setting may play an additional role in modulating the final pressure response to upper airway obstruction.     

Tissue hypoxia in sleep apnea syndrome assessed by uric acid and adenosine

STUDY OBJECTIVE: Although the overnight increase in urinary uric acid/creatinine ratio (DeltaUA/Cr) is considered by some to be a marker of tissue hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), this index is not universally accepted. The purpose of this study was to confirm the validity of DeltaUA/Cr as a marker of tissue hypoxia by measuring the plasma level of adenosine during sleep, and also to test the hypothesis that the heart rate (HR) response to apnea is a determinant of tissue hypoxia. DESIGN: Intergroup comparative study. SETTING: A university hospital, Sapporo, Japan. PATIENTS: Eighteen patients with OSAS who had apnea-associated, moderate-to-severe arterial desaturation. The patients were classified into two groups: the DeltaUA/Cr-positive group, who were considered to have tissue hypoxia, and the DeltaUA/Cr-normal group, who were not. Measurements and results: Although there were no significant differences between two groups of the patients in either arterial desaturation parameters or the apnea-hypopnea index, the plasma level of adenosine during sleep was significantly higher in the DeltaUA/Cr-positive group than in the DeltaUA/Cr-normal group. Successful treatment with nasal continuous positive airway pressure significantly decreased both DeltaUA/Cr and the plasma level of adenosine only in the DeltaUA/Cr-positive group. The magnitude of the HR increase after the termination of apnea was significantly smaller in the DeltaUA/Cr-positive group. CONCLUSIONS: DeltaUA/Cr is a marker of tissue hypoxia, which does not necessarily parallel arterial desaturation indexes in OSAS. Intersubject variability in the HR response to apnea may explain the discrepancy between tissue hypoxia and arterial desaturation indexes.     

Sustained effect of continuous positive airway pressure on baroreflex sensitivity in congestive heart failure patients with obstructive sleep apnea

BACKGROUND: Patients with either heart failure or obstructive sleep apnea have a reduced baroreflex sensitivity for heart rate, a sign of poor prognosis. We previously demonstrated that nocturnal application of continuous positive airway pressure to heart failure patients with obstructive sleep apnea increased baroreflex sensitivity acutely, but it is not known whether these effects persist into wakefulness. OBJECTIVE: To determine whether treating obstructive sleep apnea in heart failure patients with continuous positive airway pressure improves baroreflex sensitivity during wakefulness. METHODS: Spontaneous baroreflex sensitivity was assessed during wakefulness in 33 heart failure patients (left ventricular ejection fraction < or = 45%) with obstructive sleep apnea (apnea-hypopnea index > or = 20). Subsequently, baroreflex sensitivity was reassessed 1 month after patients were randomly allocated to nocturnal continuous positive airway pressure treatment or no treatment (control). RESULTS: Compared with the 14 control patients, the 19 continuous positive airway pressure-treated patients experienced a greater increase in baroreflex sensitivity [median, (25%, 75%)] [from 5.4 (2.2, 8.3) to 7.9 (4.4, 9.4) ms/mmHg; P = 0.01] and left ventricular ejection fraction (P < 0.001). In addition, daytime systolic blood pressure and heart rate decreased more in the continuous positive airway pressure group (from 122 +/- 15 to 113 +/- 12 mmHg; P = 0.02, and from 66 +/- 8 to 62 +/- 8 bpm; P < 0.001, respectively) than in the control group. CONCLUSION: Treatment of coexisting obstructive sleep apnea by continuous positive airway pressure in heart failure patients improves baroreflex sensitivity during wakefulness in addition to improving left ventricular ejection fraction and lowering blood pressure and heart rate. These data indicate that the improved autonomic regulation of heart rate in heart failure patients treated for obstructive sleep apnea during sleep persists into wakefulness.     

高血压合并阻塞性睡眠呼吸暂停患者的血压变异性

目的探讨高血压合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者的血压变异性特点。方法纳入疑似OSAHS的高血压患者217例,根据睡眠呼吸暂停低通气指数(AHI)分为4组:非OSAHS组(33例),轻度OSAHS组(57例),中度OSAHS组(68例),重度OSAHS组(59例),比较各组患者血生化指标、血压及血压变异性,分析AHI与血压变异性的关系。结果 4组患者的体质量指数(BMI)和血压变异性明显不同,随睡眠呼吸暂停的严重程度增加而增大(P<0.05)。以BMI进行分层后,超重及肥胖高血压患者的夜间血压变异性随睡眠呼吸暂停严重程度的增加而增大(P<0.05)。偏相关分析显示控制年龄、BMI、血压后,AHI与24h收缩压变异性、24h舒张压变异性、白昼收缩压变异性、白昼舒张压变异性、夜间收缩压变异性及夜间舒张压变异性呈正相关(分别r=0.346,0.414,0.263,0.324,0.445,0.570,均P<0.05)。结论 AHI与血压变异性相关,睡眠呼吸暂停对夜间血压变异性影响更为明显。     

Mechanisms of pulse pressure amplification dipping pattern during sleep time: the SAFAR study

The difference in pulse pressure (PP) between peripheral arteries and the aorta, called pulse pressure amplification (PPamp), is a well-described physiological phenomenon independently associated with cardiovascular events. Recent studies suggest that it exhibits circadian variability. Our aim was to detect the factors associated with the circadian variability of PPamp. In 497 consecutive subjects (aged 54 years, 56.7% male, 79.7% hypertensives), we assessed the circadian pattern of peripheral and central arterial hemodynamics by 24-hour evaluation of brachial and aortic blood pressure (BP), augmentation index (AI), and pulse wave velocity (PWV) using a validated oscillometric device (Mobil-O-Graph). All parameters exhibited a circadian variation. Sleep dipping (decrease) pattern was observed for PPamp, brachial and aortic systolic BP, mean BP, and PWV, whereas a rising pattern (higher sleep than wake values) was observed for brachial PP, aortic PP, and AI. The factors independently associated with the less sleep dipping in PPamp were older age, lower height, the use of antihypertensive medication, and sleep decrease in arterial stiffness (PWV), whereas female gender, the presence of hypertension, sleep increase of pressure wave reflections (AI), sleep decrease in heart rate, and mean BP were associated with a greater sleep-dipping in PPamp. These data provide further pathophysiological understanding of the mechanisms leading to PPamp dipping. Several implications regarding the clinical use of the aortic and brachial BP, especially during sleep time, are raised that should be addressed in future research.     

Twenty-four-hour ambulatory BP in snoring children with obstructive sleep apnea syndrome

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a known risk factor for hypertension in adults. This relationship is less clear in childhood OSAS. OBJECTIVE: This study examined the relationship between OSAS and 24-h ambulatory BP (ABP), a more accurate assessment than casual BP, in children with snoring. METHODS: Snoring children aged 6 to 15 years who underwent polysomnography in the sleep laboratory were recruited. Measurement: Twenty-four-hour ABP monitoring was initiated a few hours before polysomnography. The children were classified into two groups: a high apnea-hypopnea index (AHI) group (obstructive AHI > 5/h), and a low-AHI group (AHI < or = 5/h). Mean sleep, wake, and 24-h systolic BP (SBP) and diastolic BP (DBP) were recorded. A child was considered a "nondipper" if his or her mean SBP and DBP did not decrease by >/= 10% during sleep. RESULTS: Ninety-six children (mean age +/- SD, 9.4 +/- 2.8 years) were recruited. Forty-one children were obese. When awake, the high-AHI group children had a significantly higher SBP. When asleep, both SBP and DBP were higher in the high-AHI group. Age, body mass index (BMI) z score, and desaturation index (DI) were significant predictors for elevated sleep DBP. BMI z score was the only significant predictor for wake and sleep SBP. Sixteen children (17%) had hypertension, and all were nondippers. Obese children in the high-AHI group had a significantly higher prevalence of hypertension than obese children in the low-AHI group. This relationship was not found in nonobese children. CONCLUSION: The current study shows that increased DI contributed to the elevation of sleep DBP elevation.     

Influence of movement arousal on circadian rhythm of blood pressure in obstructive sleep apnea syndrome

OBJECTIVE: To investigate the hypothesis that repeated arousals at the termination of apnea/hypopnea in obstructive sleep apnea syndrome (OSAS) are related to abnormal circadian rhythm of blood pressure (BP). DESIGN AND METHODS: We performed polysomnography (PSG) with pulse oximetry in 26 middle-aged patients with OSAS aged 42-58 years (mean age 51.8 years). The intensity of arousal on PSG was graded into two levels: grade 1 (EEG arousal, EA), an abrupt shift in EEG frequency, and grade 2 (movement arousal, MA), EEG arousal with an increase in electromyogram activity lasting at least 3 s. The number of apnea/hypopneas per hour (apnea/hypopnea index, AHI), and length of time during which nocturnal oxygen saturation decreased below 90% (oxygen desaturation time, ODT) were also evaluated. Percentage EA and %MA were assessed by the ratio of the number of apneas and hypopneas with EA or MA to the number of apneas and hypopneas in total. The 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively. Multiple regression analysis was performed among AHI, ODT, %EA and %MA or among age, body mass index and %MA. RESULTS: The %MA was the most significant factor contributing to the elevated 24 h SBP (r= 0.46, P< 0.05); oxygen desaturation (r= 0.44, P< 0.05) was the next most important contributing factor. The level and pattern of 24 h BP differed significantly between the patients with %MA 85% and %MA < 85% (mean 24 h SBP: 147 +/- 16.8 versus 125 +/- 19.6 mmHg, P< 0.01; mean 24 h DBP: 97.5 +/- 14.3 versus 85.6 +/- 14.6 mmHg, P< 0.01), and also differed between those with severe OSAS, i.e. ODT > or = 130 min, and mild to moderate OSAS, i.e. ODT < 130 min, (mean 24 h SBP: 149 +/- 15.8 versus 132 +/- 20.6 mmHg, P < 0.01; mean 24 h DBP: 100 +/- 14.1 versus 87.4 +/- 14.0 mmHg, P < 0.01). CONCLUSION: Our findings suggest that MA and oxygen desaturation in OSAS make an important contribution to abnormal circadian rhythm of BP. We conclude that repeated end-apneic arousal and/or hypoxic asphyxia and the subsequent sleep fragmentation may contibute to nocturnal and diurnal elevation of BP.     

24-hour BP in children with congenital central hypoventilation syndrome

OBJECTIVE: To study circadian BP patterns in patients with congenital central hypoventilation syndrome (CCHS). DESIGN: Case-control study. SETTING: Teaching hospital in Paris, France. PATIENTS: Eleven patients with CCHS (median age, 13 years; range, 6 to 18 years) and 11 sex- and height-matched control subjects. INTERVENTION: None. METHODS: Each subject underwent 24-h ambulatory BP monitoring. Oxygen saturation and end-tidal PCO(2) were monitored noninvasively. Polysomnography was performed to determine sleep times. All patients with CCHS received mechanical ventilation during sleep. Mean values for systolic BP (SBP) and diastolic BP (DBP) during wakefulness and sleep were analyzed. Nocturnal BP "dipping" was defined as the difference in mean SBP (and/or DBP) between wakefulness and sleep, divided by individual waking mean values. BP "dippers" were defined as subjects showing at least 10% nocturnal dipping. RESULTS: Patients with CCHS had BPs in the low normal range of normative data. As compared to control subjects, patients with CCHS had lower BP during wakefulness (p = 0.003 and p = 0.016 for SBP and DBP, respectively), and higher BP during sleep (p = 0.016 and p = 0.002). Nocturnal BP dipping was abnormally reduced in patients with CCHS (p = 0.000). Ten of the 11 patients with CCHS were BP nondippers, compared to none of the control subjects. CONCLUSION: The abnormal circadian BP pattern observed in children and adolescents with CCHS may be related to autonomic nervous dysfunction. Lifelong cardiovascular follow-up is recommended for patients with CCHS.     

A new technique for detecting sleep apnea-related "midnight" surge of blood pressure.

Patients with obstructive sleep apnea syndrome (OSAS) have been reported to be at greater risk for cardiovascular events, and midnight surge of blood pressure (BP) may be a mechanism of sleep apnea-related cardiovascular risk. However, there has been no accurate noninvasive technique to detect intermittent BP surge at the time of each sleep apnea episode. We therefore developed an experimental system to detect apnea-related short-term BP surge based on BP measurement triggered by peripheral (finger-tip) oxygen desaturation (a desaturation-triggered BP monitoring system). In 16 patients with OSAS, this new system successfully detected BP surges at the time of the sleep apnea, and the BP values were found to be significantly higher than those detected using a conventional fixed interval BP monitoring system (systolic BP [SBP] difference: 13 +/- 5.8 mmHg, p = 0.039; diastolic BP [DBP] difference: 10 +/- 6.8 mmHg, p = 0.032). The maximum SBP time rate (velocity of BP surge) showed a strong positive correlation with the apnea-hypopnea index (r = 0.855, p < 0.0001). In conclusion, we developed a noninvasive oxygen desaturation-triggered BP monitoring system that can successfully detect sleep apnea-related BP surge. The midnight BP surge detected by this new method was significantly associated with the severity of OSAS.     

A nasal cannula can be used to treat obstructive sleep apnea

RATIONALE: Obstructive sleep apnea syndrome is due to upper airway obstruction and is associated with increased morbidity. Although continuous positive airway pressure efficaciously treats obstructive apneas and hypopneas, treatment is impeded by low adherence rates. OBJECTIVES: To assess the efficacy on obstructive sleep apnea of a minimally intrusive method for delivering warm and humidified air through an open nasal cannula. METHODS: Eleven subjects (age, 49.7+/-5.0 yr; body mass index, 30.5+/-4.3 kg/m2), with obstructive apnea-hypopnea syndrome ranging from mild to severe (5 to 60 events/h), were administered warm and humidified air at 20 L/minute through an open nasal cannula. MEASUREMENTS AND MAIN RESULTS: Measurements were based on standard sleep-disordered breathing and arousal indices. In a subset of patients pharyngeal pressure and ventilation were assessed to determine the mechanism of action of treatment with nasal insufflation. Treatment with nasal insufflation reduced the mean apnea-hypopnea index from 28+/-5 to 10+/-3 events per hour (p<0.01), and reduced the respiratory arousal index from 18+/-2 to 8+/-2 events per hour (p<0.01). Treatment with nasal insufflation reduced the apnea-hypopnea index to fewer than 10 events per hour in 8 of 11 subjects, and to fewer than 5 events per hour in 4 subjects. The mechanism of action appears to be through an increase in end-expiratory pharyngeal pressure, which alleviated upper airway obstruction and improved ventilation. CONCLUSIONS: Our findings demonstrate clinical proof of concept that a nasal cannula for insufflating high airflows can be used to treat a diverse group of patients with obstructive sleep apnea.     

Activity-adjusted 24-hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing

Questions remain as to whether pediatric sleep disordered breathing increases the risk for elevated blood pressure and blood pressure-dependent cardiac remodeling. We tested the hypothesis that activity-adjusted morning blood pressure surge, blood pressure load, and diurnal and nocturnal blood pressure are significantly higher in children with sleep disordered breathing than in healthy controls and that these blood pressure parameters relate to left ventricular remodeling. 24-hour ambulatory blood pressure parameters were compared between groups. The associations between blood pressure and left ventricular relative wall thickness and mass were measured. 140 children met the inclusion criteria. In children with apnea hypopnea index <5 per hour, a significant difference from controls was the morning blood surge. Significant increases in blood pressure surge, blood pressure load, and in 24-hour ambulatory blood pressure were evident in those whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and body mass index had similar effect on blood pressure parameters except for nocturnal diastolic blood pressure, where sleep disordered breathing had a significantly greater effect than body mass index. Diurnal and nocturnal systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure predicted the changes in left ventricular relative wall thickness. Therefore, sleep disordered breathing in children who are otherwise healthy is independently associated with an increase in morning blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure. The association between left ventricular remodeling and 24-hour blood pressure highlights the role of sleep disordered breathing in increasing cardiovascular morbidity.     

Obstructive sleep apnea syndrome and essential hypertension: diurnal variation of urinary catecholamines]

30 subjects of old and middle age (28 male, 2 female) with obstructive sleep apnea syndrome (OSAS) and 20 normal subjects with matchable age and body weight (14 male, 6 female) as control were studied with nocturnal polysomnography for at least 7 hours. Right arm blood pressure was determined in supine position before and after sleep. Meantime, three 8-hour urine specimens, two collected while awake and one during sleep were examined for urinary levels of epinephrine (E) and norepinephrine (NE) with fluorometric method. All OSAS subjects (mean apnea index 42.9) had significant arterial oxygen desaturation (mean 63.9%). 12/30 OSAS subjects had definit history of essential hypertension. They described that hypertension appeared months or years after the onset of sleep disorders. Before sleep the blood pressure in OSAS subjects was higher than that in controls (mean 133/90 mmHg versus 118/77 mmHg P < 0.001). After 7 hours of sleep with apnea events, the blood pressure rose to 149/100 mmHg (P < 0.001). whereas in the controls there was no change of statistic significance (mean 115/77 mmHg). A diurnal rhythm in free catecholamines excretion was apparent for both NE and E (P < 0.05) in the controls, while in OSAS there was no normal diurnal rhythm. 24-hour values of NE were remarkably higher than those in controls. It is known that up to 40% of OSAS subjects is in the population of essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reproducibility of blood pressure dipping: Relation to day-to-day variability in sleep quality

Previous studies of the reproducibility of blood pressure (BP) dipping have yielded inconsistent results. Few have examined factors that may influence day-to-day differences in dipping. Ambulatory BP monitoring was performed on three occasions, approximately 1 week apart, in 115 untreated adult subjects with elevated clinic BPs. The mean ± standard deviation BP dip was 18 ± 7/15 ± 5 mm Hg (sleep/awake BP ratio = 0.87 ± 0.05/0.82 ± 0.06), with a median (interquartile range) day-to-day variation of 5.2 (3.1–8.1)/4.3 (2.8–5.6) mm Hg. There was no decrease in variability with successive measurements. The reproducibility coefficient (5.6 [95% confidence interval, 5.1–6.1] mm Hg) was greater and the intraclass correlation coefficient (0.53 [95% confidence interval, 0.42–0.63]) was smaller for the systolic dip than for 24-hour or awake systolic BPs, suggesting greater day-to-day variability in dipping. Variability in systolic dipping was greater in subjects with higher awake BP, but was not related to age, gender, race, or body mass index. Within individuals, day-to-day variations in dipping were related to variations in the fragmentation index (P < .001), a measure of sleep quality. Although mean 24-hour and awake BPs were relatively stable over repeated monitoring days, our study confirms substantial variability in BP dipping. Day-to-day differences in dipping are related to sleep quality.     

Blood pressure 24-hour rhythms and variability in adolescents with hypertension

Twenty-four hour blood pressure (BP) monitoring was used for the study of BP 24-hour rhythms and variability in adolescents with hypertension and their normotensive counterparts. The data obtained evidenced for active participation of sympatho-adrenal system in genesis of juvenile hypertension: hypertension was predominantly systolic, BP elevation as a rule was associated with increased heart rate and pulse pressure. Episodes of BP elevation were registered mostly during day time. Desynchronization of 24-hour rhythms due to pronounced BP lowering during sleep characteristic for this age group found its reflection in values of nocturnal BP dipping. More than 1/3 of adolescents with episodes of elevated BP had 'white coat' hypertension.     

Effect of triazolam on sleep and arterial oxygen saturation in patients with chronic obstructive pulmonary disease

We compared the effects of a placebo with 0.125 and 0.25 mg of triazolam (Halcion) on sleep quality, oximetry, and respiratory events during sleep in ten stable outpatients with chronic obstructive pulmonary disease. The subjects had a forced expiratory volume in 1 s ranging from 17% to 76% of the predicted value (mean +/- SD, 38.1% +/- 19%) and a waking arterial oxygen pressure from 46 to 84 mm Hg (mean +/- SD, 67 +/- 12 mm Hg). Polysomnography was done on three nights within a two-week period after the patients received on a "blinded" basis either placebo or 0.125 or 0.25 mg of triazolam. Triazolam produced improvements in total sleep duration, time spent in stage 2 nonrapid eye movement (NREM) sleep, and subjective of sleep quality. For most patients, there was a nighttime drop in arterial oxygen percentage of saturation (SaO2) in the placebo condition, but triazolam did not cause a significant worsening, of the mean SaO2, minimum SaO2, or the number of apneic and hypopneic events. Across all experimental conditions, we documented little desaturation during wakefulness (mean low, 87.2% +/- 10.2%), more during NREM sleep (mean low, 83.2% +/- 12.6%), and most desaturation in REM sleep (mean low, 80.1% +/- 15.7%). We conclude that single-night use of triazolam improved the quality and duration of sleep in patients with chronic obstructive pulmonary disease. In patients without severe waking hypoxemia and without carbon dioxide retention, triazolam did not increase either nocturnal hypoxemia or respiratory events during sleep.     

Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea

Percutaneous renal sympathetic denervation by radiofrequency energy has been reported to reduce blood pressure (BP) by the reduction of renal sympathetic efferent and afferent signaling. We evaluated the effects of this procedure on BP and sleep apnea severity in patients with resistant hypertension and sleep apnea. We studied 10 patients with refractory hypertension and sleep apnea (7 men and 3 women; median age: 49.5 years) who underwent renal denervation and completed 3-month and 6-month follow-up evaluations, including polysomnography and selected blood chemistries, and BP measurements. Antihypertensive regimens were not changed during the 6 months of follow-up. Three and 6 months after the denervation, decreases in office systolic and diastolic BPs were observed (median: -34/-13 mm Hg for systolic and diastolic BPs at 6 months; both P<0.01). Significant decreases were also observed in plasma glucose concentration 2 hours after glucose administration (median: 7.0 versus 6.4 mmol/L; P=0.05) and in hemoglobin A1C level (median: 6.1% versus 5.6%; P<0.05) at 6 months, as well as a decrease in apnea-hypopnea index at 6 months after renal denervation (median: 16.3 versus 4.5 events per hour; P=0.059). In conclusion, catheter-based renal sympathetic denervation lowered BP in patients with refractory hypertension and obstructive sleep apnea, which was accompanied by improvement of sleep apnea severity. Interestingly, there are also accompanying improvements in glucose tolerance. Renal sympathetic denervation may conceivably be a potentially useful option for patients with comorbid refractory hypertension, glucose intolerance, and obstructive sleep apnea, although further studies are needed to confirm these proof-of-concept data.