Clinical significance of ventricular late potentials in patients with obstructive sleep apnoea

SUMMARY  Patients with obstructive sleep apnoea (OSA) have an increased cardiovascular mortality and probably also an increased incidence of sudden cardiac death. Thus the question arises whether ventricular late potentials can constitute markers for an increased electric vulnerability in these patients. Signal-averaged electrocardiograms were recorded in 64 patients (6 female, 58 male; mean age 53.2 y) with OSA (mean apnoea-hypopnoea index (AHI) 41.7 h^-1 ± 24.3 h^-1). Furthermore, a continuous ambulatory electrocardiogram and gated radionuclide ventriculography were performed. Ventricular late potentials were recorded in 5 men out of 64 patients. Two of them had coronary artery disease (1 patient post-myocardial infarction), 2 hypertension, and 1 nocturnal hypertension. No correlation could be traced between left ventricular ejection fraction, severity and extent of ventricular premature beats, or severity of OSA and occurrence of ventricular late potentials. It was noticeable, however, that the patients with ventricular late potentials had severe OSA (mean AHI 50.2/h vs. 40.9/h). Although OSA may lead to structural myocardial changes that could be the basis for re-entrant circuits, ventricular late potentials were found in only 7.8% of these patients. The results of this study demonstrate that at present ventricular late potentials and signal-averaged electrocardiograms do not prove useful as screening methods for risk stratification of patients with OSA.     

Congestive heart failure and sleep apnoea—possible mechanisms and effect of CPAP therapy

SUMMARY  Sleep-disordered breathing has been associated with increased cardiovascular morbidity and mortality. However, despite several plausible mechanisms whereby obstructive sleep apnoea might be associated with left ventricular dysfunction and congestive heart failure, only limited data exist linking those disorders. These studies are reviewed along with possible mechanisms leading to left ventricular dysfunction in obstructive sleep apnoea. Recent investigations demonstrating improvement in left ventricular function after CPAP therapy in patients with congestive heart failure are reviewed as well. Finally, new data are presented from an animal model of congestive heart failure demonstrating a beneficial effect of CPAP on cardiac index in association with a decline in systematic vascular resistance. Remarkably, these effects persisted even after CPAP was removed. Possible mechanisms whereby CPAP may lead to improvement in cardiac output are discussed.     

Cortico-motoneurone excitability in patients with obstructive sleep apnoea

A disordered neuromotor control of pharynx muscles may play a role in the genesis of obstructive sleep apnoea syndrome (OSAS). This raises the possibility of a dysfunction of projections descending from the cortex to segmental nuclei. With single pulse transcranial magnetic stimulation (TMS) we studied the physiology of the corticospinal projection to hand muscles in seven OSAS patients. At first, we compared them with nine age- and sex-matched normal controls in the wake state. The only abnormality was a lengthening of the central silent period (P < 0.001). This supports a steady imbalance of motor cortical interneurone activities towards a state of enhanced inhibition. Then we looked at changes of the motor-evoked potential (MEP) size and latency, according to whether patients were awake, or in a non-rapid eye movement (REM) 2 sleep stage, or during a typical apnoea. During non-REM 2 sleep, the average MEP amplitude was significantly (P < 0.05) smaller than in the awake state. The MEP latency was, in turn, significantly longer (P < 0.05). During apnoeas, the MEP size decreased, and the latency increased further (P < 0.05), indicating an extra depression of the cortico-motoneuronal activity. All TMS changes were detected outside the pharyngeal district, suggesting a widespread dysfunction of the cortico-motoneuronal system in the OSAS, which is more evident during apnoeas.     

Arousal in obstructive sleep apnoea patients is associated with ECG RR and QT interval shortening and PR interval lengthening

Sudden cardiac death appears to be more prevalent during the normal sleeping hours in obstructive sleep apnoea (OSA) patients compared with the general population as well as to cardiovascular disease patients. The reasons for this remain unclear, but there are three likely main contributors to nocturnal death in OSA patients; cardiac arrhythmias, stroke/ruptured cerebral aneurism and myocardial infarction. Particularly marked cardiovascular system activation with arousal may play a role in initiating sudden adverse cardiovascular events in OSA. The purpose of this study was to investigate cardiac RR, QT and PR interval changes in the electrocardiogram (ECG) associated with spontaneous and respiratory-related arousals in OSA patients. A detailed observational study of ECG records obtained during conventional diagnostic sleep study with no further interventions was carried out in 20 patients (12 males, age 42.8 ± 2.1 years, body mass index 35.1 ± 1.9 kg m⁻², and respiratory disturbance index 51.8 ± 6.4 events/hour). RR and QT intervals showed significant shortening during arousals. RR interval shortening was found to be greater during respiratory arousals when compared to spontaneous arousals. PR interval showed a trend toward a greater prolongation during respiratory arousal. QT interval shortening was weakly correlated with arterial oxygen saturation levels preceding arousal. In conclusion, these data suggest that despite greater cardiac acceleration following respiratory versus spontaneous arousals from sleep, QT shortening and PR prolongation responses are similar independent of arousal type. These data support that arousals produce quite marked and differential cardiac conduction system activation in OSA and that the degree and pattern of activation may be partly influenced by the presence and severity of preceding respiratory events.     

Effect of upper airway surgery on heart rate variability in patients with obstructive sleep apnoea syndrome

To determine whether surgery influences cardiovascular autonomic modulation in obstructive sleep apnoea syndrome (OSAS), the present study was performed to evaluate the effect of upper airway (UA) surgery on heart rate variability (HRV) using frequency domain analysis for patient groups who have had either successful or unsuccessful surgery. We compared body mass index (BMI), polysomnographic [apnoea index (AI), apnoea-hypopnoea index (AHI), minimum SaO(2)] and HRV [very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power, HF/LF ratio, LFnu = LF/(LF + HF), HFnu = HF/(LF + HF)] parameters between the unsuccessful (n = 14) and successful (n = 22) surgical groups before and after UA surgery. Significant changes were observed for the successful patient group with respect to mean AI (from 29.1 ± 21.3 to 2.0 ± 3.2 events h(-1), P < 0.001), AHI (from 38.6 ± 20.0 to 5.6 ± 5.1 events h(-1), P < 0.001), minimum SaO(2) (from 73.3 ± 12.7 to 86.3 ± 6.5%, P < 0.001), VLF power (from 25599 ± 12906 to 20014 ± 9839 ms(2), P = 0.013), LF power (from 17293 ± 7278 to 14155 ± 4980 ms(2), P = 0.016), LFnu (from 0.700 ± 0.104 to 0.646 ± 0.128, P = 0.031) and HFnu (from 0.300 ± 0.104 to 0.354 ± 0.128, P = 0.031); however, mean BMI, HF power and LF/HF ratio did not change significantly after UA surgery. No significant changes were observed in the unsuccessful surgical group. Successful UA surgery may improve cardiac sympathetic and parasympathetic modulation in patients with OSAS.     

Autonomic markers of arousal during sleep in patients undergoing investigation for obstructive sleep apnoea, their relationship to EEG arousals, respiratory events and subjective sleepiness

Estimating the degree of sleep fragmentation is an important part of a respiratory sleep study and is conventionally measured using EEG micro arousals or is inferred indirectly from respiratory abnormalities such as apnoeas and desaturations. There is a need for less labour-intensive measures of sleep fragmentation, and transient rises in blood pressure and heart rate may fulfil this role. Forty unselected sleep clinic referrals undergoing investigation for possible obstructive sleep apnoea (OSA) were studied with one night of polysomnography. Three conventional indices of sleep fragmentation (EEG micro arousals, apnoea/hypopnoea index (AHI) and oxygen saturation dip rate (SaO₂ dips)) and two autonomic indices (heart rate and blood pressure rises) have been compared. Correlations between these five indices ranged from r=0.38 to r=0.73. Of the two autonomic indices, the correlations for blood pressure rises with SaO₂ dips and EEG micro arousals were stronger (r=0.71 and r=0.65, respectively) than those for heart rate rises (0.55 and 0.51). All indices of sleep fragmentation, apart from heart rate rises, were similar in their correlation with subjective sleepiness (r-values 0.21–0.36). Arousals implied from blood pressure rises (using pulse transit time) can be measured easily, are objective, and appear no worse at predicting subjective sleepiness than either EEG micro arousals or AHI. They may therefore provide a useful alternative to manual scoring of micro arousals from the EEG as an index of sleep fragmentation in sleep clinic patients undergoing investigation for possible OSA.     

Executive functions and cognitive subprocesses in patients with obstructive sleep apnoea

In recent years, special interest has been focused on impairments of executive functions in patients with obstructive sleep apnoea syndrome (OSAS). However, the majority of studies have not clearly separated deficits in executive functions from impairments in other cognitive processes involved in task solving. In the present study, working memory (WM) functions of 20 patients with OSAS were compared with those of 10 age-, sex- and education-matched healthy subjects. Cognitive functions were measured four times a day; each of these measurements was accompanied by an assessment of subjective and objective daytime sleepiness. To separate dysfunctions of WM from those of additionally involved processes, n -back tasks were applied embedded in a reaction-time-decomposition approach. Deficits in n -back tasks could be observed in OSAS patients in accuracy and reaction times. However, the slowing could already be observed in simple reaction time tasks. The drop in 1-back accuracy in the morning was related to daytime sleepiness. During the afternoon, accuracy of OSAS patients dropped in 2-back tasks, an effect which correlated neither with sleepiness nor with the extent of sleep apnoea or oxygen desaturation. In conclusion, our data reflect a complex perspective upon cognitive deficits in OSAS. Cross-group differences in processing time on the higher level WM task appeared to be attributable to slowing at a more elementary cognitive processing level. In contrast, reduced accuracy during the WM task in the OSAS group could not be explained by deficits in more elementary cognitive processes.     

定量组织速度成像对阻塞性睡眠呼吸暂停综合征患者腭咽成形术前左心功能的研究

目的应用定量组织速度成像(QTVI)技术,对拟行改良腭咽成形术的阻塞性睡眠呼吸暂停综合征(OSAS)患者左心室功能的早期变化进行研究。方法 A组,35例OSAS患者,均为男性,年龄21～58岁,平均年龄41.27岁。B组33例,健康者,均为男性,年龄22～55岁,平均年龄39.57岁。B组年龄、性别、体质量指数与A组相匹配,为对照组。用常规超声心动图和QTVI新技术,对其心脏形态结构和功能进行各节段参数测定。结果 A组与B组间常规超声参数比较:主动脉根部内径(AOD)、左心室舒张末期内径(LVDd)、左心室后壁厚度(LVPWT)和二尖瓣前向血流速度舒张早期与舒张晚期的比值(E/A)差异有统计学意义(P<0.05);二尖瓣环部分节段QTVI技术参数中舒张早期峰值速度(Ve)部分节段减低、舒张晚期峰值速度(Va)部分节段增高、Ve/Va比值部分节段减低,与B组比较差异有统计学意义(P<0.05),收缩期峰值速度(Vs)二组间差异无统计学意义(P>0.05)。结论 QTVI检测的二尖瓣环运动速度在判断左心室收缩和舒张功能早期变化方面有重要价值,能早期发现OSAS患者部分指标已有增加趋势,为临床手术前、后监测左心功能变化提供参考数据。     

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea–hypopnoea index (AHI) 5–15 h^?1] and 40 controls (AHI <5 h^?1). Serum concentrations of pro‐ and anti‐inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non‐steroidal anti‐inflammatory medication, the mean level of tumour necrosis factor‐α was significantly elevated (1.54 versus 1.17 pg mL^?1, P = 0.004), whereas the level of interleukin‐1β (IL‐1β) was reduced (0.19 versus 0.23 pg mL^?1, P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti‐inflammatory cytokines, interleukin‐10 (1.28 versus 0.70 pg mL^?1, P < 0.001) and interleukin‐1 receptor antagonist (478 versus 330 pg mL^?1, P = 0.003) were elevated in the OSA group. The concentrations of C‐reactive protein increased, but IL‐1β decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro‐inflammatory, but also with the anti‐inflammatory systems.     

Increase in serum haptoglobin and apolipoprotein M in patients with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a common syndrome, which is associated with a number of medical problems that impact morbidity and mortality. Although the precise mechanisms that underlie these associations are not fully understood, previous studies have suggested that patients with OSA show elevations of several biomarkers that are associated with cardiovascular risk. This study was undertaken to identify serum proteins associated with OSA by using a proteomics technique and to examine changes in identified protein levels after continuous positive airway pressure treatment. The study participants consisted of 40 male patients (aged 40–49 years) with severe OSA and 34 male control subjects matched for age and body mass index. All subjects underwent polysomnography. Using a proteomics approach, we identified nine proteins that were differentially expressed in patients with severe OSA and controls. Three of these nine proteins, haptoglobin, paraoxonase-1 and apolipoprotein M, were quantified by using enzyme-linked immunosorbent assays, kinetic assays and by using Western blotting. Multiple regression analysis showed that haptoglobin and apolipoprotein M levels are independently related to apnoea–hypopnoea index ( P  < 0.01). A further study is required to determine the nature of associations between these identified proteins and OSA in a large population.     

Diagnosis of sleep-disordered breathing in patients with chronic heart failure: evaluation of a portable limited sleep study system

Sleep-disordered breathing (SDB) is common in chronic heart failure (CHF), affects disease progression and presents a potential therapeutic target. This study was designed to test the hypothesis that there would be good agreement in diagnostic outcome between home limited sleep studies and in-laboratory polysomnography (PSG) in the identification of SDB in patients with CHF. We performed synchronous in-laboratory Embletta and PSG, and home Embletta studies, prospectively in 20 consecutive patients with stable symptomatic CHF (ejection fraction 33 +/- 12%) on optimal medical therapy. Sleep efficiency was poor at 57 +/- 21%. Unlike synchronous in-laboratory Embletta (kappa coefficient 0.63, P < 0.01), home Embletta showed poor agreement with PSG (kappa coefficient 0.27, P = 0.06). Positive and negative predictive values for home Embletta in detecting SDB were 83% and 57% respectively. In this relatively small study, agreement in diagnostic outcome between home Embletta and PSG, and negative predictive value for the home Embletta, were poor. We explore possible explanations for this, both technical and situational, which should be taken into consideration when considering potential screening or diagnostic tools for SDB in patients with CHF.     

Nasal pillows as an alternative interface in patients with obstructive sleep apnoea syndrome initiating continuous positive airway pressure therapy

Side‐effects directly due to the nasal mask are common in patients with obstructive sleep apnoea syndrome (OSAS) commencing continuous positive airway pressure (CPAP). Recently, nasal pillows have been designed to overcome these issues. Limited evidence exists of the benefits and effectiveness of these devices. Twenty‐one patients (19 male, 49 ± 10 years) with the established diagnosis of OSAS [apnoea/hypopnoea index (AHI): 52 ± 22] and who had a successful CPAP titration were commenced on CPAP therapy (10 ± 2 cmH2O), and randomized to 4 weeks of a nasal pillow (P) and a standard nasal mask (M) in a crossover design. Outcome measures were objective compliance, AHI, quality of life, Epworth Sleepiness Score (ESS) and CPAP side‐effects. There was no difference in compliance (M versus P: 5.1 ± 1.9 h versus 5.0 ± 1.7 h; P = 0.701) and AHI (2.6 ± 2.7 versus 3.0 ± 2.9; P = 0.509). Quality of life and ESS improved with CPAP, but there was no difference in the extent of improvement between both devices. Usage of nasal pillows resulted in less reported pressure on the face and more subjects found the nasal pillow the more comfortable device. However, there was no clear overall preference for either device at the end of the study (mask = 57%, pillow = 43%; P = 0.513). The applied CPAP pressure did not correlate with compliance, AHI and ESS. Furthermore, no differences in outcome parameters were noted comparing groups with CPAP pressure <10 and ≥10 cm H₂O. Nasal pillows are equally effective in CPAP therapy, but do not generally lead to improved compliance.     

Excessive daytime sleepiness in patients suffering from different levels of obstructive sleep apnoea syndrome

Excessive daytime sleepiness (EDS) is a frequent symptom of patients with obstructive sleep apnoea (OSA). EDS is a high-risk factor for accidents at work and on the road. Thirty untreated patients with different levels of severity of OSA were studied concerning night sleep and EDS. The criterion for severity was the respiratory disturbance index (RDI): 15 patients were classified as 'moderately' apnoeic (RDI < 40), 15 as 'severely' apnoeic (RDI > 40). Following night-time polysomnography, objective and subjective aspects of EDS were studied. To assess objective EDS the Maintenance of Wakefulness Test (MWT) and a computer-based vigilance performance test were used. Subjective EDS was determined using the Stanford Sleepiness Scale (SSS), the Epworth Sleepiness Scale (ESS) and the Visual Analogue Scales for Performance (VAS-P) and Tiredness (VAS-T). Well-being was assessed using the Scale of Well-Being by von Zerssen (Bf-S/Bf-S'). Severe apnoea patients spent more time in stage 1 and less in slow-wave sleep. MWT latencies tended to be shorter in the severe apnoea group. Vigilance testing revealed no group differences. Patients with moderate apnoea described themselves as more impaired in all subjective scales, but only SSS scores reached statistical significance. Our results suggest that there is no simple correlation between polysomnographic and respiratory sleep variables at night on the one hand, and the extent of EDS on the other hand. Furthermore, subjective and objective evaluation of EDS does not yield the same results. New approaches which allow a more detailed analysis of night sleep and daytime function are required to identify high-risked patients.     

The nocturnal secretion of cardiac natriuretic peptides during obstructive sleep apnoea and its response to therapy with nasal continuous positive airway pressure

The nocturnal secretion profile of the newly identified natriuretic peptide (NP), brain natriuretic peptide (BNP), was studied in 14 patients with obstructive sleep apnoea syndrome (OSAS) (apnoea hypopnoea index: 60.5±3.4, mean±SE) during two separate nights before and during nasal continuous positive airway pressure (NCPAP) therapy. Plasma levels of NPs (atrial natriuretic peptides; ANP and BNP) were measured at 2-h intervals during sleep. Simultaneously, blood pressure was measured by a non-invasive method (Finapres^®, Ohmeda, Englewood, CO, USA) and urine was collected for determing volume and catecholamine levels. Urinary and serum sodium concentration were determined before and after the study. Eight non-snoring subjects were also studied for the investigation of normal nocturnal profiles of BNP levels. To understand the discrete secretion profiles of the two NPs during sleep, blood was sampled from an additional seven patients every 5 min over a 30-min period around 00.00 and 04.00 hours before NCPAP. In patients with OSAS, plasma BNP levels increased from the beginning of sleep (22:00 h) to the morning (06:00 h) before NCPAP therapy (P< 0.01, anova ). Baseline BNP levels were not significantly correlated with patient's clinical and poly- somnographic parameters. However, in the latter half of the sleep period (02:00–06:00 h), increases in BNP levels during the night before NCPAP therapy were significantly correlated with blood pressure elevations (systolic: r=0.784 P< 0.01, diastolic: r=0.587 P< 0.01) and with apnoea duration (r=0.582 P< 0.01). In normal subjects BP and BNP levels were not changed significantly during sleep. Plasma BNP levels were well correlated with concomitant ANP levels (P< 0.001). NCPAP therapy reduced ANP and BNP levels during sleep and in the morning (P< 0.01). Plasma levels of BNP at 5 min intervals before NCPAP therapy revealed few variations. On the other hand, ANP levels fluctuated over the 30-min period. Changes in BNP levels during sleep in the patients with OSAS may be related to blood pressure variations, but may be too small to play a significant physiological role in regulating diuresis in OSAS. Further work is required to determine the precise role of dual natriuretic system in cardiovascular load and natriuresis in OSAS.     

阻塞性睡眠呼吸暂停综合征患者轻度认知功能障碍的MoCA评估

目的 探讨简易精神状态检查量表(MMSE)、蒙特列尔认知评估量表(MoCA)评估阻塞性睡眠呼吸暂停综合征(OSAS)患者轻度认知功能障碍(MCI)的可行性.方法 用便携式多导睡眠仪、MMSE及MoCA对51名OSAS患者和35名单纯鼾症者进行睡眠监测和认知功能的评价.结果 OSAS组MoCA评分结果为21.1 ±3.0,显著低于对照组的25.0 ±2.6(P＜0.01);MMSE评分结果在OSAS组与对照组中分别为27.8±1.8及28.1±1.7,无统计学意义.结论 MoCA对于OSAS患者MCI的早期诊断敏感性优于MMSE,对于MMSE测试结果正常但高度怀疑存在MCI者,MoCA是一种简便可行的筛查工具.     

Evaluation of pharyngeal shape and size using anatomical optical coherence tomography in individuals with and without obstructive sleep apnoea

This study compared shape, size and length of the pharyngeal airway in individuals with and without obstructive sleep apnoea (OSA) using a novel endoscopic imaging technique, anatomical optical coherence tomography (aOCT). The study population comprised a preliminary study group of 20 OSA patients and a subsequent controlled study group of 10 OSA patients and 10 body mass index (BMI)-, gender- and age-matched control subjects without OSA. All subjects were scanned using aOCT while awake, supine and breathing quietly. Measurements of airway cross-sectional area (CSA) and anteroposterior (A-P) and lateral diameters were obtained from the hypo-, oro- and velopharyngeal regions. A-P : lateral diameter ratios were calculated to provide an index of regional airway shape. In all subjects, pharyngeal CSA was lowest in the velopharynx. Patients with OSA had a smaller velopharyngeal CSA than controls (maximum CSA 91 +/- 40 versus 153 +/- 84 mm(2); P < 0.05) but comparable oro- (318 +/- 80 versus 279 +/- 129 mm(2); P = 0.48) and hypopharyngeal CSA (250 +/- 105 versus 303 +/- 112 mm(2); P = 0.36). In each pharyngeal region, the long axis of the airway was oriented in the lateral diameter. Airway shape was not different between the groups. Pharyngeal airway length was similar in both groups, although the OSA group had longer uvulae than the control group (16.8 +/- 6.2 versus 11.2 +/- 5.2 mm; P < 0.05). This study has shown that individuals with OSA have a smaller velopharyngeal CSA than BMI-, gender- and age-matched control volunteers, but comparable shape: a laterally oriented ellipse. These findings suggest that it is an abnormality in size rather than shape that is the more important anatomical predictor of OSA.     

Impairment of daytime cerebrovascular reactivity in patients with obstructive sleep apnoea syndrome

Several studies have demonstrated a clear association between snoring, sleep apnoea and increased risk of stroke. However, the possible role of sleep apnoea in the pathophysiogenetic mechanisms of cerebrovascular disease is still unknown. Our aim in this study was to investigate cerebral haemodynamic changes during the waking state in eight patients with sleep apnoea syndrome (OSAS) by means of transcranial Doppler (TCD). In particular, we studied cerebral vascular reactivity (CVR) to hypercapnia calculated by means of the breath holding index (BHI). The investigation was performed in the early morning, soon after awakening, and in the late afternoon. Data were compared with those of eight healthy subjects matched for age and vascular risk factors. OSAS patients showed significantly lower BHI values with respect to controls both in the morning (0.56 vs. 1.36; P < 0.0001) and in the afternoon (1.12 vs. 1.53; P < 0.0001). In patients, BHI values in the afternoon were significantly higher than in the morning ( P < 0.0001). These data demonstrate a diminished vasodilator reserve in OSAS patients, particularly evident in the morning. This reduction of the possibility of cerebral vessels to adapt functionally in response to stimulation could be linked to hyposensitivity of cerebrovascular chemoreceptors after the continuous stress caused by nocturnal hypercapnia.