Therapy with noninvasive ventilation in patients with obstructive sleep apnoea: Effects on atherogenic lipoprotein phenotype

Patients with obstructive sleep apnoea are at increased risk of atherosclerotic morbidity and mortality. Abnormalities in lipid metabolism that occur in response to chronic intermittent hypoxia in patients with sleep-disordered breathing may increase the cardiovascular risk in an already susceptible population. Atherogenic lipoprotein phenotype and small, dense LDL have an independent predictive role for future cardio- and cerebro-vascular events in patients with the metabolic syndrome. Therefore, testing the hypothesis that therapy of obstructive sleep apnoea may reduce atherogenic lipoprotein phenotype might have significant clinical implications. We suggest that abolition of obstructive sleep apnoea by continuous positive airway pressure results in reductions in circulatory levels of small, dense LDL by improvements in oxygen saturation, reductions in oxidative stress, improvements in insulin sensitivity, and reductions in triglyceride biosynthesis. Testing the proposed hypothesis may contribute to improvements in clinical management of patients with obstructive sleep apnoea by early recognition of atherogenic dyslipidaemia followed by both, vigorous treatment of the underlying sleep-disordered breathing by noninvasive ventilation and targeted therapeutic modulation of hypertriglyceridaemia, low HDL-cholesterol and increased levels of small, dense LDL. Implementing this strategy to patients with obstructive sleep apnoea may potentially contribute to substantial reduction of their high cardiovascular risk.     

Sympathetic nerve activity in obstructive sleep apnoea

The mechanisms underlying the link between obstructive sleep apnoea (OSA) and cardiovascular disease are not completely established. However, there is increasing evidence that autonomic mechanisms are implicated. A number of studies have consistently shown that patients with OSA have high levels of sympathetic nerve traffic. During sleep, repetitive episodes of hypoxia, hypercapnia and obstructive apnoea act through chemoreceptor reflexes and other mechanisms to increase sympathetic drive. Remarkably, the high sympathetic drive is present even during daytime wakefulness when subjects are breathing normally and no evidence of hypoxia or chemoreflex activation is apparent. Several neural and humoral mechanisms may contribute to maintenance of higher sympathetic activity and blood pressure. These mechanisms include chemoreflex and baroreflex dysfunction, altered cardiovascular variability, vasoconstrictor effects of nocturnal endothelin release and endothelial dysfunction. Long-term continuous positive airway pressure treatment decreases muscle sympathetic nerve activity in OSA patients. The vast majority of OSA patients remain undiagnosed. Unrecognized OSA may contribute, in part, to the metabolic and cardiovascular derangements that are thought to be linked to obesity, and to the association between obesity and cardiovascular risk. Furthermore, acting through sympathetic neural mechanisms, OSA may contribute to or augment elevated levels of blood pressure in a large proportion of the hypertensive patient population.     

Obesitas-Hypoventilations-Syndrom

The prevalence of extreme overweight is showing a markedly increasing tendency and obesity hypoventilation syndrome (OHS) is one of the major diseases associated with obesity. Obesity is defined as a body mass index >?30?kg/m² and daytime hypercapnia and is generally accompanied by sleep-related breathing disorders, such as obstructive sleep apnea syndrome or hypoventilation during sleep. Morbidity and mortality are significantly increased in the patients affected while the symptoms remain unspecific. A systematic search for hypercapnic events during wakefulness is essential in patients at risk. The pathophysiology includes a reduction of lung function and the ventilatory drive and sleep-related breathing disorders. In addition to dietary, surgical or drug therapies for obesity, continuous positive airway pressure (CPAP) or non-invasive ventilation are applied to improve the clinical symptoms and prognosis of these patients.     

Leistungsf?higkeit �C atmen, arbeiten, schlafen

Sleep-disordered breathing leads to sleep fragmentation with increased excessive daytime sleepiness (EDS) and reduced daytime performance. A restorative night sleep with normal pulmonary gas exchange contributes particularly to increase overall performance. Short repetitive hypoxia, for example, as part of apneas and hypopneas in obstructive sleep apnea (OSA) can induce damage to brain cells. Hippocampal neurons which have an important function in synaptic plasticity and memory formation respond very sensitively to intermittent hypoxia. With positive pressure breathing, e.g., continuous positive airway pressure (CPAP), both the hypoxia and the associated arousals can be prevented, and an improvement in neurocognitive function be achieved. In the modern world of work, a high degree of alertness in addition to physical fitness is required. The effects of disturbed sleep on professional capacity are considerable. Daytime sleepiness as the main symptom of sleep-related breathing disorders increases the risk of work accidents. Even with shift work, the risk of accidents due to sleepiness/drowsiness/fatigue with sleep attacks is increased. During rehabilitation, sleep disorders and sleep-related breathing disorders should be considered due to the high prevalence. By treating these diseases, rehabilitative measures result in particularly large effects on physical and mental performance.     

Daytime sleepiness and neural cardiac modulation in sleep-related breathing disorders

Sleep-related breathing disorders are common causes of excessive daytime sleepiness, a socially and clinically relevant problem. Mechanisms responsible for daytime sleepiness are still largely unknown. We investigated whether specific alterations in autonomic cardiac modulation during sleep, commonly associated with sleep-related breathing disorders, are related to excessive daytime sleepiness. Fifty-three patients with sleep-related breathing disorders underwent nocturnal polysomnography. Excessive daytime sleepiness was diagnosed as a Multiple Sleep Latency Test response less than or equal to 600 s. We explored the relation of excessive daytime sleepiness, objectively determined, with indices of autonomic cardiac regulation, such as baroreflex sensitivity and heart rate variability, with polysomnographic indices of the severity of sleep-related breathing disorders and with quality of sleep. Patients with excessive daytime sleepiness, when compared with patients without, had significantly lower baroreflex sensitivity and significantly higher low-to-high frequency power ratio of heart rate variability during the different stages of nocturnal sleep. By contrast, no differences were found in indices quantifying the severity of sleep-related breathing disorders or sleep quality. We demonstrated that excessive daytime sleepiness is accompanied by a deranged cardiac autonomic control at night, the latter probably reflecting autonomic arousals not detectable in the EEG. As abnormal autonomic regulation is also known to be associated with increased cardiovascular risk, a possible relation between excessive daytime sleepiness and cardiovascular events in patients with sleep-related breathing disorders deserves to be investigated in future studies.     

Sleep-disordered breathing and cardio- and cerebrovascular diseases: 2003 update of clinical significance and future perspectives

Summary The purpose of this review is to summarize current knowledge about the link between sleep-disordered breathing (SDB) and cardiovascular and cerebrovascular diseases. Obstructive sleep apnoea (OSA) is a well-established risk factor for systemic arterial hypertension, and its treatment with continuous positive airway pressure leads to a decrease in daytime and night-time blood pressure profiles. Pulmonary arterial hypertension occurs in 20–30% of OSA patients and is usually mild. It is not yet clear if OSA per se leads to pulmonary hypertension or if the coexistence of chronic obstructive pulmonary disease with daytime and/or sleep-related hypoxaemia is required to provoke a persistent rise in pulmonary artery pressure. Furthermore, OSA is associated with nocturnal cardiac arrhythmias, especially cyclical fluctuations of the heart rate in response to recurrent apnoeas. Atrioventricular conduction blocks and ventricular premature beats are less often observed and seem to be confined to patients with severe OSA and those with accompanying ischaemic heart disease. The association between OSA and vaso-occlusive disease (i.e. atherosclerosis) is less clear. However, accumulating experimental and epidemiological data support such a link. Thus, OSA may lead to coronary artery disease (CAD) and stroke by promoting atherosclerosis. Correspondingly, patients with CAD or acute stroke show a high prevalence of SDB. Cheyne–Stokes respiration (CSR) is a specific pattern of central sleep apnoea occurring in patients with advanced congestive heart failure (CHF). If present, CSR clearly has a negative impact on the clinical course of CHF. Although the optimal treatment strategy for CSR is less well defined than that for OSA, the successful reversal of CSR might increase overall survival in affected patients.     

MESAM: a heart rate and snoring recorder for detection of obstructive sleep apnea

The high prevalence of sleep-related breathing disorders demands the development of ambulatory recording devices that can handle data with a high degree of selectivity and are easy to use and to interpret. A digital device based on the recording of heart rate and breathing sounds was developed. Patients with sleep-related breathing disorders can be preselected before they undergo sleep laboratory investigations. Treatment control can be achieved ambulatory, having an initial recording.     

Screening for sleep‐disordered breathing with Pediatric Sleep Questionnaire in children with underlying conditions

The Pediatric Sleep Questionnaire described by Chervin et al. (Sleep Medicine, 2000, 1, 21–32) was originally validated for children with obstructive sleep apnoea syndrome but without other disorders. The aim of our study was to check the applicability of this questionnaire in children with underlying chronic medical conditions. Children aged 2–18 years who underwent a diagnostic sleep study at Great Ormond Street Hospital were recruited over a 10‐month period. The Pediatric Sleep Questionnaire completed by their parents and cardiorespiratory polygraphy were scored. Sensitivities and specificities of the Pediatric Sleep Questionnaire were calculated using a Pediatric Sleep Questionnaire score of 0.33 as being indicative of sleep‐disordered breathing. A total of 561 patients were reviewed. Neuromuscular disorders (n = 108), craniofacial anomalies (n = 58) and the obstructive sleep apnea syndrome control group (n = 155) were best represented. The sensitivity for patients with isolated obstructive sleep apnoea syndrome was 76.5% when using an apnoea–hypopnoea index ≥ 5, but this was much lower when looking at specific sub‐groups such as neuromuscular patients (25%) or patients with Trisomy 21 (36.7%). Sensitivities remained unchanged for patients with obstructive sleep apnoea syndrome (77.3%) when an apnoea–hypopnoea index of ≥ 1 was used, but improved for neuromuscular disorders sub‐groups (36.7%) and Trisomy 21 (84%). In conclusion, the Pediatric Sleep Questionnaire is not a good screening tool for obstructive sleep apnoea syndrome in children with complex underlying disorders when a cut‐off apnoea–hypopnoea index of ≥ 5 is used, and it cannot replace cardiorespiratory polygraphy recording.     

Cure of sleep apnea syndrome after long-term nasal continuous positive airway pressure therapy and weight loss

Two male patients [aged 53 and 54 years; body mass index (BMI) of 36.8 and 34.4 kg/m2] presented with severely symptomatic sleep apnea syndrome. Polysomnographic recording showed sleep fragmentation, diminution of stages III and IV and continuous sleep-related disordered breathing with mixed and obstructive apneas and hypopneas, and snoring. Apnea index (number of apneas per sleep-hour) was 73 and 30, respectively. These abnormalities were reversed by nasal continuous positive airway pressure (nCPAP). Home treatment with nCPAP associated with hypocaloric diet was started. Six months later, all symptoms had disappeared and BMI was 29 and 29.2 kg/m2, respectively. Polygraphic recordings without nCPAP showed regular breathing in all sleep stages, which were stable and normally abundant. Therapy has been discontinued and clinical and polygraphic data have remained normal for up to 6 and 11 months, respectively.     

Schlafbezogene Atmungsstörungen und zerebrovaskuläre Erkrankungen

Sleep-related breathing disorders comprise obstructive sleep apnea (OSA), central sleep apnea (CSA), Cheyne–Stokes respiration (CSR), and central alveolar hypoventilation. OSA is significantly associated with known cardiovascular risk factors, e.g., arterial hypertension, atrial fibrillation, and carotid atheromatosis. In addition, OSA has been shown to independently increase stroke risk. Thus, OSA is a direct and indirect risk factor of ischemic stroke, and early diagnosis and treatment of OSA may be crucial for stroke prevention. Acute ischemic stroke may cause any type of sleep-related breathing disorder in an affected patient. Nocturnal breathing abnormalities may be present transiently or persist for a longer period of time, affecting both neurological outcome and the risk of recurrent stroke. Sleep-disordered breathing is highly prevalent in patients with large supratentorial or bihemispheric infarctions, brainstem and cerebellar infarctions. It is associated with worse prognosis, increased disability, and higher mortality. Recently, several interventional studies showed that early implementation of continuous positive airway pressure (CPAP) treatment overnight is feasible and significantly improves neurological outcome in patients with ischemic stroke even if overall mortality may not be significantly reduced.     

Pharyngeal structure and function as a determinant of sleep-related breathing disorders: a unifying hypothesis

We propose a hypothesis which relates the pathogenesis of various sleep-related breathing disorders such as snoring, obstructive sleep apnea, and central sleep apnea to pharyngeal structure and function, i.e. pharyngeal area and compliance; these easily measured mechanical properties of the pharynx reflect the complex integrated response of upper airway muscles to changes in neural drive. Our arguments, although hypothetical, are based on the already existing measurements of pharyngeal dynamics in patients with sleep-related breathing disorders. If confirmed, this hypothesis would allow to predict a particular breathing disorder occurring during sleep from simple mechanical measurements performed in an awake subject, and furthermore it would help us to understand the effect of recent therapeutic modalities used in treatment of sleep apnea.     

Ventricular hypertrophy In sleep apnoea

SUMMARY  Ventricular hypertrophy is associated with an increased risk of cardiovascular death and cardiac events. In response to a haemodynamic load, ventricular hypertrophy may either be eccentric (dilation in response to volume overload) or concentric (increase in wall thickness in response to pressure overload). Ventricular hypertrophy increases with age, weight, blood pressure, and the presence of cardiovascular disease. It is greater in men than in women when adjusting for other variables. Echocardiography is the best method for accurate quantification of left ventricular mass and for detecting right ventricular hypertrophy. In obstructive sleep apnoea there are reports of both eccentric and concentric hypertrophy of the left ventricle. However, many of these reports have failed to control for patient weight or age. More recent reports indicate that much of the hypertrophy of the left ventricle reported in obstructive sleep apnoea can be related to patients' age, blood pressure, or size. However, right ventricular hypertrophy appears to be distinctly associated with the presence and severity of obstructive sleep apnoea. Right ventricular hypertrophy secondary to obstructive sleep apnoea may be the substrate for the eventual development of cor pulmonale and right heart failure. Its pathophysiological significance and potential use as a marker of severe OSA requires further investigation. Further investigation into left ventricular hypertrophy and sleep apnoea must control for the potentially confounding variables listed above and will require population-based and/or carefully matched case control studies.     

Cheyne-Stokes breathing and systemic arterial pressure periodic pattern during sleep in central alveolar hypoventilation

This report refers to a 51 year old man with the clinical features of central alveolar hypoventilation (CAH). Polysomnographic recordings showed periodic breathing and central apnoeas associated with abnormal oscillations of systemic arterial pressure and heart rate during all sleep stages. Oxygen administration during sleep reduced hypoxia, while the periodic breathing and arterial pressure oscillations persisted. The authors suggest that an impairment of the brain structures that play a role in homeostatic adjustment of autonomic functions in connection with the sleep-wake cycle, is responsible for the unusual sleep-related disturbances shown by this patient.     

Sleep-related sweating in obstructive sleep apnoea: association with sleep stages and blood pressure

The aim of this study was to investigate sleep-related sweating as a symptom of obstructive sleep apnoea (OSA). Fifteen otherwise healthy male non-smoking patients with untreated moderate-to-severe OSA underwent polysomnography, including measurements of skin and core body temperature and electrodermal activity (EDA) as an objective indicator of sweating. Evening and morning blood pressure was measured as well as catecholamines in nocturnal urine. All measurements were repeated after 3 months on successful continuous positive airway pressure (CPAP) treatment. The untreated OSA subjects had a mean (±SD) apnoea–hypopnoea index of 45.3 ± 3.9 and a mean EDA index during sleep of 131.9 ± 22.4 events per hour. Patients with higher EDA indices had higher systolic blood pressure in the evening and morning ( P  = 0.001 and 0.006) and lower rapid eye movement (REM) sleep percentage ( P  = 0.003). The EDA index decreased significantly to 78.5 ± 17.7 in the patients on CPAP treatment ( P  = 0.04). The decrease correlated with lower evening systolic and diastolic blood pressure ( P  = 0.05 and 0.006) and an increase in REM% ( P  = 0.02). No relationship was observed between EDA and skin or core body temperature, or to catecholamine levels in urine. OSA patients who experience sleep-related sweating may have increased blood pressure and decreased REM sleep compared with other OSA patients. CPAP treatment appears to lower blood pressure and increase REM sleep to a higher extent in these patients compared with other OSA patients.     

Cardiovascular risk among adults with obstructive sleep apnea syndrome

Cardiovascular diseases and sleep-disordered breathing have been recognized as a public health problem in Mexico and worldwide. These two groups of disorders are closely associated and the evidence accumulated over the last 25 years indicates that obstructive sleep apnea syndrome (OSAS) is an independent risk factor in systemic arterial hypertension, coronary artery disease and stroke. Other associations have also been described, linking these disorders with pulmonary hypertension, cardiac arrhythmias, sudden death during sleep and congestive heart failure. Treatment with continuous positive airway pressure in patients with OSAS has proven to be an efficient primary and secondary cardiovascular prevention strategy. This article reviews the epidemiological evidence that links OSAS with increased cardiovascular risk, and proposes strategies designed to address this growing health problem.     

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.     

Comparison of a novel non‐contact biomotion sensor with wrist actigraphy in estimating sleep quality in patients with obstructive sleep apnoea

Ambulatory monitoring is of major clinical interest in the diagnosis of obstructive sleep apnoea syndrome. We compared a novel non‐contact biomotion sensor, which provides an estimate of both sleep time and sleep‐disordered breathing, with wrist actigraphy in the assessment of total sleep time in adult humans suspected of obstructive sleep apnoea syndrome. Both systems were simultaneously evaluated against polysomnography in 103 patients undergoing assessment for obstructive sleep apnoea syndrome in a hospital‐based sleep laboratory (84 male, aged 55 ± 14 years and apnoea–hypopnoea index 21 ± 23). The biomotion sensor demonstrated similar accuracy to wrist actigraphy for sleep/wake determination (77.3%: biomotion; 76.5%: actigraphy), and the biomotion sensor demonstrated higher specificity (52%: biomotion; 34%: actigraphy) and lower sensitivity (86%: biomotion; 94%: actigraphy). Notably, total sleep time estimation by the biomotion sensor was superior to actigraphy (average overestimate of 10 versus 57 min), especially at a higher apnoea–hypopnoea index. In post hoc analyses, we assessed the improved apnoea–hypopnoea index accuracy gained by combining respiratory measurements from polysomnography for total recording time (equivalent to respiratory polygraphy) with total sleep time derived from actigraphy or the biomotion sensor. Here, the number of misclassifications of obstructive sleep apnoea severity compared with full polysomnography was reduced from 10/103 (for total respiratory recording time alone) to 7/103 and 4/103 (for actigraphy and biomotion sensor total sleep time estimate, respectively). We conclude that the biomotion sensor provides a viable alternative to actigraphy for sleep estimation in the assessment of obstructive sleep apnoea syndrome. As a non‐contact device, it is suited to longitudinal assessment of sleep, which could also be combined with polygraphy in ambulatory studies.     

New methods for the non-invasive assessment of sympathetic activity during sleep

Summary Autonomous nervous functions do change with normal sleep and do show characteristic changes with sleep disorders. This is why the investigation of autonomous nervous function during sleep plays an important role. Two different and new methods will be introduced here. The pulse transit time (PTT) determines the time delay between ECG and the resulting peripheral pulse wave. PTT is reverse proportional to arterial blood pressure and changes in amplitude of the PTT signal do correlate well with intra-thoracic pressure changes. The peripheral arterial tonometry (PAT) determines the peripheral arterial vascular tone using a plethysmographic method. The peripheral arterial tone is modulated by sympathetic and parasympathetic activity, by peripheral blood pressure, and by the peripheral resistance of the vessels. Both signals are non-invasive methods to assess changes of autonomous nervous function. With the help of both signals in addition to cortical arousal it is possible to detect sub-cortical arousal. This effect and the high correlation with oesophageal pressure and blood pressure changes result in characteristic changes in PTT and PAT for obstructive sleep apnoea. The changes are so characteristic that they can be used diagnostically. In summary, PTT and PAT do show different aspects of the autonomous nervous function and cannot be substituted by each other. Both give important additional information to characterise arousal during sleep and sleep disorders. The clinical and cardiovascular consequences of sub-cortical arousal need prospective long-term follow-up studies.     

Unterkieferprotrusionsschienen bei schlafbezogenen Atmungsstörungen

Continuous positive airway pressure (CPAP, automatic CPAP, APAP) is the standard therapy of obstructive sleep-related breathing disorders (oSDB). Mandibular advancement devices (MADs) can be used as alternatives to CPAP/APAP in mild to moderate obstructive sleep apnoea (OSA) (AHI?≤?30/h). This implies in particular the use of MADs in patients with a body mass index below 30?kg/m² and position-dependent OSA (pOSA). MADs can be considered in individual patients with severe OSA (AHI?>?30/h) if CPAP/APAP has been shown to be ineffective despite the full utilisation of all efforts of support. CPAP therapy can be provided by a qualified sleep physician immediately after confirmation of the diagnosis of oSDB. For the delivery of custom-made titratable oral appliances, the patient should be referred to a specialized dentist or orthodontist. Although there is a broad agreement on the indications for oral appliances, the rules of collaboration between sleep medicine and dentistry/orthodontics are not agreed upon. Therefore, the aim of this consensus paper is to describe the rules for the interdisciplinary collaboration that provides patients with MADs in North-Rhine Westphalia, Germany.     

The joint contribution of insomnia and obstructive sleep apnoea on sickness absence

Several studies have indicated a high degree of overlap between insomnia and obstructive sleep apnoea, but little is known regarding how the overlap may affect adverse outcomes associated with each of the disorders. The aim of the current study was to examine the separate and combined effects of symptoms of insomnia and obstructive sleep apnoea on long‐term sick leave. We used an historical cohort design with 4 years follow‐up. Information on sick leave was obtained from Norwegian official registry data, and merged with health information from the Hordaland Health Study in western Norway, 1997–99. A total of 6892 participants aged 40–45 years were assessed for self‐reported symptoms of insomnia and obstructive sleep apnoea (snoring and breathing cessations), as well as confounding factors. The level of overlap between insomnia and obstructive sleep apnoea was low (7–12%). Both insomnia and obstructive sleep apnoea alone were significant risk factors for subsequent sick leave after adjusting for confounding factors (odds ratios ranging from 1.4 to 2.3). Having comorbid insomnia and obstructive sleep apnoea increased the risk significantly. There was an additive interaction effect between the two conditions in the unadjusted analyses, but this was reduced to a non‐significant level when adjusting for confounders. This study is the first to report the separate and combined effects of insomnia and obstructive sleep apnoea on any adverse outcome. Having both insomnia and obstructive sleep apnoea increased the risk of later sick leave, but there was no evidence of an independent synergy effect of the two conditions.