Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea

Background

Obstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP).

Results

Of the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR), brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02) and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03) after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin.

Conclusions

Patients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.     

Women and sleep

Naturally fluctuating hormones (menstrual cycle, through pregnancy or menopausal transition) are not related to marked sleep disturbances in women. It is likely, however, that subsets of women will display a central nervous system vulnerability to hormonal fluctuations so that sleep disturbances manifest as a part of a complex of discomforting symptoms. Sleep is impacted directly through the circadian system or brain sleep regulation or through the development of concurrent functional changes and symptoms. Women are susceptible to sleep-related disorders that are also common in men, such as primary insomnia and SBD although the contributing factors and manifestations may not be the same.     

Endocrine disturbances in sleep apnea syndrome

Sleep apnea may interact endocrine rhythms by a number of mechanisms. Repetitive apneas will cause sleep fragmentation and disorganization of sleep stages and cycles. How this compares with hormonal changes secondary to sleep deprivation is unclear. Hypoxia may have direct central effects on neurotransmitters, which in turn will affect hypothalamic-pituitary hormone production. And, sudden arousal from sleep may produce a central stress response leading to hormonal changes. These factors may interact and lead to changes in the central of sleep and endocrine rhythms. We describe Growth hormone and Androgens secretion during sleep with obstructive sleep apnea patients.     

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is a common medical condition that occurs in approximately 5% to 15% of the population. The pathophysiology of OSA is characterized by repetitive occlusions of the posterior pharynx during sleep that obstruct the airway, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, and termination by arousal from sleep. Obstructive sleep apnea is associated with daytime sleepiness and fatigue, likely due to fragmented sleep from recurrent arousals. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA and that OSA is a risk factor for the development of hypertension. Recent studies show that OSA may be implicated in stroke and transient ischemic attacks. Obstructive sleep apnea appears to be associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with preexisting pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified to be important in the development of atherosclerosis. Obstructive sleep apnea is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, and plasminogen activator inhibitor, and reduced fibrinolytic activity. Obstructive sleep apnea has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.     

The relationship between sleep disorders and stroke

Although sleep appears to be a quiescent, passive state externally, there are a multitude of physiological changes occurring during sleep that can affect cerebral homeostasis and predispose individuals to cerebrovascular disorders. Therefore, it is not surprising that sleep-disordered breathing causes significant nocturnal perturbations, such as obstructive sleep apnea (OSA), that can lead to cerebrovascular disorders. There is evidence to suggest that OSA is a risk factor for stroke, although studies have not been able to clearly discern the absence or presence of OSA before the stroke event. Sleep-disordered breathing, such as OSA and central sleep apnea, can occur as a consequence of stroke. Fortunately, treating OSA appears to decrease morbidity and possibly mortality. Unfortunately, continuous positive airway pressure compliance in this population group is low, and significant efforts and resources may be needed to improve compliance and adherence. Various other sleep disorders, such as insomnia, fatigue, hypersomnia, and parasomnia, can occur following a stroke, and physicians treating patients following a stroke need to be aware of these disorders in order to effectively treat such patients.     

Increased brain activation during verbal learning in obstructive sleep apnea

This study examined the cerebral response to a verbal learning (VL) task in obstructive sleep apnea (OSA) patients. Twelve OSA patients and 12 controls were studied with functional magnetic resonance imaging (FMRI). As hypothesized, VL performance was similar for both groups, but OSA patients showed increased brain activation in several brain regions. These regions included bilateral inferior frontal and middle frontal gyri, cingulate gyrus, areas at the junction of the inferior parietal and superior temporal lobes, thalamus, and cerebellum. Better free recall performance in the OSA group was related to increased cerebral responses within the left inferior frontal gyrus and left supramarginal area. Recall was negatively related to activation within the left inferior parietal lobe. The findings support the predictions that intact performance in OSA patients is associated with increased cerebral response. Recruitment of additional brain regions to participate in VL performance in OSA patients likely represents an adaptive compensatory recruitment response, similar to that observed in young adults following total sleep deprivation and in healthy older adults. These data, and those of the only other FMRI study in OSA, suggest that individuals with OSA show characteristic differences in the BOLD signal response to cognitive challenges. Including subjects with untreated OSA in neuroimaging studies may potentially influence the results by altering individual and group level activation patterns. Given this, future neuroimaging studies may want to be aware of this potential confound.     

Sleep and medical disorders

Extensive evidence links cardiovascular disease and sleep disordered breathing. OSA has adverse effects on blood pressure, cardiovascular status,and mortality. Effective CPAP therapy can improve blood pressure and cardiac function in patients who have OSA. Patients who have congestive heart failure have a high prevalence of sleep-disordered breathing, with OSA occurring in 30% of such patients and Cheyne-Stokes respiration in 40%.CPAP is the preferred mode of therapy for both types of sleep-disordered breathing in patients who have coexistent congestive heart failure. Nocturnal worsening of asthma is a common manifestation of this disease that indicates increased disease severity. Therapy focuses on judicious use of long-acting bronchodilators, and the presence of OSA should also be considered. COPD is frequently associated with impaired sleep, likely because of chronic dyspnea and sleep-associated hypoxemia. Appropriate therapy again includes long-acting bronchodilators and possibly nocturnal supplemental oxygen.Gastroesophageal reflux during sleep may lead to prolonged episodes of esophageal acid exposure and may be a common sequela of OSA, perhaps triggering nocturnal worsening of asthma. Endstage renal disease and chronic dialysis are commonly associated with a host of troublesome sleep problems,including OSA, RLS, PLMD, and daytime sleepiness.     

Sleep, sleep loss, and breathing

Sleep and sleep loss have remarkable effects on breathing. Although sleep causes ventilatory disturbances of greater severity and variety than does sleep deprivation, the effects of sleep and sleep loss on respiration are similar. For example, both impair ventilatory drive and arousal responses to a variety of stimuli. Although the mechanism of impaired ventilation after sleep loss is not entirely understood, there is evidence to suggest that both respiratory muscle fatigue and central nervous system depression play a role. Patients who suffer from both disturbed sleep and lung disease are particularly vulnerable to the adverse effects of sleep disruption on breathing. Since sleep restoration returns many respiratory parameters to normal in sleep-deprived individuals, perhaps we should include rest in our treatment of certain patients with respiratory disease.     

Improving Provider AASM Guideline Adherence for Adult Obstructive Sleep Apnea

With an estimated 10% of the United States adult population impacted by obstructive sleep apnea (OSA), a protocol was created to increase clinical provider adherence to the American Academy of Sleep Medicine’s Clinical Guidelines for OSA. Clinic provider responsibilities included screening patients ≥ 18 years old using the Epworth Sleepiness Scale (ESS), referring patients scoring > 9 for a sleep study, educating patients diagnosed with OSA regarding disease and treatment options, prescribing treatment and short-term follow-up. After providing education and resources, 72% of patients ≥ 18 years of age were screened and 19 patients with a positive screen and OSA diagnosis had reduced OSA severity after treatment.     

Obstructive sleep apnoea causes transient and sustained systemic hypertension

Apnoea with associated fall in arterial oxygen tension results in increased blood pressure and a striking surge in sympathetic activity, which can be measured as high catecholamine levels or increase in muscle sympathetic nerve activity. Following the termination of apnoea with resumption of breathing, sympathetic nerve activity decreases and blood pressure returns to lower values. Sympathetic mediated alternations in peripheral vascular resistance best explain these findings. Hypertension during wakefulness in untreated patients with apnoea is also associated with high sympathetic nervous system activity. Nasal continuous positive airway pressure (CPAP) has been shown to lower blood pressure in some hypertensive obstructive sleep apnoea (OSA) patients. Recently, previously untreated OSA patients exhibiting awake sympathetic hyperexcitation demonstrated striking attentuation of the response following initiation of effective CPAP therapy. Accordingly, the common problem of systemic hypertension found in untreated OSA appears to be mediated by sympathetic excitation and responds to effective CPAP therapy.     

Fibromyalgia and Sleep in Animal Models: A Current Overview and Future Directions

Sleep disorders are highly prevalent in patients with fibromyalgia (FM). Many of the daytime symptoms, such as chronic pain and fatigue, may be related to the non-restorative sleep patterns associated with the disease. Pain influences the sleep process and sleep disturbances decrease the pain threshold in a reciprocal framework. Thus, understanding the link between sleep and FM has become an important research topic in basic science. Therefore, in the current review we connect these topics and provide some insights into the cyclic relationship between sleep and pain, which has been addressed mainly in animal models. Additionally, we highlight the urgent need for sleep studies in FM animal models, which might improve the knowledge base and accelerate advances in this field.     

Obtaining a thorough sleep history and routinely screening for obstructive sleep apnea

PURPOSE: To present a clinical case study of obstructive sleep apnea (OSA) and discuss a potential correlation between OSA, unexplained distal pain symptoms, and pyschoemotional concerns. DATA SOURCES: A review of the scientific literature was performed on OSA using the Cumulative Index of Nursing and Allied Health Literature and MEDLINE. CONCLUSIONS: OSA is potentially life threatening and can have serious consequences to a patient's health. Many of the obvious signs of OSA occur at night, and the symptoms of OSA may correspond to a variety of other diseases. Clinicians should recognize a possible correlation between OSA and unexplained distal pain symptoms as well as psychoemotional concerns. These clinically associated conditions may be less apparent but may dramatically affect quality of life. By improving recognition and treatment of OSA, morbidity and mortality can be reduced and quality of life can be improved for patients and their families. IMPLICATIONS FOR PRACTICE: It is imperative that clinicians are attentive and take detailed histories to recognize the clinical signs and symptoms of OSA, paying more attention to the less obvious symptomatology that may be significantly impacting quality of life.     

Sleep disorders associated with traumatic brain injury

OBJECTIVES: To investigate the frequency of sleep disorders in traumatic brain injury (TBI) patients with hypersomnia and to discern the relationship between posttraumatic sleep disorders and pretraumatic sleep symptoms. DESIGN: Prospective cohort study using the criterion standard to diagnose sleep disorders in a consecutive sample of TBI patients. SETTING: Academic medical center with level I trauma center, rehabilitative medicine services, and accredited sleep disorders center. PATIENTS: Ten TBI patients with subjective excessive sleepiness. INTERVENTION: Nocturnal polysomnography followed by Multiple Sleep Latency Test. Subjects who had overt sleep apnea on the first nocturnal polysomnography had a second nocturnal polysomnography with titration of nasal continuous positive airway pressure. MAIN OUTCOME MEASURES: Diagnosis of sleep-disordered breathing, narcolepsy, and posttraumatic hypersomnia. RESULTS: A diagnosis of treatable sleep disorder was made in all 10 subjects. Sleep-disordered breathing was found in 7 subjects: overt obstructive sleep apnea (OSA) was diagnosed in 5 subjects, rapid eye movement-related OSA in 1, and upper airway resistance syndrome (UARS) in 1. Narcolepsy was diagnosed in 2 subjects, and the diagnosis of posttraumatic hypersomnia was made in 1 subject. Three subjects had symptoms of hypersomnia before their injury (1 each with narcolepsy, OSA, UARS), and 2 of these were driving a car at the time of injury. CONCLUSION: Treatable sleep disorders appear to be common in the sleepy TBI population, but may be largely undiagnosed and untreated.     

嗜血细胞综合征累及中枢神经系统的临床特征

【目的】探讨成人嗜血细胞综合征（HPS）累及中枢神经系统的临床特征。【方法】回顾性分析2例诊断为HPS累及中枢神经系统患者的临床特征。【结果】中枢神经系统症状一般在病程晚期出现,表现为各种各样的神经系统症状,脑脊液改变是非特异的,最常见的神经影像学表现是弥漫性脑萎缩伴局灶坏死和脑白质的异常。增强后可见广泛的软脑膜强化及血管周围间隙强化。【结论]HPS累及中枢神经系统的临床表现和神经影像学无特异性,与中枢神经系统感染、急性播散性脑脊髓炎、多发性硬化等疾病不易鉴别。     

Headache and sleep disorders: review and clinical implications for headache management

Review of epidemiological and clinical studies suggests that sleep disorders are disproportionately observed in specific headache diagnoses (eg, migraine, tension-type, cluster) and other nonspecific headache patterns (ie, chronic daily headache, "awakening" or morning headache). Interestingly, the sleep disorders associated with headache are of varied types, including obstructive sleep apnea (OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and hypersomnia. Headache, particularly morning headache and chronic headache, may be consequent to, or aggravated by, a sleep disorder, and management of the sleep disorder may improve or resolve the headache. Sleep-disordered breathing is the best example of this relationship. Insomnia is the sleep disorder most often cited by clinical headache populations. Depression and anxiety are comorbid with both headache and sleep disorders (especially insomnia) and consideration of the full headache-sleep-affective symptom constellation may yield opportunities to maximize treatment. This paper reviews the comorbidity of headache and sleep disorders (including coexisting psychiatric symptoms where available). Clinical implications for headache evaluation are presented. Sleep screening strategies conducive to headache practice are described. Consideration of the spectrum of sleep-disordered breathing is encouraged in the headache population, including awareness of potential upper airway resistance syndrome in headache patients lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep regulation strategies are offered that are also compatible with treatment of primary headache.     

Inflammatory aspects of sleep apnea and their cardiovascular consequences

Obstructive sleep apnea (OSA) is a common medical condition that occurs in a considerable percentage of the population. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA, and that OSA is a risk factor for the development of hypertension. It is established that OSA may be implicated in stroke and transient ischemic attacks. OSA is associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with pre-existing pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified as important in the development of atherosclerosis. OSA is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor, and reduced fibrinolytic activity. OSA has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.     

Clonidine and sleep apnea syndrome interaction: antagonism with yohimbine

A patient with sleep apnea syndrome, concurrently taking clonidine as an antihypertensive, presented with severe respiratory acidosis, hypotension, and associated central nervous system depression. Acidosis was improved by mechanical ventilation, and central nervous system (CNS) depression and hypotension were reversed with yohimbine. Clonidine may have an additive CNS depressive effect in sleep apnea syndrome and should be used with caution in such patients. Yohimbine’s sympathetic-enhancing effects may be useful in clonidine toxic states.     

睡眠体位对睡眠呼吸暂停低通气综合征患者呼吸功能的影响

背景阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)低通气患者的呼吸紊乱严重度与睡眠体位有关,根据呼吸暂停低通气指数(AHI)将OSA患者分为体位型和非体位型两种类型.目的比较体位型与非体位型OSA患者的临床特征,探讨睡眠体位与OSA患者呼吸功能的关系.设计以OSA患者为研究对象的观察对比研究.单位南京军区南京总医院的睡眠呼吸监测中心.对象选择1998-10/2002-05在南京军区南京总医院呼吸内科睡眠呼吸监测室就诊并行整夜多导睡眠仪检查的患者共225例.纳入标准①AHI≥l0次/h者,②平卧位及侧卧位睡眠时间≥30 min者,③年龄≥20岁者.排除标准①年龄＜20岁者,②患重大躯体疾病者.其中63例为体位型,162例为非体位型.方法所有患者均接受整夜多导睡眠仪检查,同时详询患者病史和进行体格检查,应用体积描计仪进行呼吸功能测定.比较体位型与非体位型两组患者的一般临床特征、肺功能参数及多导睡眠图资料.应用多元逐步回归分析探讨决定患者为体位型或非体位型的因子.主要观察指标主要结局两组患者的临床资料、多导睡眠图资料及肺功能比较.次要结局OSA患者的分型与临床资料各项目的相关性.结果225例OSA患者中体位型患者共63例(28%),体位组和非体位组患者体质量指数分别(27.97±3.21),(26.22±2.72)kg/m 2(t=3.977,P＜0.01).两组多导睡眠图资料比较,体质量指数匹配前除侧卧位睡眠时间、平卧位睡眠时间、侧卧位最低血氧饱和度及基础血氧饱和度外,其他项目两组间差异均有显著性意义(P＜0.05或P＜0 01);匹配后除两组夜间肢体运动次数差异无显著意义外,其余结果与原始组比较结果相同.两组肺功能参数间差异无显著性意义(P＞0.05).多元逐步回归分析显示,决定为体位或非体位患者的主要因子为AHI和体质量指数,两因子的预测能力为26.2%;直线相关分析结果表明,在全组及非体位组患者,睡眠呼吸紊乱度(AHI及血氧饱和度)与体质量指数显著相关(P＜0.05或P＜0.01),而在体位组,两者无相关关系(P＞0.05).结论约1/3的OSA患者可归类为体位型,这类患者应对睡眠姿势训练治疗反应良好,可以保留足够的上气道通畅性,减轻睡眠呼吸阻塞程度,改善患者的呼吸功能.     

New concepts in primary fibrositis syndrome

PFS is a painful rheumatologic disorder that may be detected by the wary clinician attuned to the presence of seven or more tender points. This common disorder may be seen at any age, including childhood, and may be associated with secondary symptoms of depression and other affective disorders. It may also be associated with findings of disturbed sleep, hearing and vestibular abnormalities, and profound complaints of fatigue. The vagueness of this latter complaint means that PFS must be distinguished from the newly described CEBV syndrome. Although the etiology of PFS remains unknown, recent investigations suggest that these patients may suffer a disorder with a central nervous system component as well as a subtle peripheral tissue lesion. Newer PFS studies demonstrate tissue changes that may be consistent with altered microvascular permeability and blood flow, tissue hypoxia, and chronic muscle spasm. An immunologic abnormality, or even a previously undescribed connective tissue disease, may be important as a pathogenic factor in some PFS patients.     

Abdominal fat and sleep apnea: the chicken or the egg?

Obstructive sleep apnea (OSA) syndrome is a disorder characterized by repetitive episodes of upper airway obstruction that occur during sleep. Associated features include loud snoring, fragmented sleep, repetitive hypoxemia/hypercapnia, daytime sleepiness, and cardiovascular complications. The prevalence of OSA is 2-3% and 4-5% in middle-aged women and men, respectively. The prevalence of OSA among obese patients exceeds 30%, reaching as high as 50-98% in the morbidly obese population. Obesity is probably the most important risk factor for the development of OSA. Some 60-90% of adults with OSA are overweight, and the relative risk of OSA in obesity (BMI >29 kg/m(2)) is >or=10. Numerous studies have shown the development or worsening of OSA with increasing weight, as opposed to substantial improvement with weight reduction. There are several mechanisms responsible for the increased risk of OSA with obesity. These include reduced pharyngeal lumen size due to fatty tissue within the airway or in its lateral walls, decreased upper airway muscle protective force due to fatty deposits in the muscle, and reduced upper airway size secondary to mass effect of the large abdomen on the chest wall and tracheal traction. These mechanisms emphasize the great importance of fat accumulated in the abdomen and neck regions compared with the peripheral one. It is the abdomen much more than the thighs that affect the upper airway size and function. Hence, obesity is associated with increased upper airway collapsibility (even in nonapneic subjects), with dramatic improvement after weight reduction. Conversely, OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. OSA is associated with increased sympathetic activation, sleep fragmentation, ineffective sleep, and insulin resistance, potentially leading to diabetes and aggravation of obesity. Furthermore, OSA may be associated with changes in leptin, ghrelin, and orexin levels; increased appetite and caloric intake; and again exacerbating obesity. Thus, it appears that obesity and OSA form a vicious cycle where each results in worsening of the other.