睡眠呼吸暂停和肥厚型心肌病的关系

阻塞性睡眠呼吸暂停（OSA）是最常见的睡眠呼吸紊乱,与肥厚型心肌病（HCM）关系密切.OSA在HCM患者中普遍存在,而且OSA通过引起间歇性低氧血症反复激活交感神经系统,可以加重HCM患者的临床症状、恶化血流动力学指标和心功能状态;而且心房颤动与二者关系密切,在OSA与HCM之间扮演重要角色,积极发现并治疗OSA将可能改善HCM患者的临床症状和心血管预后,特别是对药物难治性HCM患者筛查并治疗OSA具有重要的意义.     

阻塞性睡眠呼吸暂停患者夜间及白日血压增高的机制

本文对阻塞性睡眠呼吸暂停(OSA)患者夜间及白日血压增高机制做一简要综述。OSA引起急性血压增高的机制可能与低氧血症、高碳酸血症、唤醒反应和OSA导致的交感神经活动改变及一些体液因子的变化有关。OSA长期后果可引起白日高血压发生,机制可能是通过颈动脉体功能失常、慢性间歇性低氧血症、交感神经活动增加、遗传和年龄等因素。     

应重视急性冠脉综合征的危险因素——睡眠呼吸暂停

睡眠呼吸暂停是指睡眠过程中由于上气道完全或部分阻塞和(或)呼吸中枢驱动降低导致呼吸暂停,从而产生慢性间歇性低氧、二氧化碳潴留、反复胸腔内压增大、反复微觉醒、睡眠结构异常、白天嗜睡、记忆力下降、自主神经功能紊乱等变化的一种全身性疾病.睡眠呼吸暂停包括阻塞性睡眠呼吸暂停(OSA)和中枢性睡眠呼吸暂停(CSA),临床上以OSA最为常见.     

睡眠呼吸暂停与心血管疾病的研究进展

阻塞性睡眠呼吸暂停(OSA)是一种常见病,表现为睡眠中反复发作呼吸暂停或呼吸减慢,导致肺换气不足,睡眠中反复惊醒和交感神经系统激活。研究发现,高血压、肥胖症、男性、种族因素、酒精、遗传因素及鼻腔阻塞等都参与了OSA的发生。夜间反复发生呼吸暂停或低通气,产生低氧血症和高碳酸血症,对心血管系统危害极大,引发多种心血管疾病。     

阻塞性睡眠呼吸暂停影响右心心肺耦联系统的研究进展

阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)是一种常见的睡眠呼吸紊乱性疾病,其特点是睡眠中上呼吸道塌陷从而出现反复的呼吸暂停或低通气。这种疾病伴随着夜间间歇性低氧、高碳酸血症、睡眠中断、打鼾和白天嗜睡等症状,其患病率在9%~38%之间,尤以中老年男性居多[1]。OSA通过促进交感神经系统激活、氧化应激、炎症反应、血管内皮功能受损等机制,导致动脉高压及心脏收缩和舒张功能障碍,增加了心血管疾病发生的风险[2]。由于夜间间断性低氧导致了OSA患者肺血管收缩和重构,肺动脉压力升高,右心室(right ventricular,RV)后负荷增加等一系列心肺耦联系统的损伤[3]。     

阻塞性睡眠呼吸暂停与癌症相关研究进展

阻塞性睡眠呼吸暂停(OSA)和癌症都是常见疾病。睡眠呼吸暂停发作时可伴有间歇低氧。研究表明, OSA的间歇性低氧可能影响肿瘤的发生, 而OSA与癌症的关系目前仍没有完全研究清楚, 阐明这个问题需要动物和细胞模型方面的实验以及人群的流行病学研究。该文就OSA与癌症相关的流行病学、病理生理、治疗进展等作一综述, 试图阐述OSA和癌症的关系。     

阻塞性睡眠呼吸暂停低通气综合征与心血管事件

随着"睡眠债"的出现及积累,阻塞性睡眠呼吸暂停低通气综合征崭露头角,并引起人们的关注。尽管它暂未纳入心血管风险评估中,但因它可引起或促进一系列心血管事件,已成为心血管死亡的预测器。其致心血管事件的主要病理生理机制涉及间歇性低氧血症和复氧、交感神经系统的激活、胸腔内压力的变化等。     

阻塞性睡眠呼吸暂停与慢性肾脏病研究进展

阻塞性睡眠呼吸暂停(obstructive sleep apnea, OSA)是一种常见的睡眠障碍,主要以夜间反复低氧血症、高碳酸血症、睡眠片段化和交感神经兴奋为特征.根据1993-2013年公布的流行病学数据显示,大约有17％的女性和22％的男性存在睡眠呼吸暂停指数(apnea hypopnea index,AHI)...     

阻塞性睡眠呼吸暂停血压升高的机制

阻塞性睡眠呼吸暂停（OSA）引起血压增高的机制可能与低氧血症，高碳酸血症，唤醒反应等所致的交感神经活动改变，体液因子，压力反射异常，血管重塑，内皮功能异常，遗传和年龄等因素共同参与有关。     

阻塞性睡眠呼吸暂停在关节置换术围手术期中的管理

正阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)是一个常见的但经常被忽视的呼吸睡眠失调性疾病。特征为睡眠时反复发作的部分或完全上气道阻塞引起的呼吸暂停或低通气~([1-2])。这种状况最终发生慢性间歇性低氧血症,导致疲乏、头疼、白天嗜睡、个性改变、心肺疾病、生活质量降低等~([3])。实际上,人们已经逐渐认识到OSA和高血压、糖尿病、代谢性疾病、心衰、冠状动脉性疾病、心律失常、中风、肺     

Obstructive sleep apnea: the new cardiovascular disease. Part I: obstructive sleep apnea and the pathogenesis of vascular disease

Obstructive sleep apnea (OSA) is increasingly recognized as a novel cardiovascular risk factor. OSA is implicated in the pathogenesis of hypertension, left ventricular dysfunction, coronary artery disease and stroke. OSA exerts its negative cardiovascular consequences through its unique pattern of intermittent hypoxia. Endothelial dysfunction, oxidative stress, and inflammation are all consequences of OSA directly linked to intermittent hypoxia and critical pathways in the pathogenesis of cardiovascular disease in patients with OSA. This review will discuss the known mechanisms of vascular dysfunction in patients with OSA and their implications for cardiovascular disease.     

Blood pressure effects of CPAP in nonresistant and resistant hypertension associated with OSA: A systematic review of randomized clinical trials

Obstructive sleep apnea (OSA) is a rather common chronic disorder, associated with increased prevalence of hypertension. The pathophysiological mechanisms for hypertension in OSA are at least in part linked to intermittent hypoxia developed during nightly hypopneas and apneas. Hypoxemia stimulates sympathetic overactivity, systemic inflammation, oxidative stress, and endothelial dysfunction. However, it appears that intermittent hypoxemia is not the only factor in the development of hypertension in OSA. Supplemental oxygen therapy that improved oxyhemoglobin saturation to similar levels to those achieved with CPAP treatment did not reduce BP. In this scenario, it could be proposed that hypoxemia acts as a trigger of sympathetic overdrive, which when set is the main factor in the development of hypertension in OSA. This review appraises evidence provided by randomized controlled trials on the BP-lowering effectiveness of continuous positive airway pressure (CPAP) treatment of OSA patients with nonresistant and resistant hypertension. It suggests that CPAP treatment is more effective in treating resistant hypertension than nonresistant hypertension. A possible explanation is that sympathetic overactivity and altered vascular reactivity in OSA could be more severe in resistant hypertension than in nonresistant hypertension. An intricate interaction among compliance, adherence, and their interaction with demographic characteristics, genetic factors, and comorbidities of the population included might explain the differences found between trials on their influence over the antihypertensive effectiveness of CPAP. Further long-term trials are needed in hypertensive OSA patients to assess whether CPAP treatment in OSA patients consistently restores physiological nocturnal BP fall and adjusts resting and circadian heart rate.     

Right and left ventricular functional impairment and sleep apnea.

Obstructive sleep apnea may contribute to the development of pulmonary hypertension and RVF primarily through pulmonary vasoconstriction secondary to hypoxia. Several recent studies indicate, however, that intermittent apnea-related hypoxia is not sufficient to cause sustained pulmonary hypertension. These studies have been consistent in showing that pulmonary hypertension and RVF are almost invariably seen in the presence of diurnal hypoxia. Sustained pulmonary hypertension, therefore, appears to be associated with sustained hypoxia as is the case in COPD. Patients with OSA who have hypoxia while awake are, as a rule, obese and have mild-to-moderate diffuse obstructive airways disease. Thus, most cases of pulmonary hypertension in association with OSA result from a combination of OSA, obesity, and diffuse obstructive airways disease, a so-called overlap syndrome. However, from the therapeutic viewpoint, it is apparent that treatment of OSA by NCPAP or tracheostomy, in such cases, is usually sufficient to reverse pulmonary hypertension and RVF. More recent work has provided strong evidence that OSA can play a role in the pathogenesis of LV heart failure in patients with CHF of otherwise unknown etiology. It is likely that this occurs through a combination of increased LV afterload related to exaggerated negative Pit swings during obstructive apneas, to intermittent hypoxia, and to chronically elevated sympathoadrenal activity. Reversal of OSA by NCPAP in these patients may relieve LV heart failure. These findings add a new dimension to our understanding of the pathophysiologic effects of OSA on the cardiovascular system by demonstrating that the LV is a structure that may suffer functional impairment secondary to the stresses imposed by OSA. Finally, it has now become apparent that CSR in patients with CHF can cause symptoms of a sleep apnea syndrome when associated with intermittent hypoxia and arousals from sleep. Reversal of CSR during sleep by NCPAP can lead to alleviation of these symptoms and possibly to reduced cardiac dyspnea and LV systolic function as well. Taken together, this suggests that much more extensive use of polysomnography may be warranted in the investigation of cardiovascular disease. The reasons are compelling: sleep apnea disorders are common and eminently treatable conditions whose reversal can result in improved right and left heart function and symptomatic improvement in patients with impaired myocardial function.     

Regulation of catecholamines by sustained and intermittent hypoxia in neuroendocrine cells and sympathetic neurons

Chronic intermittent hypoxia, a characteristic feature of sleep-disordered breathing, induces hypertension through augmented sympathetic nerve activity and requires the presence of functional carotid body arterial chemoreceptors. In contrast, chronic sustained hypoxia does not alter blood pressure. We therefore analyzed the biosynthetic pathways of catecholamines in peripheral nervous system structures involved in the pathogenesis of intermittent hypoxia-induced hypertension, namely, carotid bodies, superior cervical ganglia, and adrenal glands. Rats were exposed to either intermittent hypoxia (90 seconds of room air alternating with 90 seconds of 10% O2) or to sustained hypoxia (10% O2) for 1 to 30 days. Dopamine, norepinephrine, epinephrine, dihydroxyphenylacetic acid, and 5-hydroxytyptamine contents were measured by high-performance liquid chromatography. Expression of tyrosine hydroxylase and its phosphorylated forms, dopamine beta-hydroxylase, phenylethanolamine N-methyltransferase, and GTP cyclohydrolase-1 were determined by Western blot analyses. Both sustained and intermittent hypoxia significantly increased dopamine and norepinephrine content in carotid bodies but not in sympathetic ganglia or adrenal glands. In carotid bodies, both types of hypoxia augmented total levels of tyrosine hydroxylase protein and its phosphorylation on serines 19, 31, 40, as well as levels of GTP cyclohydrolase-1. However, the effects of intermittent hypoxia on catecholaminergic pathways were significantly smaller and delayed than those induced by sustained hypoxia. Thus, attenuated induction of catecholaminergic phenotype by intermittent hypoxia in carotid body may play a role in development of hypertension associated with sleep-disordered breathing. The effects of both types of hypoxia on expression of catecholaminergic enzymes in superior cervical neurons and adrenal glands were transient and small.     

Effect of episodic hypoxia on sympathetic activity and blood pressure

One of the major manifestations of obstructive sleep apnea (OSA) is profound and repeated (episodic) hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn directly increase sympathetic outflow. It is believed that this increase in sympathetic outflow is directly responsible, at least in part, for the acute blood pressure (BP) changes seen in OSA. It is difficult however, to study the chronic effects of repeated episodic hypoxia (EH) in humans since the chronic cardiovascular changes may take many years to manifest. For this reason, we developed a method of providing recurrent short periods of hypoxia (resembling the episodic desaturation in humans with OSA) to rats for 35 days, stimulating the chemoreceptors and the sympathetic nervous system, allowing examination of the chronic cardiovascular response to EH. The result of EH in rats is a 10-14 mmHg increase in resting (unstimulated) mean BP that lasts for several weeks after cessation of the daily EH. This BP increase is blocked by carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and the angiotensin-1 receptor blocker losartan. Thus, it appears that adrenergic and renin-angiotensin system over-activity contribute to the early chronic elevated BP in EH and perhaps in human hypertension associated with OSA.     

Sleep Apnea in Congestive Heart Failure

Obstructive sleep apnea (OSA) is a form of sleep disordered breathing in which pharyngeal muscle relaxation leads to recurrent nighttime apneas and hypopneas that, through increased afterload, intermittent hypoxia, and excess sympathetic activity, weaken the already failing heart. This review presents the current evidence regarding the complex relationship between OSA and heart failure (HF), including support for OSA as both a cause and consequence of HF. The impact of OSA on other cardiovascular diseases, such as hypertension, ischemic heart disease and arrhythmias, as they relate to HF development or exacerbation, also are reviewed.     

Vascular changes, cardiovascular disease and obstructive sleep apnea

Vascular changes related to obstructive sleep apnea (OSA) can lead to chronic cardiovascular consequences such as hypertension. The cardiovascular consequences are owing to nocturnal perturbations related to intrathoracic pressure changes, intermittent hypoxia, sympathetic neural activation, endothelial dysfunction, oxidative stress and systemic inflammation. Intermittent hypoxia due to sleep-related events in OSA activates the renin-angiotensin system and increases the levels of endothelin-1. Intermittent hypoxia also results in oxidative stress, as evidenced by elevated levels of xanthine oxidoreductase, lipid peroxidation and the presence of reactive oxygen species. There is also evidence for a decrease in antioxidant capacity. Patients with OSA may have endothelial dysfunction that resolves with continuous positive airway pressure. OSA is a state of inflammation as evidenced by elevated levels of C-reactive protein, IL-6, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin. This may suggest that OSA is a predisposing factor for atherogenesis. This article will discuss the role of nocturnal perturbations consequent to OSA resulting in endothelial dysfunction, oxidative stress, and inflammation and how they may subsequently play a causative role in cardiovascular disorders.     

Obesity, obstructive sleep apnoea and metabolic syndrome

OSA is increasingly recognized as a major health problem in developed countries. Obesity is the most common risk factor in OSA and hence, the prevalence of OSA is undoubtedly rising given the epidemic of obesity. Recent data also suggest that OSA is highly associated with the metabolic syndrome, and it is postulated that OSA contributes to cardiometabolic dysfunction, and subsequently vasculopathy. Current evidence regarding the magnitude of impact on ultimate cardiovascular morbidity or mortality attributable to OSA-induced metabolic dysregulation is scarce. Given the known pathophysiological triggers of intermittent hypoxia and sleep fragmentation in OSA, the potential mechanisms of OSA-obesity-metabolic syndrome interaction involve sympathetic activation, oxidative stress, inflammation and neurohumoral changes. There is accumulating evidence from human and animal/cell models of intermittent hypoxia to map out these mechanistic pathways. In spite of support for an independent role of OSA in the contribution towards metabolic dysfunction, a healthy diet and appropriate lifestyle modifications towards better control of metabolic function are equally important as CPAP treatment in the holistic management of OSA.     

Genomics of sleep-disordered breathing

The technologies of genomics and proteomics are powerful tools for discovering novel gene and protein expression responses to disease. Considerable evidence indicates that a genetic basis exists to the causes of sleep-disordered breathing, in particular its most common form of obstructive sleep apnea (OSA), which is characterized by periods of intermittent hypoxia and disrupted sleep. However, the genetic contribution to the pathogenesis of OSA has largely been determined using traditional genetic approaches of family, twin, and linkage studies in clinical populations and quantitative trait loci and targeted gene procedures in animal models of OSA. In contrast to the pathogenesis of OSA, the consequences or sequelae of OSA are highly amenable to genomic and proteomic approaches. Animal studies have assessed changes in gene and protein expression in multiple organ systems in response to intermittent hypoxia and sleep deprivation and uncovered novel gene activation paradigms. The first tentative steps have been made toward applying proteomic analyses of blood and urine from patients with OSA as a potential screening tool for diagnosis in the clinical setting. It is anticipated that genomic and proteomic technologies will become increasingly used in the area of OSA with the unprecedented access to tissue in procedures such as bariatric surgery. OSA represents a severe insult to the oxygenation of tissues and the homeostasis of sleep, and genomic and proteomic approaches hold promise for defining previously unexplored mechanisms and pathways that lead to downstream pathologies, including hypertension, insulin resistance, and neurocognitive dysfunction.     

阻塞型睡眠呼吸暂停低通气综合征相关高血压的诊治进展

阻塞型睡眠呼吸暂停低通气综合征(OSAHS)与高血压的关系非常密切,目前研究认为OSAHS是继发性高血压中非常常见的原因,是难治性高血压的主要原因。OSAHS引起高血压的机制比较复杂,多种机制参与了高血压的发生,其中OSAHS患者睡眠紊乱可能是引起交感神经活性增强以及间歇性低氧的重要原因。OSAHS相关高血压的诊断主要依靠多导睡眠监测和血压的测量。持续气道正压治疗是OSAHS患者首选的治疗方法,对于OSAHS合并高血压的患者,在临床上也应当注意醛固酮拮抗剂、口腔矫正器以及呼吸肌肉训练的使用。