持续气道正压通气对于阻塞性睡眠呼吸暂停相关性高血压的治疗效果研究进展

阻塞性睡眠呼吸暂停常影响睡眠质量并引起心血管疾病,其中高血压发病率最高。目前对于阻塞性睡眠呼吸暂停与高血压之间的关系及机制仍在探索中,而持续气道正压通气作为阻塞性睡眠呼吸暂停的有效治疗方法,对于血压的降压作用说法不一。了解阻塞性睡眠呼吸暂停与高血压之间的关系机制及持续气道正压通气的治疗效果,将有助于更好的临床实践。     

Causes and consequences of blood pressure alterations in obstructive sleep apnea

The obstructive sleep apnea (OSA) syndrome has been considered to be a cause of both transient blood pressure elevations during sleep and sustained hypertension during the awake state. The purpose of this review was to examine critically the existing literature regarding (1) the blood pressure alterations associated with OSA, (2) causal mechanisms relating specific blood pressure alterations to OSA, and (3) potential consequences of the systemic circulatory abnormalities associated with OSA. Particular attention was directed at studies that assessed the prevalence of OSA in patients with hypertension and that examined the effects on blood pressure of treatment of OSA. We conclude that patients with OSA have abnormal sleep blood pressure patterns, manifested most frequently by apnea-associated blood pressure elevations. Confounding factors such as obesity and antihypertensive drug therapy, and conflicting evidence regarding changes in daytime blood pressure after therapy for OSA, make it premature to conclude that OSA and daytime hypertension are directly associated. Circumstantial evidence suggests that the blood pressure alterations that occur during sleep could contribute to the high cardiovascular morbidity in patients with OSA. Further research into the relationship between OSA and hypertension should improve the future care of patients with these conditions and enhance our understanding of cardiopulmonary pathophysiology.     

OSA and cardiometabolic risk: What's the bottom line?

Obstructive sleep apnoea (OSA) is a common condition characterized by repetitive upper airway obstruction during sleep. OSA promotes wide intrathoracic pressure swings, intermittent hypoxia and sleep fragmentation. Growing evidence derived from animal models mimicking the oxygen profile observed in patients with OSA as well as clinical studies support that this important sleep‐disordered breathing is associated with increased cardiovascular risk. Although the precise mechanisms are not fully established, it is conceivable that the metabolic deregulation promoted by the components of OSA may have an important causal role in the poor cardiovascular prognosis. In this review, we summarize the potential role of OSA and its components on cardiometabolic disease. We also summarize evidence evaluating the impact of OSA treatment (notably continuous positive airway pressure) on reversing the metabolic deregulation promoted by OSA. Finally, we discuss the research agenda and perspectives for this important research area.     

Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications

Obstructive sleep apnea (OSA) exposes the cardiovascular system to intermittent hypoxia, oxidative stress, systemic inflammation, exaggerated negative intrathoracic pressure, sympathetic overactivation, and elevated blood pressure (BP). These can impair myocardial contractility and cause development and progression of heart failure (HF). Epidemiological studies have shown significant independent associations between OSA and HF. On the other hand, recent prospective observational studies reported a significant association between the presence of moderate to severe OSA and increased risk of mortality in patients with HF. In randomized trials, treating OSA with continuous positive airway pressure suppressed sympathetic activity, lowered BP, and improved myocardial systolic function in patients with HF. These data suggest the potential for treatment of OSA to improve clinical outcomes for patients with HF. However, large-scale randomized trials with sufficient statistical power will be needed to ascertain whether treatment of OSA will prevent development of, or reduce morbidity and mortality from HF.     

Obesity, sleep apnea, and hypertension

Obesity has a high and rising prevalence and represents a major public health problem. Obstructive sleep apnea (OSA) is also common, affecting an estimated 15 million Americans, with a prevalence that is probably also rising as a consequence of increasing obesity. Epidemiologic data support a link between obesity and hypertension as well as between OSA and hypertension. For example, untreated OSA predisposes to an increased risk of new hypertension, and treatment of OSA lowers blood pressure, even during the daytime. Possible mechanisms whereby OSA may contribute to hypertension in obese individuals include sympathetic activation, hyperleptinemia, insulin resistance, elevated angiotensin II and aldosterone levels, oxidative and inflammatory stress, endothelial dysfunction, impaired baroreflex function, and perhaps by effects on renal function. The coexistence of OSA and obesity may have more widespread implications for cardiovascular control and dysfunction in obese individuals and may contribute to some of the clustering of abnormalities broadly defined as the metabolic syndrome. From the clinical and therapeutic perspectives, the presence of resistant hypertension and the absence of a nocturnal decrease in blood pressure in obese individuals should prompt the clinician to consider the diagnosis of OSA, especially if clinical symptoms suggestive of OSA (such as poor sleep quality, witnessed apnea, excessive daytime somnolence, and so forth) are also present.     

Obstructive sleep apnea and cardiovascular disease - time to act!

Sleep related breathing disorders are common and their potential to disrupt sleep leading to daytime fatigue and hypersomnolence is widely acknowledged. In the future, obstructive sleep apnoea (OSA) may become even more important because obesity as a main risk factor is increasingly prevalent. Apart from disturbing sleep, OSA has also been recognised as a risk factor for hypertension, acute cardiovascular events and metabolic disturbance such as insulin resistance. Several randomised controlled trials demonstrated a positive effect of nasal continuous positive airway pressure (CPAP) treatment on arterial blood pressure, leading the "Joint National Council on High Blood Pressure" to list obstructive sleep apnoea as the first identifiable cause of arterial hypertension. Recently, a growing body of evidence demonstrated also a risk reduction of fatal and non-fatal cardiovascular events by treatment of obstructive sleep apnoea. A beneficial effect of treatment of OSA was also shown for patients with heart failure, or heart rhythm disturbance. Obstructive sleep apnoea may no longer be seen as a cause for daytime sleepiness and impaired quality of life only, but also as an independent risk factor, at least for the occurrence of hypertension but probably for any cardiovascular and cerebrovascular disease. While prospective controlled trials to document a reduction of cardiovascular morbidity and mortality are awaited, therapeutic nihilism seems no longer appropriate. With effective treatment available, subgroups that may profit best remain to be identified.     

Hypertension research in sleep apnea

Obstructive sleep apnea (OSA) is characterized by repetitive partial and total collapse of the upper airway that induces stressful arousals throughout sleep to reestablish breathing. Although estimates vary, prevalence has been reported as high as 20% in the adult population. OSA is common in several chronic diseases, the most common of which is obesity. Evidence is strong that OSA increases the risk of hypertension and both fatal and nonfatal cardiovascular events. Several mechanisms linking OSA to hypertension have been proposed, with increased sympathetic activation implicated as the prime mediator. This review summarizes recent data on the influence of OSA on blood pressure, the effect of standard OSA therapy on improving blood pressure, and the potential of lifestyle modification for further decreasing hypertension risk. Challenges confronting the investigation of blood pressure outcomes in response to treatment in OSA patients are discussed.     

The multisystemic effects of oral appliance therapy for obstructive sleep apnea: A narrative review

Obstructive sleep apnea (OSA) is a chronic condition accompanied by repeated obstruction of the upper airway during sleep despite respiratory efforts, resulting in intermittent hypoxemia, altered sleep structure, and sympathetic activation. Previous studies have shown a significant association between OSA and general health issues such as cardiovascular diseases, endocrine disorders, neurocognitive function decline, and poor quality of life. Continuous positive airway pressure (CPAP) has been considered as the first line treatment for OSA. However, accumulating evidence supports the role of oral appliance (OA) therapy, including mandibular advancement devices, as an alternative option for snoring and OSA patients who do not comply with or refuse CPAP usage. Despite a generally favorable outcome of OA therapy for OSA related respiratory indices, studies focusing on the impact of systemic effects of OA therapy in OSA patients are relatively scarce compared with the extensive literature focusing on the systemic effects of CPAP. Therefore, this article aimed to provide an overview of the current evidence regarding the multisystemic effects of OA therapy for OSA.     

Obstructive sleep apnea therapy for cardiovascular risk reduction—Time for a rethink?

Obstructive sleep apnea (OSA) is a highly prevalent and underdiagnosed medical condition, which is associated with various cardiovascular and metabolic diseases. The current mainstay of therapy is continuous positive airway pressure (CPAP); however, CPAP is known to be poorly accepted and tolerated by patients. In randomized controlled trials evaluating CPAP in cardiovascular outcomes, the average usage was less than 3.5 hours, which is below the 4 hours per night recommended to achieve a clinical benefit. This low adherence may have resulted in poor effectiveness and failure to show cardiovascular risk reduction. The mandibular advancement device (MAD) is an intraoral device designed to advance the mandible during sleep. It functions primarily through alteration of the jaw and/or tongue position, which results in improved upper airway patency and reduced upper airway collapsibility. The MAD is an approved alternative therapy that has been consistently shown to be the preferred option by patients who are affected by OSA. Although the MAD is less efficacious than CPAP in abolishing apnea and hypopnea events in some patients, its greater usage results in comparable improvements in quality‐of‐life and cardiovascular measures, including blood pressure reduction. This review summarizes the impact of OSA on cardiovascular health, the limitations of CPAP, and the potential of OSA treatment using MADs in cardiovascular risk reduction.     

交感神经兴奋在慢性间歇性低氧引起高血压发生过程中的作用

交感神经活性增强在阻塞性睡眠呼吸暂停引起的高血压及其他心血管疾病发生过程中起到重要作用.阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)最为明显的特征就是夜间反复的间歇 性低氧,这种间歇性低氧状态对于交感神经激活及血压升高显得尤为重要.以下就OSA相关性间歇性低氧引起的交感神经系统激活以及其...     

Sleep disorders in patients with congestive heart failure

PURPOSE OF REVIEW: This review of recent literature pertains to the growing evidence that obstructive sleep apnea contributes to the development of systemic hypertension and congestive heart failure. RECENT FINDINGS: There is irrefutable evidence that OSA causes systemic hypertension and that continuous positive airway pressure (CPAP) treatment of OSA causes a reduction in blood pressure. Moreover there is evidence that untreated OSA is associated with left ventricular diastolic and systolic failure and that treatment with CPAP improves systolic function. SUMMARY: OSA should be considered in patients with systemic hypertension or heart failure.     

Obstructive sleep apnea and cardiovascular disease

Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension, arrhythmias, and atherosclerosis. Obesity is strongly linked to an increased risk of OSA, and weight loss can reduce the severity of OSA. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnea and the ensuing acute hemodynamic changes during sleep. Long-term CPAP treatment studies have shown a reduction in nocturnal cardiac ischemic episodes and improvements in daytime blood pressure levels and left ventricular function. Despite the availability of effective therapy, OSA remains an underdiagnosed and undertreated condition. A lack of physician awareness is one of the primary reasons for this deficit in diagnosis and treatment.     

Cardiovascular Implications in the Treatment of Obstructive Sleep Apnea

Epidemiological studies provide strong evidence that obstructive sleep apnea (OSA) is associated with cardiovascular complications such as systemic hypertension, congestive heart failure, and atrial fibrillation. Successful OSA treatment with continuous positive airway pressure (CPAP) has resulted in coincident reductions in systemic hypertension, improvements in left ventricular systolic function, and reductions in sympathetic nervous activity. These data suggest that successful treatment of OSA may reduce cardiovascular morbidity in such patients. Although CPAP is the more successful treatment for OSA when used properly and consistently, its clinical success is often limited by poor patient and partner acceptance, which leads to suboptimal compliance. Oral appliances or upper airway surgeries are considered a second line of treatment for patients with mild to moderate OSA who do not comply with or refuse long-term CPAP treatment. Oral devices such as mandibular repositioning appliances were recently shown to improve arterial hypertension in OSA patients. Electrical stimulation of the hypoglossal nerve is a new investigational therapy for patients with moderate to severe OSA. This new treatment option, if proven effective, may provide cardiovascular benefits secondary to treating OSA.     

Obstructive sleep apnea and hypertension

There has long been a recognized link between obstructive sleep apnea (OSA) and the cardiovascular system, no aspect of which has been more studied than blood pressure. Research in OSA has not only demonstrated dysregulation of homeostatic cardiovascular mechanisms but also has furthered our understanding of blood pressure regulatory control. Acute nocturnal blood pressure elevations associated with disordered breathing events have been reproduced from a number of observational studies, the accrual of which has also made an increasing argument for the importance of OSA in the pathogenesis of diurnal hypertension, as suggested by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), which implicated OSA as a secondary cause of hypertension. Accumulating data from randomized controlled treatment trials in OSA, particularly with continuous positive airway pressure, though sometimes inconsistent, suggest a potential role in blood pressure reduction. Further research is needed to better clarify indications for OSA treatment as well as its role as an adjunct to other antihypertensive treatments.     

Obstructive sleep apnea: an emerging risk factor for atherosclerosis

Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area.     

Acute cardiovascular diseases and respiratory sleep disorders.

Respiratory sleep disorders are a risk factor, sometimes independent, for acute cardiovascular diseases which are the most frequent cause of death among populations of industrialized countries. Snoring and obstructive sleep apnea (OSA) are generally involved, while the pathogenetic role of acute exacerbation of COPD seems less evident. The most important acute cardiovascular events related to sleep respiratory disorders are angina pectoris, acute myocardial infarction, cardiac arrhythmias (in some instances as paroxysmal attacks), systemic hypertension with hypertensive crisis, ischemic stroke. A respiratory sleep disorder should be suspected in all obese, cigarette smokers, alcoholics, hypertensives, who present symptoms of obstructive sleep apnea, where snoring may be a marker, and in patients with COPD. The diagnosis is readily established by performing polysomnography and, when needed, by 24-hour Holter monitoring and blood pressure ambulatory recording. Therapy aims at correcting risk factors with particular attention to weight reduction in obese patients. Furthermore, upper airway anatomic abnormalities should be eliminated. In obstructive sleep apnea, nasal continuous positive airway pressure during sleep is to be used, when necessary, while tracheostomy must be performed only in more severe cases.     

Obstructive sleep apnea and abnormal glucose metabolism

Obstructive sleep apnea (OSA) is a chronic disorder that is prevalent, especially in subjects with obesity or diabetes. OSA is related to several metabolic abnormalities, including diabetes, insulin resistance, hypertension, and cardiovascular diseases. Although Koreans are less obese than Caucasians, the prevalence of OSA is comparable in both groups. Thus, the impact of OSA on metabolism may be similar. Many epidemiologic and experimental studies have demonstrated that OSA is associated with glucose intolerance and insulin resistance via intermittent hypoxia, sleep fragmentation, and sleep deprivation. The effect of continuous positive airway pressure treatment on glucose metabolism is still controversial. Randomized controlled trials are needed to evaluate the ability of OSA treatment to reduce the risk of diabetes and insulin resistance in subjects without diabetes and to ameliorate glucose control in patients with diabetes.     

Baroreflex control of heart rate during sleep in severe obstructive sleep apnoea: effects of acute CPAP.

Baroreflex control of heart rate during sleep (baroreflex sensitivity; BRS) has been shown to be depressed in obstructive sleep apnoea (OSA), and improved after treatment with continuous positive airway pressure (CPAP). Whether CPAP also acutely affects BRS during sleep in uncomplicated severe OSA is still debatable. Blood pressure was monitored during nocturnal polysomnography in 18 patients at baseline and during first-time CPAP application. Spontaneous BRS was analysed by the sequence method, and estimated as the mean sequence slope. CPAP did not acutely affect mean blood pressure or heart rate but decreased cardiovascular variability during sleep. Mean BRS increased slightly during CPAP application (from 6.5+/-2.4 to 7.5+/-2.9 ms x mmHg(-1)), mostly in response to decreasing blood pressure. The change in BRS did not correlate with changes in arterial oxygen saturation or apnoea/hypopnoea index. The small change in baroreflex control of heart rate during sleep at first application of continuous positive airway pressure in severe obstructive sleep apnoea was unrelated to the acute resolution of nocturnal hypoxaemia, and might reflect autonomic adjustments to positive intrathoracic pressure, and/or improved sleep architecture. The small increase in baroreflex control of heart rate during sleep may be of clinical relevance as it was accompanied by reduced cardiovascular variability, which is acknowledged as an independent cardiovascular risk factor.     

Cardiovascular consequences of obstructive sleep apnea

Sleep apnea is associated with several cardiovascular disease conditions. A causal relationship between sleep apnea and each of these diseases is likely, but remains to be proven. The clearest evidence implicating OSA in the development of new cardiovascular disease involves data that show an increased prevalence of new hypertension in patients with OSA followed over 4 years [3]. Circumstantial evidence and data from small study samples suggest that OSA, in the setting of existing cardiovascular disease, may exacerbate symptoms and accelerate disease progression. The diagnosis of OSA always should be considered in patients with refractory heart failure, resistant hypertension, nocturnal cardiac ischemia, and nocturnal arrhythmias, especially in individuals with risk factors for sleep apnea (e.g., central obesity, age, and male gender). Treating sleep apnea may help to achieve better clinical control in these diseases and may improve long-term cardiovascular prognosis.     

Obstructive sleep apnea and its relationship to cardiac arrhythmias

Obstructive sleep apnea (OSA) affects approximately 4% of middle-aged men and 2% of middle-aged women. Cardiac arrhythmias are common problems in patients with OSA, even though the true prevalence and clinical relevance of cardiac arrhythmias remains to be determined. The presence and complexity of both tachyarrhythmias and bradyarrhythmias may influence morbidity, mortality, and the quality of life for OSA patients. Although the exact mechanisms underlying the link between OSA and cardiac arrhythmias are not well established, they could be partially the same proposed mechanisms relating OSA to different cardiovascular diseases. OSA is characterized by repetitive pharyngeal collapse during sleep that leads to markedly reduced or absent airflow, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against an occluded airway, and termination by arousal from sleep. These mechanisms elicit a variety of autonomic, hemodynamic, humoral, and neuroendocrine responses that by themselves evoke acute and chronic changes in cardiovascular function. These effects may lead to the development of cardiac arrhythmias and any other form of cardiovascular disease linked to OSA. The aims of this review are to describe the essential cardiovascular pathophysiological aspects of OSA, to outline the relationship between OSA and both tachyarrhythmias and bradyarrhythmias and their possible influence in the natural history of OSA patients, and to assess the effects of OSA treatment on the presence of cardiac arrhythmias.