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.     

Cardiovascular biomarkers in clinical practice of sleep apnea

Obstructive sleep apnea syndrome (OSAS) leads to cardiovascular complications such as coronary artery disease, left/right ventricular hypertrophy and dysfunction, heart failure, systemic and pulmonary hypertension, arrhythmias and stroke; and these all cardiovascular complications increase morbidity and mortality of OSAS. However, Cheyne-Stokes respiration, central and obstructive apneas may occur in the patient with heart failure. Increased sympathetic activity by hypoxemia and endothelial dysfunction play a role in cardiovascular complications. Some cardiovascular biomarkers have a role in early diagnosis, treatment and prognosis. In the present review, some cardiovascular biomarkers such as serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukins, adiponectin, heart-type fatty acid binding protein (hFABP) and brain (B-type) natriuretic peptide (BNP), and their clinical importance were reviewed.     

Cardiovascular disorders and obstructive sleep apnea syndrome

The first polysomnographic recordings with concomitant monitoring of cardiocirculatory parameters demonstrated that obstructive apneas arising during sleep are accompanied by a marked increase in pulmonary and systemic arterial pressure and severe alveolar hypoventilation. Apneas also may give rise to cardiac arrhythmias, namely potentially life-threatening bradyarrhythmias. The long-term repercussions of these nocturnal cardiocirculatory changes on subsequent cardiovascular diseases and the patient's life expectancy are more controversial. There is little doubt that patients with obstructive sleep apnea syndrome (OSAS) have systemic arterial hypertension, ischemic heart disease, transient ischemic attacks, or stroke more often than control populations and have a shorter life expectancy. However, these clinical manifestations may be at least partly due to myriad other risk factors almost always present in OSAS patients (in particular obesity, diabetes, alcoholism, and cigarette smoking). Few multivariate epidemiological surveys have addressed all these confounding factors. The effectiveness of continuous positive airway pressure treatment in reducing the incidence of cardiovascular comorbidity in OSAS patients is not disputed, even though controlled epidemiological surveys on large populations are scant. This overview of cardiovascular disorders and OSAS examines the latest literature findings aimed at establishing the true impact of nocturnal apneas on cardiocirculatory disease (systemic arterial hypertension, ischemic heart disease, stroke, pulmonary hypertension and right heart failure and mortality).     

Cardiovascular Disorders and Obstructive Sleep Apnea Syndrome

The first polysomnographic recordings with concomitant monitoring of cardiocirculatory parameters demonstrated that obstructive apneas arising during sleep are accompanied by a marked increase in pulmonary and systemic arterial pressure and severe alveolar hypoventilation. Apneas also may give rise to cardiac arrhythmias, namely potentially life-threatening bradyarrhythmias. The long-term repercussions of these nocturnal cardiocirculatory changes on subsequent cardiovascular diseases and the patient's life expectancy are more controversial. There is little doubt that patients with obstructive sleep apnea syndrome (OSAS) have systemic arterial hypertension, ischemic heart disease, transient ischemic attacks, or stroke more often than control populations and have a shorter life expectancy. However, these clinical manifestations may be at least partly due to myriad other risk factors almost always present in OSAS patients (in particular obesity, diabetes, alcoholism, and cigarette smoking). Few multivariate epidemiological surveys have addressed all these confounding factors. The effectiveness of continuous positive airway pressure treatment in reducing the incidence of cardiovascular comorbidity in OSAS patients is not disputed, even though controlled epidemiological surveys on large populations are scant. This overview of cardiovascular disorders and OSAS examines the latest literature findings aimed at establishing the true impact of nocturnal apneas on cardiocirculatory disease (systemic arterial hypertension, ischemic heart disease, stroke, pulmonary hypertension and right heart failure and mortality).     

Sleep apnea and cardiovascular risk

Sleep apnea is evident in approximately 10% of adults in the general population, but in certain cardiovascular diseases, and in particular those characterized by sodium and water retention, its prevalence can exceed 50%. Although sleep apnea is not as yet integrated into formal cardiovascular risk assessment algorithms, there is increasing awareness of its importance in the causation or promotion of hypertension, coronary artery disease, heart failure, atrial arrhythmias, and stroke, and thus, not surprisingly, as a predictor of premature cardiovascular death.Sleep apnea manifests as two principal phenotypes, both characterized by respiratory instability: obstructive (OSA), which arises when sleep-related withdrawal of respiratory drive to the upper airway dilator muscles is superimposed upon a narrow and highly compliant airway predisposed to collapse, and central (CSA), which occurs when the partial pressure of arterial carbon dioxide falls below the apnea threshold, resulting in withdrawal of central drive to respiratory muscles.The present objectives are to: (1) review the epidemiology and patho-physiology of OSA and CSA, with particular emphasis on the role of renal sodium retention in initiating and promoting these processes, and on population studies that reveal the long-term consequences of untreated OSA and CSA; (2) illustrate mechanical, autonomic, chemical, and inflammatory mechanisms by which OSA and CSA can increase cardiovascular risk and event rates by initiating or promoting hypertension, atherosclerosis, coronary artery disease, heart failure, arrhythmias, and stroke; (3) highlight insights from randomized trials in which treating sleep apnea was the specific target of therapy; (4) emphasize the present lack of evidence that treating sleep apnea reduces cardiovascular risk and the current clinical equipoise concerning treatment of asymptomatic patients with sleep apnea; and (5) consider clinical implications and future directions of clinical research and practice.     

阻塞性睡眠呼吸暂停低通气综合征与心律失常

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是一种睡眠过程中反复出现的以呼吸暂停、睡眠结构紊乱及低氧血症等为特征的疾病.大量的临床研究证明0SAHS与高血压、代谢综合征、冠心病、心力衰竭、脑卒中以及心律失常等疾病密切相关,现通过系统综述,探讨分析了OSAHS与多种心律失常发生的关系,归纳总结其发生机制及心电学特点,并对OSAHS及其合并症的治疗进展进行相关讨论.     

Obstructive sleep apnea presenting with nocturnal angina, heart failure, and near-miss sudden death

An obese woman with a one-year history of episodic nocturnal chest pain was admitted because of shock and pulmonary edema. A clinical diagnosis of acute myocardial infarction and cardiogenic shock was made. She was ventilated and successfully resuscitated. Subsequent investigations showed no evidence of cardiac dysfunction or coronary disease, but sleep study confirmed the diagnosis of obstructive sleep apnea syndrome (OSAS). We suggest that the nocturnal angina and heart failure in this patient might have resulted from extreme hypoxemia produced by OSAS. This case raised the possibility that the high cardiovascular mortality rate reported in OSAS might not necessarily relate to underlying coronary artery disease. Further investigations are required to delineate the true incidence of coronary disease in patients with OSAS.     

Obstructive Sleep Apnoea: From pathogenesis to treatment: Current controversies and future directions

Obstructive sleep apnoea (OSA) is a common disease, recognized as an independent risk factor for a range of clinical conditions, such as hypertension, stroke, depression and diabetes. Despite extensive research over the past two decades, the mechanistic links between OSA and other associated clinical conditions, including metabolic disorders and cardiovascular disease, remain unclear. Indeed, the pathogenesis of OSA itself remains incompletely understood. This review provides opinions from a number of leading experts on issues related to OSA and its pathogenesis, interaction with anaesthesia, metabolic consequences and comorbidities, cardiovascular disease, genetics, measurement and diagnosis, surgical treatment and pharmacotherapeutic targets.     

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.     

Obstructive sleep apnea syndrome is a systemic disease. Current evidence

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. This disease has many potential consequences including excessive daytime sleepiness, neurocognitive deterioration, endocrinologic and metabolic effects, and decreased quality of life. Metabolic syndrome is another highly prevalence emerging public health problem that represents a constellation of cardiovascular risk factors. Each single component of the cluster increases the cardiovascular risk, but the combination of factors is much more significant. It has been suggested that the presence of OSAS may increase the risk of developing some metabolic syndrome features. Moreover, OSAS patients are at an increased risk for vascular events, which represent the greatest morbidity and mortality of all associated complications. Although the etiology of OSAS is uncertain, intense local and systemic inflammation is present. A variety of phenomena are implicated in this disease such as modifications in the autonomic nervous system, hypoxemia-reoxygenation cycles, inflammation, and coagulation-fibrinolysis imbalance. OSAS patients also present increased levels of certain biomarkers linked to endocrine-metabolic and cardiovascular alterations among other systemic consequences. All of this indicates that, more than a local abnormality, OSAS should be considered a systemic disease.     

Should visceral fat, strictly linked to hepatic steatosis, be depleted to improve survival?

Numerous epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and its further expression, i.e., nonalcoholic fatty liver disease and death. Using novel models of visceral obesity, several studies have demonstrated that the relationship between visceral fat and longevity is causal, while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. The need of reducing the visceral fat to improve survival, mainly taking into account the strict link between nonalcoholic fatty liver disease and the coronary artery disease is discussed.     

Cardiovascular diseases in obstructive sleep apnea

Obstructive sleep apnea (OSA) affects approximately 5% of women and 15% of men in the middle-aged adults, and associated with adverse health outcomes. Cardiovascular disturbances are the most serious complications of OSA. These complications include heart failure, left/right ventricular dysfunction, acute myocardial infarction, arrhythmias, stroke, systemic and pulmonary hypertension. All these cardiovascular complications increase morbidity and mortality of OSA. Several epidemiologic studies have demonstrated that sleep related breathing disorders are an independent risk factor for hypertension, probably resulting from a combination of intermittent hypoxia and hypercapnia, arousals, increased sympathetic activity, and altered baroreflex control during sleep. Arterial hypertension, obesity, diabetes mellitus and coronary artery disease (CAD) which are independent predictors of left ventricular dysfunction, often have co-existence with OSA. Especially severe OSA patients having diastolic dysfunction might have an increased risk of heart failure, since diastolic dysfunction might be combined with systolic dysfunction. Early recognition and appropriate therapy of ventricular dysfunction is advisable to prevent further progression to heart failure and death. Patients with acute myocardial infarction, especially if they had apneas and hypoxemia without evident heart failure should be evaluated for sleep disorders. So, patients with CAD should be evaluated for OSA and vice versa. Early recognition and treatment of OSA may improve cardiovascular functions. Continuous positive airway pressure (CPAP) applied by nasal mask, is still the gold standard method for treatment of the disease and prevention of complications.     

Obstruktive Schlafapnoe und kardiovaskuläre Komorbidität

Obstructive sleep apnea (OSA) is the most common entity of sleep-disordered breathing in Germany. OSA is independently associated with an increased risk of cardiovascular disease. It predisposes to arterial hypertension in particular, but also to coronary artery disease, cardiac arrhythmias and atrial fibrillation. OSA has been established as an independent risk factor for arterial hypertension, and treatment of OSA with continuous positive airway pressure (CPAP) causes a significant and persistent drop in blood pressure. Long-term CPAP treatment reduces the rate of important cardiovascular comorbidities.     

Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome.

Cardiovascular disorders are common in patients with obstructive sleep apnoea syndrome (OSAS) but there is debate as to whether OSAS is an independent risk factor for their development, since OSAS may be associated with other disorders and risk factors that predispose to cardiovascular disease. In an effort to quantify the risk of OSAS patients for cardiovascular disease arising from these other factors, the authors assessed the future risk for cardiovascular disease among a group of 114 consecutive patients with established OSAS prior to nasal continuous positive airway pressure therapy, using an established method of risk prediction employed in the Framingham studies. Patients were 100 males, aged (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90 diastolic, 68% of patients were hypertensive. Only 18% were current smokers, while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%, 95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95% CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%; 95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive sleep apnoea syndrome patients are at high risk of future cardiovascular disease from factors other than obstructive sleep apnoea syndrome, and may help explain the difficulties in identifying a potential independent risk from obstructive sleep apnoea syndrome.     

OSAHS与冠状动脉粥样硬化性心脏病的研究进展

阻塞性睡眠呼吸暂停低通气综合征(OSAHS)由于睡眠时气道塌陷而引起反复缺氧、白天嗜睡等症状,且与高血压、心律失常、冠状动脉粥样硬化性心脏病(CHD)和心力衰竭等心血管疾病关系密切。OSAHS在促进心血管疾病发生、发展过程中起到重要作用,目前OSAHS作为CHD的重要危险因素逐渐受到重视。本文就OSAHS引起CHD的发病机制,OSAHS与冠状动脉狭窄程度之间的联系,OSAHS合并CHD的不良预后及持续气道正压通气对该类患者预后的影响作一综述。     

Inflammation accelerates atherosclerotic processes in obstructive sleep apnea syndrome (OSAS)

Obstructive sleep apnea syndrome (OSAS) is an often underestimated sleep disorder that has been associated with cardiovascular disease. OSAS is characterized by cycles of apnea and/or hypopnea during sleep caused by the collapse of the upper airways. Intermittent hypoxia deriving from the cycles of apnea/arousals (to retrieve the ventilation) plays a pivotal role in the pathogenesis of the disease. Obesity is the most frequent predisposing condition of OSAS. Recent evidence suggests that OSAS could be considered as a pro-atherosclerotic disease, independently of visceral fat amount. Oxidative stress, cardiovascular inflammation, endothelial dysfunction, and metabolic abnormalities in OSAS could accelerate atherogenesis. The present review is focused on the possible pathophysiological mediators which could favor atherosclerosis in OSAS.     

Sleep apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.

Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death. The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. The present report, which arose out of a European Union Cooperation in the field of Scientific and Technical Research (COST) action on OSAS (COST B26), reviews the current evidence for an independent association and proposes research priorities to identify the underlying mechanisms involved, with a view to identifying novel therapeutic strategies. Large-scale collaborative studies of carefully defined patient populations with obstructive sleep apnoea syndrome, adequately controlled for potential confounders, are needed. Such studies carry the prospect of evaluating potential interactions between different basic mechanisms operating in obstructive sleep apnoea syndrome and cardiovascular disease, and interactions with other related disorders, such as obesity, diabetes and dyslipidaemia. Furthermore, translational studies involving cell culture and animal models linked to studies of obstructive sleep apnoea syndrome patients are necessary to integrate basic mechanisms with the clinical disorder.     

OSA: the new cardiovascular disease Part II: overview of cardiovascular diseases associated with obstructive sleep apnea

Obstructive sleep apnea (OSA), present in 5–15% of adults, is strongly associated with the incidence and poor outcome of hypertension, coronary artery disease, arrhythmia, heart failure, and stroke. Treatment of OSA completely reverses its cardiovascular consequences. In this review, we discuss the clinical evidence for the strong association between OSA and cardiovascular disease and present an argument for approaching OSA as a cardiovascular disease. We particularly focus on the causative relationship between OSA and hypertension, and on the increasingly recognized relationship between OSA and heart failure.     

Obstructive sleep apnea syndrome

Obstructive sleep apnea (OSA) syndrome is a common but often unrecognized disorder caused by pharyngeal collapse during sleep and characterized by frequent awakenings, disrupted sleep and consequent excessive daytime sleepiness. With the increasing epidemic of obesity, the most important risk factor for OSA, prevalence of the disease will increase over the coming years thus representing an important public-health problem. In fact, it is now recognized that there is an association between OSA and hypertension, metabolic syndrome, diabetes, heart failure, coronary artery disease, arrhythmias, stroke, pulmonary hypertension, neurocognitive and mood disorders. Diagnosis is based on the combined evaluation of clinical manifestations and objective sleep study findings. Cardinal symptoms include snoring, sleepiness and significant reports of sleep apnea episodes. Polysomnography represents the gold standard to confirm the clinical suspicion of OSA syndrome, to assess its severity and to guide therapeutic choices. Behavioral, medical and surgical options are available for the treatment. Continuous positive airway pressure (CPAP) represents the treatment of choice in most patients. CPAP has been demonstrated to be effective in reducing symptoms, cardiovascular morbidity and mortality and neurocognitive sequelae, but it is often poorly tolerated. The results of clinical studies do not support surgery and pharmacological therapy as first-line treatment, but these approaches might be useful in selected patients. A better understanding of mechanisms underlying the disease could improve therapeutic strategies and reduce the social impact of OSA syndrome.     

大动脉炎加速冠状动脉粥样硬化机制的研究进展

大动脉炎是一种慢性、非特异性、肉芽肿性血管炎,先前研究认为其参与冠状动脉狭窄的主要机制是主动脉炎症扩展至冠状动脉,导致内膜增生及中外膜纤维化挛缩.近年来,大量研究发现大动脉炎患者的冠状动脉粥样硬化程度及心血管疾病发生率明显升高,且传统的心血管危险因素(高脂血症、高血压、糖尿病、吸烟和衰老等)并不能完全解释心血管疾病风险...