阻塞型睡眠呼吸暂停综合征与动脉粥样硬化

阻塞型睡眠呼吸暂停综合征（obstructive sleep apnea syndrome，OSAS）是临床上常见的重要慢性睡眠呼吸疾病。近年来的研究已证实，OSAS是动脉粥样硬化性疾病的独立危险因素。OSAS患者在睡眠时由于上气道阻塞或部分阻塞导致反复发作的慢性间歇性缺氧，这可能是其诱发动脉粥样硬化性疾病的重要原因，此过程中可能的分子机制包括：I-κB复合物和P38激酶激活调控NF-κB信号通路；端粒酶和Fas死亡配体依赖性细胞凋亡调控途径；间歇性缺氧诱发肝脏损伤导致高胆固醇血症和脂质过氧化反应代谢紊乱，引起不可逆的血管和周围组织重塑，伴有平滑肌增生和纤维化，导致动脉粥样硬化。     

Obstructive sleep apnea

Obstructive sleep apnea is an increasingly well-recognized disease characterized by periodic collapse of the upper airway during sleep. This leads to either complete or partial obstruction of the airway, resulting in apneas, hypopneas, or both. This disorder causes daytime somnolence, neurocognitive defects, and depression. It affects almost every system in the body, resulting in an increased incidence of hypertension, cardiovascular disease, stroke, pulmonary hypertension, cardiac arrhythmias, and altered immune function. It also increases the risk of having an accident, presumably as a result of associated somnolence. The gold standard for the diagnosis of sleep apnea is an overnight polysomnogram. Split-night studies are becoming increasingly common and allow for quicker implementation of therapy at a reduced cost. Treatment options for sleep apnea include weight loss, positional therapy, oral devices, continuous positive airway pressure (CPAP), and upper airway surgery. CPAP is the most efficacious and widely used therapy. Its complications include nasal congestion or dryness, mask discomfort, and claustrophobia. Heated humidifiers, newer types of masks, and nasal steroids have improved tolerance of this therapy. Bilevel positive-pressure therapy can be considered for patients who find it difficult to exhale against the consistently increased pressure of CPAP. The disease requires aggressive treatment to improve quality of life and prevent its complications.     

Obstructive sleep apnea syndrome (OSAS): Pathophysiology in Estonians

The aim of the study was to clarify the roles of age, obesity, smoking, alcohol, pathoanatomy and -physiology in Estonian's OSAS. For this 164 randomly chosen such patients were selected in different regions of Estonia. They underwent naso-oropharyngeal examination, physical examination of craniofacial abnormalities, and polysomnography. They also completed a self-reported questionnaire about smoking, alcohol use, excessive daytime sleepiness, hypertension, cardiac disorders, headaches, concentration disorders, and recurrent upper-airway diseases. The patients (129 men; 35 women) aged between 19 and 75 years (mean 47 ± 12), BMI between 21 and 49 (mean 30.5 ± 5.15), AHI between 5 and 105 (33 ± 22).The results showed that there was a high percentage of naso-oropharyngeal disorders, such as: recurrent upper-airway diseases (54.2%), nasal breathing disorders (63.5%), and hypertrophy of tonsils (57%). There was also a high percentage of general characteristics, such as alcohol use (64%), excessive daytime sleepiness (85.5%), overweight (63%), and hypertension (51.2%). The regression summary for the dependent variable AHI if p-level = 0.0042 (R = 0.63347013) included age, BMI, hypertension, cardiac disorders, headaches, nasal obstruction, hypertrophy of pharyngeal muscles, tongue level, submental fat and slow-wave sleep (S3 + S4%).In conclusion recurrent upper-airway diseases, nasal obstruction, and hypertrophy of tonsils in combination with smoking and alcohol caused the changes in the pharyngeal and lingual muscles. The latter gives rise to such sleep apnea-related problems as heart complaints, hypertension, headache and shortage of slow-wave sleep (SWS).     

Obstructive sleep apnea syndrome: differences between children and adults

The obstructive sleep apnea syndrome is a common cause of morbidity in childhood. The clinical presentation, pathophysiology, polysomnographic characteristics and treatment differ between children and adults. Measurements of the upper airway pressure-flow characteristics can be useful in evaluating upper airway function in patients with OSAS as well as the normal population.     

Obstructive sleep apnea syndrome. Effects of therapy on dyslipidemia

Summary Objective   Dyslipidemia is frequently observed in patients with obstructive sleep apnea syndrome (OSAS). The effects of OSAS treatment on lipid levels in these patients have been examined. Patients and Methods   95 consecutive patients (aged 56.6±9.5 years) with polysomnographically verified OSAS and LDL cholesterol levels of more than 130 mg per deciliter have been included in a prospective trial. Plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, apolipoprotein B, and lipoprotein (a) levels were determined in all patients at baseline and after long term therapy. Results   Total cholesterol (249.9 ± 31.4 vs. 240.0 ± 34.1 mg/dL; p = 0.01) and LDL cholesterol levels (179.4 ± 29.4 vs. 165.5 ± 32.5 mg/dL; p < 0.001) decreased significantly after 6 months in patients effectively treated, while they did not change significantly in those OSAS patients in whom treatment proved to be ineffective. Body mass index, HDL cholesterol, triglyceride, apolipoprotein B, and lipoprotein (a) levels did not change during follow-up. Both the change of total and LDL cholesterol levels were independently associated with treatment efficacy as indicated by the change of the apnea/hypopnea index. Conclusion   The results suggest that effective treatment of sleep-disordered breathing may have significant effects on the total and LDL cholesterol levels in OSAS patients.     

Obstructive sleep apnea in family members.

Two sons and their father had severe hypersomnolence and obstructive sleep apnea. A third son, although asymptomatic, was shown to have upper-airway obstruction during sleep. Electromyographic recordings of genioglossus activity in the two symptomatic sons revealed loss of tonic activity in early stages of sleep at times when sleep apnea occurred. The asymptomatic son showed loss of tonic activity during rapid-eye-movement sleep, the sleep period when upper-airway obstruction occurred. Two sudden deaths occurred in this family. A 30-year-old brother died at home while asleep, and a child of the asymptomatic brother died at the age of four months from presumed sudden-infant-death syndrome. Obstructive sleep apnea may have a familial basis; the tongue may be involved in the genesis of upper-airway obstruction during sleep.     

Obstructive sleep apnea: not just a sleep disorder

Obstructive sleep apnea (OSA) has long been recognized as a disorder characterized by snoring and frequent cessations of breathing resulting in fragmentation of sleep, which eventually leads to cumulative sleep debt in affected patients. Until two decades ago, snoring and apneas drew attention mainly as a social curiosity and sleep apnea was not thought of as a serious disorder with multisystem involvement. Impairment of quality of work and high incidence of motor vehicle accidents associated with OSA were recognized toward the end of the last century. Since the turn of this millennium physicians have become increasingly aware of the various cardiovascular complications, metabolic disturbances, and neuropsychologic deficits. It has become very clear in the last decade that patients with OSA have a high recurrence of atrial fibrillation after elective cardioversion if their sleep apnea is not treated with continuous positive airway pressure (CPAP). Poor control of diabetes mellitus and resistant hypertension in the setting of OSA has also been recognized and significant progress in our understanding in this area has been accomplished. Unless physicians include sleep in their system review, many cases will go undiagnosed, which will eventually result in cardiovascular complications. Patients are also not readily forthcoming with the symptoms of sleep apnea, as they often assume that symptoms, such as snoring and daytime sleepiness, are not something serious to be discussed with their physician. In this review, the characteristics, the pathophysiology, and epidemiology of OSA are discussed. Furthermore, the mechanisms by which OSA affects the cardiovascular, endocrine, and metabolic functions have been explored.     

Obstructive sleep apnea syndrome in siblings: an 8-year Swedish follow-up study

BACKGROUND: Understanding the genetic transmission of obstructive sleep apnea syndrome (OSAS) will help clinicians identify patients at risk and offer opportunities for intervention and treatment at specialist clinics. OBJECTIVE: To estimate familial risk of hospitalization for OSAS in the adult population of Sweden, and to determine if there are any differences by age and sex. DESIGN, SETTING, AND PARTICIPANTS: Using the MigMed database at the Karolinska Institute, we divided the population of Sweden into sibling groups based on a shared mother and father and ascertained the presence or absence of a primary hospital diagnosis of OSAS in each individual during the follow-up period, 1997 to 2004. Individuals were categorized as having or not having a sibling with OSAS, based on the presence or absence of the disorder in at least 1 of their siblings. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated for men and women with a sibling with OSAS, compared with men and women in the reference group (SIR = 1). RESULTS: After accounting for socioeconomic status, age, geographic region, and period of diagnosis, men with at least 1 sibling who had OSAS had a SIR of 3.42 (95% CI, 2.18-5.36); the corresponding SIR in women was 3.25 (95% CI, 1.84-5.65). CONCLUSIONS: Our results indicate that physicians should consider family history of OSAS when deciding whether to refer a patient for further sleep examinations.     

Obstructive sleep apnea syndrome: evaluation of subcritical continuous positive airway pressure

Twenty eight of 48 patients diagnosed of obstructive sleep apnea syndrome over a six month duration opted for CPAP therapy. Half of them were given critical CPAP (Group A) and other half were prescribed subcritical level of CPAP (Group B). Re-evaluation after 3 months revealed that side effects like headache and feeling of inconvenience were more in Group A, though beneficial effects were same in both groups. It is concluded that subcritical level of CPAP should be adopted to treat patients of obstructive sleep apnea syndrome.     

Obstructive sleep apnea and carotid-artery intima-media thickness

STUDY OBJECTIVES: We investigated whether the carotid-artery intimamedia thickness (IMT) measured by ultrasonography, which is regarded as an indicator of atherosclerosis, was associated with the severity of obstructive sleep apnea (OSA). DESIGN: Cross-sectional study. SETTING: A sleep laboratory in a general hospital in Japan. PATIENTS: A total of 167 patients referred to the sleep laboratory of our hospital for screening or treatment of OSA were investigated. They had no history of chronic obstructive pulmonary disease, cerebrovascular disease, or cardiovascular disease. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Obstructive sleep apnea was diagnosed by polysomnography. Carotid-artery IMT was measured by ultrasonography, and known risk factors for atherosclerosis (age, obesity, hyperlipidemia, hypertension, diabetes mellitus, and insulin resistance) were also investigated. Multiple regression analysis was performed to assess the association between IMT and the severity of OSA, after adjusting for confounding factors. This analysis revealed that the apnea-hypopnea index, the duration of an oxygen saturation below 90%, and the mean nadir oxygen saturation were significantly associated with the IMT after adjustment for confounding factors that could promote atherosclerosis. Moreover, OSA-related hypoxemia was associated with the IMT independently of the apnea-hypopnea index. CONCLUSIONS: Our results demonstrated that the severity of OSA is independently related to atherosclerosis and that the severity of OSA-related hypoxemia is more important than the frequency of obstructive events.     

Obstructive sleep apnea syndrome caused by uncommon tumors of the upper aerodigestive tract

Obstructive sleep apnea syndrome (OSAS) is always caused by anatomic abnormalities, including nasal cavity, pharynx, and neuromuscular dysfunctions, leading to airway narrowing. OSAS associated with a mass in the aerodigestive tract is rare. In the present study, we report OSAS caused by 9 cases of preoperative uncommon tumors in the aerodigestive tract. Two tumors in the parapharyngeal space were pleomorphic adenoma, one oropharyngeal tumor was mucoepidermoid carcinoma, one tumor in the right tonsil was schwannoma, and five tumors were non-Hodgkin’s lymphoma (NHL). Of the five NHL cases, one in the nasopharynx was diffuse large B-cell lymphoma, two were mantle cell lymphoma, one was chronic lymphocytic leukemia/small lymphocytic lymphoma, and one was NHL. Tumors in the aerodigestive tract should be considered in the differential diagnosis of OSAS upon exacerbation of snoring or sudden gasping. Further examinations should be performed, including a routine workup (computed tomography (CT) and magnetic resonance imaging) and positron emission tomography/CT.     

Obstructive sleep apnea,immuno-inflammation,and atherosclerosis

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia–reoxygenation. This IH induces several consequences such as hemodynamic, hormonometabolic, oxidative, and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors and is related to the severity of nocturnal hypoxia. Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. Impaired vasoreactivity with endothelial dysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin, and renin–angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. Oxidative stress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease.