Influences of sleep apnea on the progression of atherosclerosis, metabolic syndrome, and vascular diseases : inhibitory roles of CPAP on the prevention of vascular diseases

阻塞性睡眠呼吸暂停综合征（OSAS）最近被认为是心血管疾病和代谢综合征的危险因素。OSAS与肥胖、胰岛素抵抗和糖尿病有关。此外，OSAS患者的瘦素和胰岛素水平升高与肥胖无关，内脏脂肪是与睡眠呼吸暂停相关的主要参数。OSAS与胰岛素抵抗和2型糖尿病的关联已被证实。脂联素是一种由脂肪细胞分泌的激素，作为抗糖尿病和抗动脉粥样硬化的脂肪细胞因子。在肥胖、胰岛素抵抗和2型糖尿病的情况下，血液中的脂联素水平会降低。我们发现OSAS患者的血浆脂联素水平比没有OSAS的肥胖对照组降低。脂联素水平与OSAS严重程度相关，如呼吸暂停低通气指数（AHI）所示，而不是体重指数所示的肥胖指数。低脂、高连接素水平也与hsCRP和IL-6水平升高有关。从炎症角度来看，睡眠呼吸暂停患者的TNF-、IL-6、hsCRP、粘附分子和单核细胞化学引诱蛋白-1的水平明显高于正常对照组89根据AHI， IL-6和hsCRP水平与OSAS严重程度独立相关。此外，hsCRP水平与内脏脂肪组织相关，并与胰岛素抵抗综合征的组成部分显著相关。这些数据支持了炎症过程和代谢综合征在OSAS患者的动脉粥样硬化病变中被激活的观点。c反应蛋白和其他炎症细胞因子加速OSAS患者动脉粥样硬化的进展。此外，阻塞性睡眠呼吸暂停患者循环中腺苷和尿尿酸水平的升高与活性氧的产生增加有关。氧化还原敏感基因表达的激活可能是由于这些基因的一些蛋白产物，包括血管内皮生长因子、促红细胞生成素、内皮素-1、炎症细胞因子和粘附分子的增加。这些结果提示氧化还原敏感转录因子如缺氧诱导因子-1、激活蛋白-1和核因子- b参与了这一过程。重要的是，高水平的致动脉粥样硬化炎症介质通过osas特异性治疗（如鼻持续气道正压）得到改善。因此，OSAS在代谢综合征和全身性炎症性疾病中起着至关重要的作用。此外，阻塞性睡眠呼吸暂停引起的缺氧应激增加了未经治疗的OSAS患者循环肾上腺髓质素（ADM）水平。长期CPAP治疗可降低患者动脉血氧去饱和程度和血浆ADM水平。长期氧疗还可降低OSAS- Less患者夜间低氧血症和血浆肾上腺髓质素水平

Obstructive sleep apnea syndrome (OSAS) is recently recognized as a risk factor for cardiovascular disorders and metabolic syndrome. OSAS is related to obesity, insulin resistance, and diabetes mellitus. In addition, leptin and insulin levels were elevated in patients with OSAS independently of obesity, and visceral fat was the primary parameter linked with sleep apnea. The association of OSAS with insulin resistance and diabetes type 2 has been confirmed. Adiponectin is a hormone secreted by adipocytes that acts as an antidiabetic and antiatherogenic adipocytokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance, and type 2 diabetes. We have found that plasma level of adiponectin is decreased in OSAS patients compared with that in obese control subjects without OSAS. The level of adiponectin is associated with the severity of OSAS as indicated by apnea-hypopnea index (AHI), rather than obesity indexed as body mass index. The lower adipo … More nectin level is also associated with increased levels of hsCRP and IL-6.At the inflammatory point of view, the levels of TNF-, IL-6, hsCRP, adhesion molecules, and monocyte chemoattractant protein-1 were markedly and significantly elevated in patients with sleep apnea than those in normal control subjects.89 IL-6 and hsCRP levels were independently associated with OSAS severity as indicated by the AHI. In addition, hsCRP level is associated with visceral adipose tissue and is significantly associated with the components of insulin resistance syndrome. These data support the belief that inflammatory processes and metabolic syndrome are activated in atherosclerotic lesions in patients with OSAS. C-reactive protein and other inflammatory cytokines accelerate the progression of atherosclerosis in patients with OSAS. In addition, increase in circulating levels of adenosine and urinary uric acid in patients with obstructive sleep apnea are implicated with increased production of reactive oxygen species. Activation of redox-sensitive gene expression is suggested by the increase in some protein products of these genes, including vascular endothelial growth factor, erythropoietin, endothelin-1, inflammatory cytokines, and adhesion molecules. These results implicate the participation of redox-sensitive transcription factors as hypoxia-inducible factor-1, activator protein-1 and nuclear factor-B.Importantly, the elevated levels of atherogenic inflammatory mediators were improved by the OSAS-specific treatment such as nasal continuous positive airway pressure. Thus, OSAS plays a crucial role in metabolic syndrome and systemic inflammatory disorders. Furthermore, the hypoxic stress caused by obstructive sleep apnea increased circulating adrenomedullin (ADM) levels in untreated OSAS. The long-term CPAP decreased both the magnitude of arterial oxygen desaturation and plasma ADM levels in the patients. The long-term oxygen therapy also reduced OSAS-induced nocturnal hypoxemia and plasma adrenomedullin levels in patients with OSAS Less