SDB, metabolic syndrome, and vascular function

描述（由申请人提供）： 胰岛素抵抗和代谢综合征与血管内皮功能障碍和动脉粥样硬化有共同的危险因素和发病机制。睡眠呼吸障碍（SDB）可能以复杂和错综复杂的方式与这种致病环境相关，既作为结果（通过肥胖），也作为原因（通过低氧血症，氧化应激和交感神经超负荷）。本提案的主要目的是在威斯康星州睡眠队列（WSC）研究中研究SDB与代谢综合征和血管功能障碍发生率之间的纵向相关性，该研究是一项基于社区的中年个体样本，在过去15年中重复进行了完整的多导睡眠图研究，每位参与者最多4次，间隔4年。这些个体的其他现有数据包括睡眠习惯、重复血压测量（包括坐位和动态血压）、人体测量数据、空腹血清葡萄糖、胰岛素、瘦素、生长激素释放肽、炎症标志物、ApoE-E4和亚临床动脉粥样硬化的非侵入性标志物（踝臂指数）。总共600名在WSC中至少接受过2次访视的参与者将被招募到研究中，包括a）约150例偶发代谢综合征病例，和B）约450-470名队列成员的随机样本。这些参与者将在不同血管床中接受血管功能的非侵入性测量，包括：（1）肱动脉反应性;（2）脑动脉对高碳酸血症的反应性;和（3）视网膜小动脉/小静脉比率。此外，我们将通过测量缺氧应激（VEGF）、氧化应激（尿异前列腺素）以及交感神经和下丘脑-垂体-肾上腺轴功能（心率变异性、尿去甲肾上腺素、尿皮质醇）的标志物来评估可能的介导机制。拟定研究将以足够的统计把握度检验以下假设：近期或既往SDB（通过AHI、低氧血症指数评估）可预测偶发代谢综合征，并与胰岛素抵抗程度（HOMA-IR）和血管或内皮功能障碍相关，同时控制潜在混杂因素或解释变量，包括现有和新获得的协变量信息。

DESCRIPTION (provided by applicant): Insulin resistance and the metabolic syndrome share risk factors and pathogenetic mechanisms with vascular endothelial dysfunction and atherosclerosis. Sleep disorder breathing (SDB) might be associated with this pathogenetic milieu in complex and intricate ways, both as a consequence (via obesity) and as a cause (via hypoxemia, oxidative stress, and sympathetic overload). The primary objective of this proposal is to study the longitudinal association between SDB and the incidence of the metabolic syndrome and vascular dysfunction in a nested case-cohort sample of participants in the Wisconsin Sleep Cohort (WSC) Study, a community-based sample of middle-age individuals who have undergone repeated full polysomnography studies over the last 15 years, up to four in each participants, four years apart. Additional existing data on these individuals include extensive data on sleep habits, repeat blood pressure measurements (including both sitting and ambulatory blood pressure), anthropometric data, measures of fasting serum glucose, insulin, leptin, ghrelin, inflammatory markers, ApoE-E4, and non-invasive markers of subclinical atherosclerosis (ankle-arm index). A total of 600 participants who have had at least 2 visit in the WSC will be recruited into the study, including a) about 150 cases of incident metabolic syndrome, and b) a random sample of about 450-470 members of the cohort. These participants will undergo non-invasive measures of vascular function in different vascular beds, including: (1) brachial artery reactivity; (2) cerebral artery responsiveness to hypercapnia; and (3) retinal arteriolar/venular ratio. In addition, we will assess possible mediating mechanisms by measuring markers of hypoxic stress (VEGF), oxidative stress (urinary isoprostane), and markers of sympathetic and hypothalamic-pituitary-adrenal axis function (heart rate variability, urinary norepinephrine, urinary cortisol). The proposed study will test, with adequate statistical power, the hypothesis that recent or past SDB (assessed by AHI, hypoxemia index) predict incident metabolic syndrome and is related to the degree of insulin resistance (HOMA-IR), and vascular or endothelial dysfunction while controlling for potential confounders or explanatory variables, including the existing and newly acquired covariate information.