Sleep Restriction and Augmented Vascular Risk in Prehypertension

描述(申请人提供)：自愿睡眠限制很常见；30%的美国成年人报告每晚睡眠时间为6小时，而那些这样做的人患心血管疾病的可能性要高出24%，患高血压的风险要高出一倍。睡眠不足可能是最常见的可预防的心血管风险因素之一。高血压前期也非常普遍，影响了25%的成年人，这一人群罹患高血压的风险特别高。 弗兰克高血压和心血管疾病。睡眠不足和高血压前期的并存很可能是非常常见的，这可能会导致坦率的高血压和心血管并发症。目前还没有明确的人类实验研究表明，部分睡眠剥夺是否真的会导致心血管功能受损，也没有确凿的实验研究可能涉及的潜在生理和分子机制，特别是与血压变化有关的机制。我们建议在高血压前期患者中进行一项随机交叉研究，包括3天的适应期，9个晚上的睡眠时间限制为每晚4个小时。这些数据将与控制/正常睡眠序列进行比较。受试者将完成睡眠限制和控制序列，间隔3个月的洗涤期。因此，每个受试者都将在与现实世界睡眠限制非常接近的实验中充当自己的对照。我们将把这个强大的模型与最先进的睡眠监测系统结合起来，以一种不引人注目的方式提供连续、准确的睡眠/唤醒数据。我们目前正在成功地正在进行的研究中使用这种睡眠限制模式，并在进行心血管生理学的人体研究方面拥有数十年的经验。全面的系列生理学数据将通过对睡眠受限前后组织活检获得的微血管和脂肪细胞的详细翻译分子研究来补充。这些研究完成后，我们将能够确定：1.睡眠限制对整个24小时内血压的影响2.睡眠限制对神经循环控制的影响3.睡眠限制对血管功能的影响4.SLEP限制对全身和脂肪组织炎症的影响这一应用的重要优势包括我们令人信服的初步数据，在将潜在混杂因素降至最低的同时实现特定目标的能力，我们关注的是患有明显高血压和心血管疾病的高危人群，广泛接受的心血管风险替代物与血管内皮细胞和脂肪细胞水平的机械性分子研究的整合，以及一个统计计划，它将提供关于睡眠限制对四个具体目标的影响的丰富总结。我们的长期目标是确定将睡眠限制与心血管疾病联系起来的基本生物学机制，从而确定旨在降低心血管风险的干预目标。

DESCRIPTION (provided by applicant): Voluntary sleep restriction is common; 30% of the US adult population reports <6 h of sleep per night, and those who do are 24% more likely to have cardiovascular disease and have twice the risk of hypertension. Sleep deprivation may be one of the commonest preventable cardiovascular risk factors. Prehypertension is also highly prevalent, affecting >25% of adults, and this population is at particularly high risk of developing frank hypertension and cardiovascular disease. The comorbidity of inadequate sleep and prehypertension is likely to be very common, with implications for frank hypertension and cardiovascular complications. No definitive experimental studies in humans show whether partial sleep deprivation indeed results in impaired cardiovascular function, nor are there conclusive experiments addressing the underlying physiologic and molecular mechanisms that may be involved, especially with regard to any changes in blood pressure. We propose to conduct a randomized, cross-over study in individuals with prehypertension, incorporating a 3-day acclimation period with 9 nights of sleep restricted to 4 hours per night. These data will be compared to a control/normal sleep sequence. Subjects will complete both sleep restriction and control sequences, separated by a 3-month washout period. Thus, each subject will serve as his or her own control in an experiment that closely matches real-world sleep restriction. We will combine this robust model with a state-of-the-art sleep monitoring system that provides continuous and accurate sleep/wake data in an unobtrusive way. We are currently using this model of sleep restriction in successful ongoing studies and have several decades of experience in conducting human studies of cardiovascular physiology. Comprehensive serial physiologic data will be complemented by detailed translational molecular studies of microvessels and adipocytes obtained by tissue biopsy before and after sleep restriction. Upon completion of these studies we will be able to ascertain: 1. The effects of sleep restriction on blood pressure throughout the entire 24-hour period 2. The effects of sleep restriction on neural circulatory control 3. The effects of sleep restriction on vascular function 4. The effects of slep restriction on systemic and adipose tissue inflammation Important strengths of this application include our compelling preliminary data, the ability to accomplish the specific aims while minimizing potential confounders, our focus on a group at high risk of developing frank hypertension and cardiovascular disease, the integration of widely accepted surrogates of cardiovascular risk with mechanistic molecular studies at the level of the vascular endothelial cell and the adipocyte, and a statistical plan that will provide a rich summary of the effects of sleep restriction on the four specific aims. Our long-term goal is to identify the fundamental biologic mechanisms that link sleep restriction to cardiovascular disease so as to define targets for interventions directed at reducing cardiovascular risk.