Sleep Restriction and Augmented Vascular Risk in Prehypertension

描述（由申请人提供）：自愿睡眠限制很常见; 30%的美国成年人报告每晚睡眠<6小时，而那些睡眠不足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。睡眠剥夺可能是最常见的可预防的心血管危险因素之一。高血压前期也非常普遍，影响>25%的成年人，并且该人群处于特别高的发展风险中。 明显的高血压和心血管疾病。睡眠不足和高血压前期的共病可能非常常见，并与明显的高血压和心血管并发症有关。 没有明确的人类实验研究表明部分睡眠剥夺是否确实会导致心血管功能受损，也没有结论性的实验说明可能涉及的潜在生理和分子机制，特别是关于血压的任何变化。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个晚上的睡眠限制在每晚4小时。这些数据将与对照/正常睡眠序列进行比较。受试者将完成睡眠限制和对照序列，间隔3个月的洗脱期。因此，每个受试者都将作为他或她自己的对照，在一个与现实世界的睡眠限制非常接近的实验中。我们将联合收割机与最先进的睡眠监测系统相结合，以不引人注目的方式提供连续和准确的睡眠/清醒数据。我们目前正在成功进行的研究中使用这种睡眠限制模型，并且在进行心血管生理学的人类研究方面有几十年的经验。全面的系列生理数据将通过对睡眠限制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。在完成这些研究后，我们将能够确定：1。在整个24小时内睡眠限制对血压的影响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该应用的重要优势包括我们令人信服的初步数据，在最小化潜在混杂因素的同时实现特定目标的能力，我们对发展为高血压和心血管疾病的高风险群体的关注，将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制分子研究相结合，以及一个统计计划，将提供一个丰富的总结睡眠限制的影响，对四个具体目标。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措施的目标。 公共卫生相关性：我们建议检查9个晚上的适度睡眠限制是否会激活高血压前期患者的心血管疾病机制，从而可能增加高血压和心血管疾病的风险。这些发现将有助于解释普通人群睡眠时间的减少是否可能导致目前心血管疾病的流行，并提出降低这种风险的策略。

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. PUBLIC HEALTH RELEVANCE: We propose to examine whether 9 nights of modest sleep restriction results in activation of cardiovascular disease mechanisms in individuals with prehypertension, thus potentially increasing the risk of frank hypertension and cardiovascular disease. These findings will help explain whether the reduced sleep duration in the general population may be contributing to the current epidemic of cardiovascular disease, and suggest strategies to reduce this risk.