Sleep and Circadian Mechanisms Contributing to Disparity in Prevalence of Hypertension between Black and White Americans

项目摘要 在美国成年人中，高血压（HTN）是发病的主要原因， and mortality.我们建议区分睡眠和昼夜节律机制的相对贡献， 与欧洲裔美国人（白色）成年人相比，非洲裔美国人（黑人）成年人的HTN风险增加。的 这项研究的科学前提部分基于我们最近的工作，即睡眠和昼夜节律 这些机制有助于血压（BP）调节和HTN，以及睡眠和昼夜节律调节 在黑人和白色种族之间有区别。创新之处在于了解这些睡眠和 昼夜节律因素机械地解释了HTN中的这种种族差异。最近的研究表明， 更差的睡眠和更短的昼夜节律周期，导致相对于昼夜节律更早睡眠的趋势 相位血压通常在睡眠期间下降，这似乎是保护性的，因为睡眠与血压之间存在关联。 夜间与日间BP相比下降<10%（所谓的非下降BP）和更多的不良CV事件， mortality.黑人增加了这种危险的非浸渍24小时血压波动的患病率。最近我们 发现了一个强大的内源性昼夜节律的血压，无关的活动或睡眠，与昼夜下降， 血压在整个生物夜间，可能有助于夜间血压下降。BP的日变化是 昼夜不同行为对BP影响的总和结果（例如，睡觉，醒来， 运动，其他压力）和昼夜节律系统对BP的影响。我们计划研究这些相互作用的 在26名黑人和26名白色成年人中，年龄在40-60岁之间，以确定睡眠和昼夜节律机制， 可能导致黑人总体血压升高，夜间血压下降减少。这将通过使用 强化多日方案，将睡眠-觉醒周期调整为20小时，以便所有行为均匀发生 在恒定的昏暗光下，在所有的昼夜节律相位上（以避免光重置昼夜节律相位）。睡眠将是 通过多导睡眠图和核心体温的昼夜节律相进行评估。通过学习标准化 行为和调节BP在睡眠和行为压力在所有昼夜节律阶段，该协议 将使我们能够确定，与对照组相比， 白色是由于睡眠不好，同时控制昼夜节律相位（目标1）;降低血压反应， 标准化的昼夜行为变化（如慢波期间血压降低较少 睡眠和/或运动后低血压减少（目标2）;或血压昼夜节律幅度降低（目标3）。 在所有分析中，将调整社会经济状况和压力暴露史。本研究将 第一次区分睡眠，昼夜节律和行为机制对非下降BP的贡献 在黑人中的概况，并为优化依赖于机制的治疗奠定基础， 睡眠、昼夜节律或行为，并提高了HTN的理想治疗可能因以下因素而异的可能性： 比赛这项研究最终将有助于改善HTN黑人人群的健康和生存。

Project Summary In US adults, there are large, unexplained racial disparities in hypertension (HTN), a leading cause of morbidity and mortality. We propose to distinguish the relative contribution of sleep and circadian mechanisms to the increased risk for HTN in African American (Black) adults compared to European American (White) adults. The scientific premise for the proposed research, based partly on our recent work, is that both sleep and circadian mechanisms contribute to blood pressure (BP) regulation and HTN, and both sleep and circadian regulation differ between Black and White races. The innovation is to understand to what degree these sleep and circadian factors mechanistically explain this racial disparity in HTN. Recent work shows that Blacks have poorer sleep and a shorter circadian period, resulting in a tendency towards earlier sleep relative to circadian phase. BP usually decreases during sleep and this appears protective as there is an association between a <10% drop in the nocturnal vs. daytime BP (the so-called non-dipping BP) and more adverse CV events and mortality. Blacks have increased prevalence of this dangerous non-dipping 24-h BP fluctuation. Recently, we discovered a robust endogenous circadian rhythm in BP, unrelated to activity or sleep, with a circadian drop in BP across the biological night that likely contributes to nocturnal BP dipping. The diurnal variation in BP is the result of a summation of the effects on BP of varied behaviors across the day and night (e.g., sleep, waking up, exercise, other stresses) and the effects on BP of the circadian system. We plan to examine these interacting factors in 26 Black and 26 White adults, aged 40-60 years, to determine sleep and circadian mechanisms that may contribute to higher overall BP and reduced nocturnal drop in BP in Blacks. This will be achieved by using an intensive multi-day protocol where sleep-wake cycles are adjusted to 20-h so all behaviors occur evenly across all circadian phases while in a constant dim light (to avoid light resetting circadian phase). Sleep will be assessed with polysomnography and circadian phases by core body temperature. By studying standardized behaviors and regulators of BP during sleep and behavioral stresses across all circadian phases, this protocol will allow us to determine if the higher overall BP and reduced nocturnal drop in BP in Blacks compared to Whites is due to poor sleep, while controlling for circadian phase (Aim 1); reduced BP responses to standardized behavioral changes across the day and night (such as less reduction in BP during slow-wave sleep and/or reduced post-exercise hypotension (Aim 2); or reduced circadian amplitude of BP (Aim 3). Socioeconomic status and history of stress exposures will be adjusted for in all analyses. This study will be the first to distinguish the contributions of sleep, circadian and behavioral mechanisms to the non-dipping BP profile in Blacks and lay the groundwork for optimizing therapies dependent on mechanisms, such as targeting sleep, circadian rhythmicity, or behaviors, and raising the possibility that ideal therapy for HTN may differ by race. This research will ultimately help to improve health and survival in black populations with HTN.