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

睡眠和昼夜节律机制导致美国黑人和白人之间高血压患病率的差异

• 批准号: 9921461
• 负责人: STEVEN A SHEA
• 金额: $ 82.95万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-10 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9921461
• 关键词: Accounting; Acute; Adult; African American; American; Behavior; Behavioral; Behavioral Mechanisms; Biological; Black race; Blood Pressure; Body Temperature; Caucasians; Circadian Rhythms; Dangerousness; Diagnostic; Diurnal Rhythm; Drops; Environment; European; Event; Exercise; Exhibits; Health; High Prevalence; Hypertension; Hypotension; Light; Morbidity - disease rate; Organ; Periodicity; Phase; Polysomnography; Prevalence; Protocols documentation; Race; Recording of previous events; Research; Risk; Sleep; Sleep Stages; Sleep Wake Cycle; Sleep disturbances; Slow-Wave Sleep; Socioeconomic Status; Standardization; Stress; System; Testing; Work; aged; base; blood pressure reduction; blood pressure regulation; caucasian American; circadian; circadian regulation; health disparity; improved; innovation; mortality; racial discrimination; racial disparity; response; sleep quality; sleep regulation; social stigma; treatment optimization

PROJECT SUMMARY/ABSTRACT 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.

项目摘要/摘要 在美国成年人中，高血压(HTN)存在巨大的、无法解释的种族差异，高血压是发病率的主要原因 和死亡率。我们建议区分睡眠和昼夜节律机制对 与欧洲裔美国人(白人)相比，非裔美国人(黑人)患HTN的风险更高。这个 这项拟议研究的科学前提是，睡眠和昼夜节律都是基于我们最近的工作 血压调节和HTN的机制，以及睡眠和昼夜节律的调节 黑人和白人之间的区别。创新之处在于了解这些人的睡眠和睡眠程度 昼夜节律因素机械地解释了HTN中的种族差异。最近的研究表明，黑人有 较差的睡眠和较短的昼夜节律，导致相对于昼夜节律有早睡的倾向 相位。血压通常在睡眠期间下降，这似乎是保护性的，因为 夜间血压比白天血压下降10%(所谓的非低血压)，以及更多的不良心血管事件和 死亡率。黑人增加了这种危险的24小时血压波动的患病率。最近，我们 在血压中发现了一个强劲的内源性昼夜节律，与活动或睡眠无关，昼夜节律下降 这可能是夜间血压下降的原因之一。血压的日变化是 白天和夜间不同行为(例如，睡眠，醒来， 运动、其他压力)以及对昼夜节律系统的血压的影响。我们计划研究这些相互作用 年龄在40-60岁的26名黑人和26名白人成年人的因素，以确定睡眠和昼夜节律机制 可能导致黑人总体血压较高，夜间血压下降较少。这将通过使用 一种密集的多天协议，其中睡眠-唤醒周期调整为20-h，以便所有行为均匀发生 在恒定的暗光下跨越所有昼夜节律阶段(以避免光线重置昼夜节律阶段)。睡眠将会是 通过多导睡眠图和核心体温的昼夜节律进行评估。通过学习标准化 睡眠期间血压的行为和调节，以及所有昼夜节律阶段的行为压力，该方案 将使我们能够确定与黑人相比，黑人总体血压更高，夜间血压下降更少 白人是由于睡眠不佳，同时控制昼夜节律(目标1)；血压对 标准化的昼夜行为变化(如慢波时血压下降较少 睡眠和/或运动后低血压减少；目标2)；或血压昼夜幅度降低(目标3)。 社会经济地位和压力暴露的历史将在所有分析中进行调整。这项研究将是 首先区分睡眠、昼夜节律和行为机制对非低血压的贡献 在黑人中简介并为优化依赖于机制的治疗奠定基础，例如靶向 睡眠、昼夜节律性或行为，并增加了HTN的理想治疗方法可能不同于 种族。这项研究最终将有助于改善患有HTN的黑人人口的健康和存活率。