Sleep and circadian mechanisms in hypertension

高血压的睡眠和昼夜节律机制

基本信息

批准号：
10597133
负责人：
Saurabh Suhas Thosar
金额：
$ 60.39万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10597133
关键词：
Address Adult Affect Aldosterone Antihypertensive Agents Attenuated Autonomic nervous system Beds Behavior Behavior Therapy Behavioral Biological Blood Pressure Cardiac Cardiovascular system Categories Cessation of life Chronotherapy Circadian Rhythms Classification Clinical Clinical Trials Cross-Over Trials Crossover Design Cues Data Drops Epidemic Equilibrium Event Female Future Goals Guidelines Health Expenditures Home Hour Hypertension IGFBP2 gene Individual Laboratories Laboratory Study Light Measures Minor Monitor Morbidity - disease rate Organ Outcome Participant Patients Pattern Persons Pharmaceutical Preparations Polysomnography Posture Protocols documentation Public Health Randomized Recommendation Renin-Angiotensin-Aldosterone System Research Rest Risk Risk Factors Role Schedule Sleep Sleep Disorders Standardization Syndrome System Testing Time United States Variant Vascular Endothelium Wakefulness Work adverse outcome blood pressure control blood pressure elevation blood pressure reduction blood pressure variability cardiovascular disorder risk cardiovascular risk factor circadian design evidence base experimental study falls hypertensive improved male mortality new therapeutic target normotensive pharmacologic pilot test poor sleep side effect sleep onset sleep pattern

项目摘要

Project Summary Hypertension (HTN) is a leading cause of morbidity and mortality in the United States and affects approximately 45% of US adults. Blood pressure (BP) is almost invariably higher during the day; however, the relative drop in overnight BP is a better predictor of overall CV risk than daytime BP. Generally, patients with HTN are classified into: (1) dipping, where the average nighttime BP drops by ≥10% from the daytime average; and (2) non-dipping, where the average nighttime BP does not dip by 10%. More than 30% of patients with HTN have a non-dipping BP profile, which is associated with a significantly increased risk for adverse outcomes, including end-organ damage, and mortality, compared to patients with dipping HTN. It is unclear what causes non-dipping HTN, but the circadian system and sleep likely play a role because both systems affect the day-night variation in BP. Our goal is to determine, in patients with untreated HTN, the separate contributions of the internal circadian system and sleep to the non-dipping BP profile and the day/night variability in associated CV variables, including estimates of sympathetic and parasympathetic activity, renin-angiotensin-aldosterone system activity, and vascular endothelial function. Our specific aims are to determine: 1) if circadian rhythms in BP are altered in non-dipping HTN and 2) the role of sleep in non-dipping HTN. We hypothesize that: 1) BP circadian rhythms are altered in non-dipping compared to dipping HTN, resulting in a reduced nocturnal BP decline; 2) sleep duration is shorter in non-dipping than dipping HTN, and 3) the absence of sleep attenuates overnight BP drop in dipping HTN more than non-dipping HTN. An exploratory aim is to determine if two weeks of sleep regularization increases overnight BP dipping. Thirty-two participants (16 dippers, 16 non-dippers, 16 females, and 16 males) will partake in all studies. We will first quantify sleep duration using unattended polysomnography in participants’ homes. Second, we will uncover circadian rhythms in BP by employing a 40-h constant routine protocol, where all participants will be monitored in the laboratory during uninterrupted rested wakefulness in a semi-recumbent posture, dim light, and without time cues. Third, we will conduct a randomized crossover trial in dim light in the laboratory, during which overnight sleep is permitted or not. BP and mechanistic CV markers are continuously measured in the circadian study and the crossover trial. In the crossover trial, we will also measure sympathetic activity using microneurography and 24-h BP on the days of the trials. Finally, we will pilot test a two-week sleep regularization schedule, including maintaining a self-selected bedtime, to its impact on overnight BP dipping. These highly controlled experiments will enable us to document the separate roles of the circadian system and sleep in non-dipping HTN. Understanding underlying CV mechanisms will provide potential pharmacological targets for evidence-based chronotherapy in HTN. Understanding the role of sleep will provide future opportunities to formally test sleep extension or regularization as behavioral therapies for non-dipping HTN.

项目概要高血压 (HTN) 是美国发病率和死亡率的主要原因，影响大约 45% 的美国成年人的血压 (BP) 几乎总是在白天升高，但血压却相对下降。夜间血压比白天血压更能预测总体心血管风险。一般来说，高血压患者会被分类。分为：(1) 下降，其中夜间平均血压较白天平均值下降 ≥10%；以及 (2) 非下降；其中平均夜间血压未下降 10% 超过 30% 的高血压患者血压未下降。血压状况，与不良后果（包括终末器官）风险显着增加相关与浸渍型高血压患者相比，目前尚不清楚是什么原因导致非浸渍型高血压。昼夜节律系统和睡眠可能发挥了作用，因为这两个系统都会影响血压的昼夜变化。目标是确定未经治疗的高血压患者内部昼夜节律系统的单独贡献和睡眠时的非下降血压曲线以及相关 CV 变量的日/夜变异性，包括交感神经和副交感神经活动、肾素-血管紧张素-醛固酮系统活动的估计，以及血管内皮功能。我们的具体目标是确定：1）血压的昼夜节律在非浸渍 HTN 中是否发生改变；2）其作用我们破坏了非浸渍 HTN 中睡眠的影响：1）与非浸渍相比，血压昼夜节律发生了变化。浸泡 HTN，导致夜间血压下降减少；2) 睡眠时间比不浸泡的时间短；浸渍 HTN，以及 3) 与不浸渍 HTN 相比，缺乏睡眠更能减弱浸渍 HTN 的夜间血压下降 HTN。一个探索性的目标是确定两周的睡眠规律是否会增加夜间血压下降。 32 名参与者（16 名杓状者、16 名非杓状者、16 名女性和 16 名男性）将参加所有研究。首先，我们将在参与者家中使用无人值守的多导睡眠图来量化睡眠持续时间。通过采用 40 小时恒定常规方案来控制血压的昼夜节律，所有参与者都将受到监测在实验室中，在不间断的休息清醒状态下，以半卧姿势、昏暗的光线和没有第三，我们将在实验室的昏暗光线下进行随机交叉试验，期间过夜。在昼夜节律研究中连续测量是否允许睡眠。在交叉试验中，我们还将使用显微神经描记术测量交感神经活动，最后，我们将试点测试为期两周的睡眠规律化计划，包括试验当天的 24 小时血压。保持自行选择的就寝时间，以影响夜间血压下降。这些高度控制的实验将使我们能够记录昼夜节律系统和了解潜在的 CV 机制将提供潜在的药理学作用。了解睡眠的作用将为 HTN 的循证时间疗法提供未来的目标。有机会正式测试睡眠延长或规律化作为非浸渍性高血压的行为疗法。