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.

项目摘要高血压（HTN）是美国发病率和死亡率的主要原因，并大致影响美国成年人中有45％。白天，血压（BP）几乎总是更高；但是，相对下降隔夜BP比白天BP更好地预测了整体简历风险。通常，HTN患者分类进入：（1）浸入，平均夜间BP从白天平均值下降≥10％；（2）非浸水，平均夜间bp不会下降10％。超过30％的HTN患者有非浸泡 BP配置文件与广告结果的风险大大增加有关，包括最终器官与HTN下降患者相比，损害和死亡率。目前尚不清楚是什么原因导致非浸泡HTN，但是昼夜节律系统和睡眠可能起作用，因为这两个系统都会影响BP的昼夜变化。我们的目标是确定未经治疗的HTN患者内部昼夜节律的单独贡献并在关联的简历变量（包括交感神经和副交感神经活动，肾素 - 血管紧张素 - 醛固酮系统的估计以及血管内皮功能。我们的具体目的是确定：1）如果BP中的昼夜节律在非浸入HTN中发生了改变，而2）角色在非浸水HTN中睡眠。我们假设：1）BP昼夜节律在非浸水中发生了变化浸入HTN，导致夜间BP下降； 2）睡眠持续时间在非倾角中比浸入HTN，3）缺乏睡眠衰减过夜BP下降HTN的htn降低多于非浸水 htn。探索性的目的是确定睡眠调节是否增加了一夜之间的BP浸入。所有研究将参加32名参与者（16名北斗星，16名非汗水，16名女性和16名男性）。我们将首先，使用参与者家中无人值守的多聚会摄影来量化睡眠持续时间。其次，我们会发现 BP中的昼夜节律通过使用40小时的常规方案，在其中所有参与者都将被监控在实验室中，在半个姿势，昏暗的姿势和没有时间提示。第三，我们将在实验室的昏暗光中进行随机跨界试验，在此期间是否允许睡眠。 BP和机械CV标记在昼夜研究中不断测量跨界试验。在跨界试验中，我们还将使用微功能学和在试验的日子24小时。最后，我们将试用一个为期两周的睡眠调节时间表，包括维持自我选择的就寝时间，以影响过夜BP浸入。这些高度受控的实验将使我们能够记录昼夜节律系统的各个角色睡在非浸泡的HTN中。了解潜在的简历机制将提供潜在的药理 HTN中基于证据的年代疗法的靶标。了解睡眠的作用将提供未来正式测试睡眠扩展或调节的机会，作为非浸入HTN的行为疗法。