Sleep and circadian mechanisms in hypertension

项目摘要 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。血压(BP)在白天几乎总是较高的；然而，在 夜间BP比白天BP更能预测整体心血管风险。一般来说，HTN患者是被分类的 进入：(1)下沉，其中平均夜间血压比白天平均下降≥10%；和(2)非下沉， 那里的平均夜间血压不会下降10%。超过30%的HTN患者有非浸泡 BP曲线，这与包括器官末梢在内的不良结局的风险显著增加有关 损害和死亡率，与浸泡HTN的患者相比。目前尚不清楚是什么原因导致HTN不浸泡，但 昼夜节律系统和睡眠可能起到一定作用，因为这两个系统都会影响血压的昼夜变化。我们的 目的是确定未经治疗的HTN患者体内昼夜节律系统的单独作用。 和睡眠与非下降血压曲线和相关CV变量中的昼夜变异性的关系，包括 交感和副交感神经活性、肾素-血管紧张素-醛固酮系统活性的估计 血管内皮功能。 我们的具体目标是确定：1)血压昼夜节律是否在非浸泡HTN中发生改变；2)在 在非浸泡的HTN中睡眠。我们假设：1)血压昼夜节律在非低血压对照中发生改变 2)非潜伏期睡眠时间短于非潜伏期 服用HTN，以及3)睡眠不足对服用HTN的患者夜间血压下降的影响大于未服用HTN的患者 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个参与者(16个勺子，16个非勺子，16个女性和16个男性)将参与所有研究。我们会 首先，在参与者的家中使用无人值守的多导睡眠记录仪来量化睡眠时间。第二，我们将揭开 血压的昼夜节律，采用40小时不变的常规方案，其中所有参与者都将受到监测 在实验室中，在半卧姿、昏暗的光线和不间断的休息清醒状态下 时间在暗示着。第三，我们将在实验室进行暗光下的随机交叉试验，在此期间， 睡觉是允许还是不允许的。在昼夜节律研究中连续测量BP和机械性CV标记物 交叉试验。在交叉试验中，我们还将使用显微神经造影和 试验当天的24小时BP。最后，我们将试行为期两周的睡眠规律化时间表，包括 保持自己选择的就寝时间，以影响夜间血压下降。 这些高度受控的实验将使我们能够记录昼夜节律系统和 睡在非浸泡的HTN中。了解潜在的心血管机制将提供潜在的药理学 HTN循证计时疗法的靶点。了解睡眠的作用将提供未来 正式测试睡眠延长或规律化作为非浸泡HTN的行为疗法的机会。

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.