Sleep and Blood Pressure-Related Endothelial Abnormalities

项目摘要/摘要 除了年龄，高血压是全球最主要的心血管疾病风险因素。 在美国，据估计，大约60%的成年人口患有高血压 高血压前期(120-139/80-毫米汞)或高血压(&gt；140/90毫米汞)范围。都是高血压前期 (尤其是收缩压130毫米汞柱)和高血压与心肌梗死风险增加有关。 脑梗塞、心力衰竭、中风和血管疾病。内皮功能障碍是导致 血压升高会增加血管事件的风险。此外，每晚睡眠不足(&lt；7小时/晚) 睡眠质量差不仅与高血压的病因有关，而且也是一种 常见的，常被忽视的，共病。事实上，睡眠时间短和/或睡眠质量差现在被认为是 可能是血压升高的危险因素，也是心血管风险增加的先兆。一次高潮 据报道，高血压成人夜间睡眠不足的情况普遍存在。重要的是，习惯性睡眠 持续时间少于7小时/夜独立地与中风和冠状动脉风险增加相关 疾病。睡眠不足对成人高血压病患者血管内皮功能的影响 压力是未知的。此外，考虑到睡眠时间与质量和血液之间的新关系 压力，睡眠是改善血管的一个重要的、目前被忽视的治疗目标 健康，进而降低高血压成年人的心血管风险。目前的建议 将检验以下假设：1)慢性睡眠不足与内皮细胞减少有关- 依赖一氧化氮介导的血管扩张和内皮组织纤溶酶原激活物释放 血压升高的成年人。此外，内皮血管扩张剂和血管内皮细胞的假设减少 睡眠不足的纤溶功能将至少部分归因于氧化应激增加； 增加睡眠时间和改善睡眠质量(利用个性化的针对性睡眠干预)将 增加内皮依赖的一氧化氮介导的血管扩张和内皮组织类型 血压升高的成人体内纤溶酶原激活物的释放。血管内皮细胞扩张剂和 纤溶功能将至少部分归因于减少氧化应激。为了检验这些假设，124 血压升高的中年成年人(&gt；130/80毫米汞柱)将被研究。内皮血管扩张剂和 纤溶功能将在活体内使用隔离的前臂模型进行评估。拟议的研究将提供 睡眠不足对血管内皮细胞影响的新的临床重要信息 血压升高的成年人的功能。此外，确定可能的心脏保护作用 改善成人睡眠和昼夜生理对血管内皮血管扩张剂和纤溶功能的影响 血压升高在临床上是创新的、新颖的，对开发最佳策略至关重要 (包括主要和辅助)，以降低与血压相关的心血管风险。

PROJECT SUMMARY/ABSTRACT Aside from age, elevated blood pressure is the most predominant cardiovascular disease risk factor worldwide. In the United States it is estimated that ~60% of the adult population have elevated blood pressure in either the prehypertensive (120-139/80-89 mmHg) or hypertensive (>140/90 mmHg) range. Both prehypertension (particularly systolic BP >130 mmHg) and hypertension are associated with increased risk for myocardial infarction, heart failure, stroke and vascular disease. Endothelial dysfunction is a major factor underlying the increased risk of vascular events with elevated blood pressure. In addition, insufficient nightly sleep (<7 hr/night) and poor sleep quality have been linked not only to the etiology of elevated blood pressure but are also a prevalent, often ignored, comorbidity. Indeed, short sleep duration and/or poor sleep quality is now considered to be a plausible risk factor for elevated blood pressure and a harbinger of increased cardiovascular risk. A high prevalence of insufficient nightly sleep has been reported in hypertensive adults. Importantly, habitual sleep duration of less than 7 hr/night is independently associated with an increased risk of stroke and coronary artery disease. The influence of insufficient sleep on vascular endothelial function in adults with elevated blood pressure is unknown. Moreover, given the emerging relation between sleep duration and quality and blood pressure, sleep represents an important, and currently neglected, therapeutic target for improving vascular health and, in turn, reducing cardiovascular risk in adults with elevated blood pressure. The present proposal will test the following hypotheses: 1) that chronic insufficient sleep is associated with diminished endothelium- dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in adults with elevated blood pressure. Furthermore, the postulated diminishment in endothelial vasodilator and fibrinolytic function with insufficient sleep will be due, at least in part, to increased oxidative stress; and 2) increasing sleep duration and improving sleep quality (utilizing individualized targeted sleep interventions) will increase both endothelium-dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in adults with elevated blood pressure. Increases in endothelial vasodilator and fibrinolytic function will be due, at least in part, to reduced oxidative stress. To test these hypotheses, 124 middle-aged adults with elevated blood pressure (>130/80 mmHg) will be studied. Endothelial vasodilator and fibrinolytic function will be assessed, in vivo, using an isolated forearm model. The proposed study will provide new and clinically important information regarding the influence of insufficient sleep on vascular endothelial function in adults with elevated blood pressure. Moreover, determining the possible cardioprotective effects of improving sleep and circadian physiology on vascular endothelial vasodilator and fibrinolytic function in adults with elevated blood pressure is clinically innovative, novel and critical to the development of optimal strategies (both primary and adjunctive) to mitigate blood pressure-related cardiovascular risk.