Real-Time Angiotensin Monitor for Salt Sensitivity

盐敏感性实时血管紧张素监测仪

• 批准号: 7109597
• 负责人: Christopher Hyde
• 金额: $ 15万
• 依托单位: BIOASSESSMENTS, LLC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109597
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; biomedical equipment development; blood pressure; cardiovascular disorder risk; clinical research; computer program /software; computer system design /evaluation; diagnosis design /evaluation; diagnostic tests; electrocardiographic monitor; electrolyte balance; heart rate; human subject; intravenous administration; method development; noninvasive diagnosis; norepinephrine; oral administration; patient oriented research; renin angiotensin system; salt intake; statistics /biometry; sympathetic nervous system

DESCRIPTION (provided by applicant): Dietary salt increases the risk of hypertension for some, but not all, individuals. But no method exists for assessing an individual's risk of salt-sensitive hypertension. We propose to develop an electrophysiological method of continuously monitoring the neurohormonal changes that occur after consuming salt. Our preliminary data show that the low frequency band (LFB) of heart rate variability is a promising marker for assessing salt sensitivity. The salt-sensitive group had virtually no change in LFB in response to a salt load indicating that they were unable to mount an appropriate physiological response to maintain homeostasis after consuming salt. In contrast, the salt-resistant group had a significant change in LFB but minimal increase in blood pressure (BP) after a salt load, that they were able to mount a robust physiological response which maintained appropriate BP after consuming salt. Empirical data suggests that the magnitude of the LFB change is an indicator of the strength of the body's physiological response to a salt load. Our preliminary data also demonstrate that the LFB changes are correlated with 1) the salt-induced increase in BP and 2) the activation/suppression of the neurohormonal systems involved in the maintaining salt balance. Based on the strength of these results, we propose developing a screening method which tracks LFB changes after administering an oral salt bolus. The proposed product will continuously and noninvasively measure the neurohormonal response to a salt load. Innovations include: 1) sufficient statistical power for detecting significant differences with small samples; 2) the ability to track the dynamic response to a salt load; 3) product could be cost-effectively implemented as a software modification to existing ECG instruments; 4) results are based on many cardiac cycles which greatly improves reliability; 5) completely noninvasive; 6) data is updated every 3 minutes thus facilitating the study of the kinetics of the physiological response to salt. Two protocols (oral and intravenous administration of the salt load) will be conducted to evaluate the utility of the proposed product. Three main hypotheses will be tested. First, is the LFB change correlated with the BP change in response to a salt load? Second, is the LFB measure reliable (i.e., is methods variance low)? Third, is the LFB correlated with the neurohormonal mechanisms involved in maintaining salt balance? The proposed product has significant potential for both scientific and clinical contributions. The reduced variability of the proposed product creates a powerful tool for many areas of cardiology research. With additional Phase II studies to confirm reliability and validity, the proposed product could make a significant clinical contribution by providing a rigorously tested method for assessing the individual risk of salt sensitivity, which would pave the way for realizing the promise of personal medicine: optimizing medical treatment on an individual basis.

描述（由申请人提供）：饮食盐增加了某些人但不是全部个人的高血压风险。但是，没有方法可以评估个人患盐敏感性高血压的风险。我们建议开发一种电生理方法，以连续监测食用盐后发生的神经激素变化。我们的初步数据表明，心率变异性的低频带（LFB）是评估盐灵敏度的有希望的标记。盐敏感的群体几乎没有因盐负荷而改变的LFB，这表明他们无法在食用盐后进行适当的生理反应以维持稳态。相比之下，耐盐组的LFB发生了重大变化，但盐负荷后血压（BP）的升高最小，它们能够安装强大的生理反应，该反应在食用盐后保持适当的BP。经验数据表明，LFB变化的幅度是人体对盐负荷的生理反应强度的指标。 我们的初步数据还表明，LFB的变化与1）盐诱导的BP增加和2）2）与维持盐平衡有关的神经激素系统的激活/抑制。根据这些结果的强度，我们提出了一种筛选方法，该方法在施用口服盐推注后跟踪LFB的变化。 所提出的产物将连续和无创测量对盐负荷的神经激素反应。创新包括：1）足够的统计能力来检测小样本的显着差异； 2）跟踪对盐负荷的动态响应的能力； 3）产品可以作为对现有ECG仪器的软件修改而被成本效率地实施； 4）结果基于许多心脏周期，可大大提高可靠性； 5）完全无创； 6）每3分钟更新数据，从而促进了对盐生理反应动力学的研究。 将进行两种方案（口服和静脉注射盐负荷），以评估拟议产品的效用。将检验三个主要假设。首先，LFB变化是否与响应盐负荷的BP变化相关？其次，LFB测量是否可靠（即方法方差较低）？第三，LFB是否与维持盐平衡涉及的神经激素机制相关？ 提出的产品具有科学和临床贡献的巨大潜力。拟议产品的变异性降低为心脏病研究的许多领域创造了强大的工具。借助II期研究确认可靠性和有效性，该提议的产品可以通过提供严格测试的方法来评估个人盐敏感性的风险来做出重大临床贡献，这将为实现个人医学的承诺铺平道路：以个人为基础优化医疗治疗。