Mechanisms of Refractory Hypertension

难治性高血压的机制

基本信息

批准号：
9249086
负责人：
DAVID A CALHOUN
金额：
$ 50.11万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-07 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9249086
关键词：
Adrenergic Agents Adrenergic beta-Antagonists Affect Age Aldosterone Antagonists American Antihypertensive Agents Blood Pressure Body Weight Cardiac Volume Cardiovascular system Characteristics Chlorthalidone Clinic Clinical Congestive Heart Failure Development Diagnostic Dietary Sodium Disease Ethnic Origin Etiology Evaluation Event Functional disorder Heart Rate Hour Hyperaldosteronism Hypertension Incidence Laboratories Liquid substance Magnetic Resonance Imaging Measures Medical Myocardial Infarction Norepinephrine Obstructive Sleep Apnea Organ Patients Pharmaceutical Preparations Phenotype Physiological Plasma Play Population Prevalence Prevention strategy Prospective Studies Race Refractory Research Personnel Resistance Resistance development Resistant Hypertension Rest Role Series Severities Sleep Apnea Syndromes Sodium Chloride Sodium-Restricted Diet Stroke Testing Therapeutic Titrations Translating Treatment Failure base beta-adrenergic receptor blood pressure reduction blood pressure regulation cardiovascular risk factor carvedilol design dietary salt experience experimental study high risk high risk population hypertension control insight lifestyle factors prospective public health relevance screening therapy development therapy resistant treatment strategy urinary

项目摘要

DESCRIPTION (provided by applicant): Resistant hypertension refers to patients with difficult-to-treat hypertension, generally defined as needing 3 or more blood pressure medications. It is a common medical disorder, affecting approximately 7-10 million Americans. Within this group of patients with resistant hypertension is a proportion of patients failing antihypertensive treatment in spite of maximum therapy. We propose referring to this antihypertensive treatment failure as refractory hypertension. In a preliminary analysis of our clinical experience over the last several years, we found that the prevalence of refractory hypertension was approximately 10% of patients initially referred for resistant hypertension. If generally true, this would translate int about 1 million Americans. Refractory hypertension has not been previously described. The current application is designed to test hypothesized mechanisms of antihypertensive treatment failure. In our initial analysis of this group of patients, we found evidence of increased sympathetic activity as an important contributing cause antihypertensive treatment failure. This hypothesized excess in adrenergic activity is suggested by higher resting heart rates and by higher levels of urinary norepinephrine levels compared to patients with controlled resistant hypertension. We will test for heightened sympathetic tone in this group of patients by prospectively comparing plasma norepinephrine levels in patients with refractory hypertension to patients with controlled resistant hypertension. We will also determine the antihypertensive benefit of blocking the effects of sympathetic activity with an agent that provides both alpha and beta adrenergic receptor blockade. Persistent intravascular fluid retention has been shown by us and other investigators to be a common cause of resistant hypertension. To what extent refractory hypertension is volume dependent is unknown. In a second series of experiments, we will test the hypothesis that persistent fluid retention contributes importantly to the development of refractory hypertension by comparing cardiac volumes, as measured by magnetic resonance imaging, in patients with refractory versus controlled resistant hypertension. In a second experiment, will compare the antihypertensive benefit of dietary salt restriction in patients with refractory hypertension versus control patients, to determine to what extent salt sensitivity contributes to antihypertensive treatment failure. Lastly, obstructive sleep apnea is extremely common in patients with resistant hypertension and is thought to contribute to difficulty controlling blood pressure. The role that untreated sleep apnea plays in causing refractory hypertension is unknown. The third objective of this application is to determine the prevalence of moderate/severe obstructive sleep apnea in patients with refractory hypertension compared to patients with controlled resistant hypertension. If poorly treated obstructive sleep apnea is common in patients with refractory hypertension, it will indicate an important and potentially reversible cause of antihypertensive treatment failure.

描述（由申请人提供）：耐药性高血压是指难以治疗高血压的患者，通常定义为需要3种或更多的血压药物。这是一种常见的医学障碍，影响了约7-1000万美国人。在这组耐药性高血压的患者中，降压治疗失败的患者比例尽管进行了最大的治疗。我们建议将这种降压治疗失败称为难治性高血压。在对过去几个的临床经验的初步分析中多年来，我们发现难治性高血压的患病率约为最初转诊为耐药性高血压的患者的10％。如果一般而言，这将翻译约100万美国人。难治性高血压先前尚未描述。当前的应用旨在测试降压治疗失败的假设机制。在我们对这组患者的初步分析中，我们发现了同情活动增加的证据，这是重要的导致抗高血压治疗失败。与患有抗性高血压的患者相比，这种假设的肾上腺素能活性过量是由较高的静息心率和更高水平的去甲肾上腺素水平提出的。我们将通过前瞻性地比较具有控制性高血压患者的难治性高血压患者的血浆去甲肾上腺素水平来测试这组患者的同情性张力。我们还将确定与提供Alpha和Beta肾上腺素能受体阻滞的药物的副作用的抗高血压益处。美国和其他研究者已证明持续性血管内液保留率是抗高血压的常见原因。难治性高血压在多大程度上取决于体积。在第二个实验中，我们将检验以下假设：持续的流体保留对发展重要贡献通过磁共振成像测量的心脏体积，对耐火性和受控性高血压的患者进行比较，通过比较心脏体积来测量。在第二个实验中，将比较饮食盐限制对难治性高血压患者与对照患者的降压益处，以确定盐敏感性在多大程度上有助于降压治疗衰竭。最后，阻塞性睡眠呼吸暂停在耐药性高血压患者中极为普遍，被认为有助于控制血压。未经治疗的睡眠呼吸暂停在引起难治性高血压的作用尚不清楚。该应用的第三个目标是确定与有耐药性高血压的患者相比，难治性高血压患者中度/重度阻塞性睡眠呼吸暂停的患病率。如果在难治性高血压患者中常见治疗的阻塞性睡眠呼吸暂停很常见，则将表明降压治疗衰竭的重要且可能可逆的原因。