Hypertension in Hemodialysis Patients

描述(申请人提供)：这个项目的长期目标是了解家庭血压监测在管理高血压方面的作用，容量超负荷在引起高血压中的作用，以及药物治疗在血液透析患者高血压治疗中的作用。我们假设容量控制可以改善血压，降压治疗可以消退长期血液透析患者的左心室肥厚。具体目的：#1.在一项对150名患者进行的随机试验中，我们已经证明容量控制在4周内改善了血液透析患者的高血压，并持续到8周。为了提高对血液透析患者高血压的诊断，预测对超滤的反应，并探索血液透析患者控制高血压的机制，我们对收集的数据进行了4项补充分析。#2.我们建议完成一项正在进行的关于β-受体阻滞剂与血管紧张素转换酶抑制剂为基础的降压治疗对左心室肥厚消退的随机对照试验。方法：应用目的1分析如下：1.为支持使用家庭血压诊断和治疗高血压，我们将检验超滤组家庭血压改善与对照组的关系，以及与动态血压改善的一致性。我们预计，家庭BP和动态BP之间的协议将超过透析单元BP和动态BP之间的协议。2.为了发现容量超负荷的标志物，我们将评估一组预测超滤后血压下降的标志物。我们预计超滤组患者在4个标志物所定义的容量超负荷时，动态血压会有所改善。3.为了评价动态血压作为容量超负荷指标的价值，我们将分析超滤组与对照组动态血压模式变化的关系。我们预计超滤组的动态血压模式将发生根本性改变，如趋势余弦模型所评估的那样。4.为了确定动脉僵硬在引起高血压中的作用，我们将分析超滤对脉搏波速度的改善。我们期望超滤能改善动脉僵硬和动态血压。应用目的2是一项平行分组、主动对照、单中心、随机开放试验，比较赖诺普利和基于β-受体阻滞剂的阿替洛尔治疗的安全性和有效性，透析后每周三次分别给予赖诺普利和β-受体阻滞剂阿替洛尔对超声心动图左室肥厚消退的主要结果变量进行比较。BP控制将通过家庭BP记录来实现。意义：心血管疾病是血液透析患者死亡的主要原因，高血压是心血管疾病的主要贡献者。在此应用中开发的血液透析患者高血压的诊断、管理和治疗策略，当应用于更多的透析患者时，可能会导致更好的血压控制和更好的心血管结果。新颖性：容量指数被开发为过量容量的标志，趋势协方差模型被开发用于分析血液透析患者的血流动力学模式，这些都是我们早期资助的新发现。将这些新模型应用到随机对照试验中，将把数学表达式转变为活的临床工具。公共卫生相关性：心血管疾病死亡是血液透析患者死亡的主要原因。该项目的长期目标是了解家庭血压监测在管理高血压方面的作用，容量超负荷在导致高血压中的作用，以及药物治疗在血液透析患者高血压治疗中的作用。我们假设容量控制可以改善血压，降压治疗可以消退长期血液透析患者的左心室肥厚。

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the utility of home BP monitoring in managing hypertension, role of volume overload in causing hypertension and drug therapy in the treatment of hypertension in hemodialysis patients. We hypothesize that that volume control can improve BP and antihypertensive therapy can regress left ventricular hypertrophy in long-term hemodialysis patients. Specific aims: #1. In a randomized trial of 150 patients we have shown that volume control improves hypertension in hemodialysis patients within 4 weeks that persists at 8 weeks. To improve the diagnosis of hypertension, predict the response to ultrafiltration and explore the mechanisms of hypertension control in hemodialysis patients we propose 4 additional analyses on the data collected. #2. We propose to complete an ongoing randomized controlled trial of beta- blocker versus ACE-inhibitor based antihypertensive therapy in effecting regression of left ventricular hypertrophy. Methods: Aim 1 of the application has 4 analyses which are as follows: 1. To support the use of home BP to diagnose and manage hypertension we will test the relationship of home BP improvement in the ultrafiltration group compared to controls and the agreement with improvement in ambulatory BP. We expect that the agreement between home BP and ambulatory BP will exceed the agreement between dialysis unit BP and ambulatory BP. 2. To uncover the markers of volume overload, we will evaluate a panel of markers that predict BP fall with ultrafiltration. We expect an improvement in ambulatory BP in the ultrafiltration group when patients are volume overloaded as defined by a panel of 4 markers. 3. To evaluate the value of ambulatory BP as a marker of volume overload, we will analyze the relationship of change in patterns of ambulatory BP in the ultrafiltration group compared to controls. We expect that the ultrafiltration group will have fundamental changes in patterns of ambulatory BP as assessed by the trended cosinor model. 4. To determine the contribution of arterial stiffness in causing hypertension, we will analyze the improvement in pulse wave velocity in response to ultrafiltration. We expect that ultrafiltration will lead to improvement in arterial stiffness and ambulatory BP. Aim 2 of the application is a parallel group, active control, single-center, randomized open-label trial comparing the safety and efficacy of lisinopril vs. beta- blocker atenolol-based therapy each administered three times weekly after dialysis on the primary outcome variable of regression of echocardiographic left ventricular hypertrophy. BP control will be achieved by home BP recordings. Significance: Cardiovascular disease is the major cause of death in hemodialysis patients and hypertension a major contributor of cardiovascular disease. The strategies of diagnosis, management and treatment of hypertension in hemodialysis patients developed in this application when applied to a larger population of dialysis patients may result in improved BP control and better cardiovascular outcomes. Novelty: The volume index developed as a marker of excess volume and the trended cosinor model developed to analyze hemodynamic patterns in hemodialysis patients are novel discoveries from our earlier grant. Application of these novel models to randomized controlled trials would transform a mathematical expression to a live clinical tool. PUBLIC HEALTH RELEVANCE: Cardiovascular mortality is the major cause of death in patients on hemodialysis. The long-term goal of this project is to understand the utility of home BP monitoring in managing hypertension, role of volume overload in causing hypertension and drug therapy in the treatment of hypertension in hemodialysis patients. We hypothesize that that volume control can improve BP and antihypertensive therapy can regress left ventricular hypertrophy in long-term hemodialysis patients.