Hypertension in Hemodialysis Patients

描述（由申请人提供）：本项目的长期目标是了解家庭血压监测在管理高血压中的效用、容量超负荷在引起高血压中的作用以及血液透析患者高血压治疗中的药物治疗。我们假设容量控制可以改善血压，降压治疗可以逆转长期血液透析患者的左心室肥厚。具体目标：#1。在一项150例患者的随机试验中，我们发现容量控制在4周内改善了血液透析患者的高血压，并持续8周。为了提高对高血压的诊断，预测超滤的反应，并探讨血液透析患者高血压控制的机制，我们建议对收集的数据进行4项额外的分析。#2.我们建议完成一项正在进行的随机对照试验，比较β受体阻滞剂与ACE抑制剂为基础的降压治疗对左心室肥厚消退的影响。方法：应用目的1有4个分析：1.为了支持使用家庭血压诊断和管理高血压，我们将测试超滤组与对照组相比家庭血压改善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之间的一致性将超过透析单元BP和动态BP之间的一致性。2.为了揭示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，当患者的容量超负荷（由4项标志物组成）时，超滤组的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标志物的价值，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变化，如趋势余弦模型所评估的那样。4.为了确定动脉僵硬度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。我们预计超滤将导致动脉僵硬度和动态血压的改善。本申请的目的2是一项平行组、活性对照、单中心、随机、开放标签试验，比较赖诺普利与基于β受体阻滞剂阿替洛尔的治疗的安全性和有效性，每种治疗在透析后每周给药三次，主要结局变量为超声心动图左心室肥大消退。将通过家庭BP记录实现BP控制。重要性：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原因。本申请中开发的血液透析患者高血压的诊断、管理和治疗策略在应用于更大的透析患者人群时可能会改善BP控制和更好的心血管结局。新奇：容量指数发展为过量容量的标志物，趋势余弦模型发展为血液透析患者的血流动力学模式分析是我们早期资助的新发现。将这些新模型应用于随机对照试验将把数学表达式转化为实时临床工具。公共卫生相关性：心血管死亡率是血液透析患者的主要死亡原因。本项目的长期目标是了解家庭血压监测在管理高血压中的效用、容量超负荷在引起高血压中的作用以及血液透析患者高血压治疗中的药物治疗。我们假设容量控制可以改善血压，降压治疗可以逆转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.