Myocardial Fibrosis in Hypertensive Adults with and without Chronic Kidney Disease

患有或不患有慢性肾病的高血压成人的心肌纤维化

基本信息

批准号：
10215607
负责人：
MIRELA AURORA DOBRE
金额：
$ 36.75万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10215607
关键词：
Acid-Base Equilibrium Acid-Base Imbalance Acidosis Acids Address Adult Aldosterone Ancillary Study Automobile Driving Bicarbonates Biological Markers Blood Pressure Cardiac Cardiovascular Diseases Cardiovascular system Cessation of life Chronic Kidney Failure Congestive Heart Failure Control Groups Data Development Diffuse Disease Elements Endothelin Enrollment Event Fibrosis Functional disorder Future Galectin 3 Heart failure Imaging Techniques Impairment Individual Inflammatory Infrastructure Intervention Intervention Trial Kidney Left Ventricular Function Link Magnetic Resonance Imaging Measurement Measures Mediating Mediator of activation protein Mental Depression Metabolic acidosis Morbidity - disease rate Morphology Myocardial N-terminal Outcome Participant Pathway interactions Patients Population Process Procollagen Type III Randomized Randomized Clinical Trials Randomized Controlled Clinical Trials Randomized Controlled Trials Research Research Design Resources Risk Risk Factors Role Serum Short Interspersed Nucleotide Elements Sodium Bicarbonate Structure Testing Time Ventricular Arrhythmia Work arm attributable mortality base blood pressure intervention blood pressure reduction blood pressure regulation burden of illness cardiovascular disorder risk cardiovascular risk factor circulating biomarkers coronary fibrosis follow-up heart damage hemodynamics hypertension treatment improved indexing innovation insight interstitial mortality novel patient population procollagen type I carboxy terminal peptide prospective randomized trial sudden cardiac death urinary

项目摘要

Project Summary Myocardial fibrosis is very common in individuals with chronic kidney disease (CKD) and is a strong independent predictor of major adverse cardiovascular (CV) events and mortality. While the regression of myocardial fibrosis may reduce subsequent CV events and death independent of blood pressure, the risk factors for myocardial fibrosis are incompletely defined. New data generated by our research team revealed the increased risk of heart failure conferred by abnormal serum bicarbonate levels. However, several essential questions remain regarding the causal relationship between serum bicarbonate and adverse CV outcomes. Also, the critical links between hypertension treatment, acid base balance, myocardial fibrosis regression, and reduction in CV events are not well understood. SPRINT study is a unique opportunity to efficiently address these important questions. SPRINT was a randomized controlled clinical trial to determine whether intensive reduction in systolic blood pressure (<120 mmHg) will reduce cardiovascular events compared to standard control (<140 mmHg). The proposed SPRINT-Myocardial Fibrosis ancillary study innovatively assembles an ideal combination of resources: validated cardiac biomarkers of myocardial fibrosis, the latest cardiovascular magnetic resonance imaging (MRI) techniques, a novel intervention, and a large randomized clinical trial. It will enroll 1000 participants and measure myocardial fibrosis by biomarkers and non-contrast cardiac MRI T1 mapping at baseline and at 18-months follow-up to address the following hypotheses: Hypothesis 1: Low serum bicarbonate level is associated with high indices of myocardial fibrosis as assessed by circulating serum biomarkers and non-contrast cardiac MRI T1 mapping; Hypothesis 2: At 18-months follow- up the intensive blood pressure group will have reduced myocardial fibrosis compared to the standard control group; and Hypothesis 3: The improvements in myocardial fibrosis at 18 months follow-up will be associated with reductions in CV events. As an exploratory aim, we will test the hypothesis that myocardial fibrosis is a mediator in the link between serum bicarbonate levels and adverse CV outcomes. This will enable the study to explore potential mechanisms whereby intensive systolic blood pressure reduction, in the range being tested in SPRINT, influences myocardial fibrosis and subsequent cardiovascular events. By determining the changes of these more novel cardiac MRI T1 mapping and serum biomarkers measurements to the intensive systolic blood pressure reduction, it will also lay the groundwork for their potential inclusion in future trials. SPRINT-Myocardial Fibrosis will test critical hypotheses that would not otherwise be addressable, challenge existing paradigms, overcome limitations of prior studies, provide key mechanistic information to help interpret the SPRINT results, and advance our understanding of myocardial fibrosis in CKD and its management.

项目概要心肌纤维化在慢性肾病 (CKD) 患者中非常常见，并且是一种严重的疾病。主要不良心血管（CV）事件和死亡率的独立预测因子。虽然回归心肌纤维化可能会减少随后的心血管事件和死亡，与血压无关，风险心肌纤维化的因素尚未完全确定。我们的研究团队生成的新数据揭示了血清碳酸氢盐水平异常导致心力衰竭的风险增加。然而，几个必不可少的关于血清碳酸氢盐与不良心血管结果之间的因果关系仍然存在疑问。此外，高血压治疗、酸碱平衡、心肌纤维化消退和心血管事件的减少尚不清楚。 SPRINT 研究是有效解决问题的独特机会这些重要的问题。 SPRINT 是一项随机对照临床试验，旨在确定强化治疗是否有效与标准相比，收缩压降低（<120 mmHg）将减少心血管事件控制（<140 mmHg）。拟议的 SPRINT-心肌纤维化辅助研究创新地汇集了理想的资源组合：经过验证的心肌纤维化心脏生物标志物、最新的心血管磁共振成像（MRI）技术，一种新颖的干预措施，以及大规模的随机研究临床试验。它将招募 1000 名参与者，并通过生物标志物和非对比剂来测量心肌纤维化情况在基线和 18 个月随访时进行心脏 MRI T1 映射，以解决以下假设：假设 1：根据评估，低血清碳酸氢盐水平与高心肌纤维化指数相关通过循环血清生物标志物和非对比心脏 MRI T1 映射；假设 2：18 个月后—— 与标准对照相比，强化血压组的心肌纤维化程度有所减轻团体;假设 3：18 个月随访时心肌纤维化的改善与随着 CV 事件的减少。作为探索性目标，我们将检验心肌纤维化是一种血清碳酸氢盐水平与不良心血管结果之间联系的中介物。这将使该研究能够探索在正在测试的范围内强化收缩压降低的潜在机制 SPRINT，影响心肌纤维化和随后的心血管事件。通过确定的变化这些更新颖的心脏 MRI T1 映射和血清生物标志物测量可用于强化收缩期血压降低，这也将为它们可能纳入未来的试验奠定基础。 SPRINT-心肌纤维化将测试否则无法解决的关键假设，挑战现有范式，克服先前研究的局限性，提供关键机制帮助解释 SPRINT 结果并增进我们对心肌纤维化的理解的信息 CKD 及其管理。