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

• 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
• 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

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.

项目摘要 心肌纤维化在慢性肾脏疾病(CKD)患者中非常常见，是一种强烈的 主要心血管不良事件(CV)和死亡率的独立预测因子。而在回归的同时 心肌纤维化可能会减少后续的心血管事件和死亡，而不依赖于血压，风险 心肌纤维化的因素还没有完全定义。我们研究团队产生的新数据显示 血清碳酸氢盐水平异常导致心力衰竭风险增加。然而，有几个基本要素 关于血清碳酸氢盐和不良心血管结局之间的因果关系的问题仍然存在。 此外，高血压治疗、酸碱平衡、心肌纤维化消退和 简历事件的减少并不是很好的理解。Sprint研究是一个独特的机会，可以有效地解决 这些重要的问题。Sprint是一项随机对照临床试验，以确定强化 与标准相比，降低收缩压(&lt；120毫米汞柱)将减少心血管事件 对照组(&lt；140毫米汞柱)。建议的Sprint-心肌纤维化辅助研究创新性地组装 理想的资源组合：心肌纤维化的有效心脏生物标记物，最新 心血管磁共振成像(MRI)技术，一种新的干预措施，并大规模随机 临床试验。它将招募1000名参与者，并通过生物标记物和非造影剂测量心肌纤维化。 基线和18个月随访时的心脏MRI T1图，以解决以下假设： 假设1：据评估，血清碳酸氢盐水平低与心肌纤维化指数高有关。 通过循环血清生物标记物和非对比心脏MRI T1图；假设2：在18个月的随访中- 与标准对照组相比，强化降压组的心肌纤维化程度减轻 假设3：18个月随访时心肌纤维化的改善将与 随着简历事件的减少。作为一个探索性的目标，我们将检验心肌纤维化是一种 在血清碳酸氢盐水平和不良心血管结局之间的联系中起中介作用。这将使研究能够 探索在实验范围内强化降压的潜在机制 Sprint影响心肌纤维化和随后的心血管事件。通过确定以下变化 这些更新颖的心脏MRI T1标记物和血清生物标志物测量密集的收缩 在降低血压方面，它还将为它们可能被纳入未来的试验奠定基础。 Sprint-心肌纤维化将测试原本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，提供关键的机制 有助于解释Sprint结果的信息，并促进我们对心肌纤维化的理解 在CKD及其管理方面。