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：
10439461
负责人：
MIRELA AURORA DOBRE
金额：
$ 36.14万
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10439461
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 control blood pressure intervention blood pressure reduction burden of illness cardiac magnetic resonance imaging cardiovascular disorder risk cardiovascular risk factor circulating biomarkers coronary fibrosis follow-up heart damage hemodynamics hypertension treatment hypertensive 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.

项目摘要心肌纤维化在患有慢性肾脏疾病（CKD）的个体中非常普遍，并且很强主要不良心血管（CV）事件和死亡率的独立预测指标。而回归心肌纤维化可能会减少随后的CV事件，而死亡与血压无关，风险心肌纤维化的因素未完全定义。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的心力衰竭风险增加。但是，有几个必不可少的关于血清碳酸氢盐和不良CV结果之间因果关系的问题。此外，高血压治疗，酸碱平衡，心肌纤维化消退和减少简历事件尚不清楚。 Sprint研究是有效解决的独特机会这些重要的问题。 Sprint是一项随机对照临床试验，以确定是否强化与标准控制（<140 mmHg）。拟议的短脊髓心脏纤维化辅助研究创新了理想的资源组合：经过验证的心肌纤维化的心脏生物标志物，最新的心血管磁共振成像（MRI）技术，一种新颖的干预和大型随机性临床试验。它将招募1000名参与者，并通过生物标志物和非对比度测量心肌纤维化心脏MRI T1在基线和18个月的随访中映射以解决以下假设：假设1：低血清碳酸氢盐水平与评估的心肌纤维化指数有关通过循环血清生物标志物和非对比度心脏MRI T1映射；假设2：在18个月时与标准对照相比团体;和假设3：在18个月后随访时心肌纤维化的改善将与随着简历事件的减少。作为探索性目的，我们将检验以下假设：心肌纤维化是一种血清碳酸氢盐水平和不良CV结果之间的联系中的介体。这将使研究能够探索潜在的机制，从而在该范围内进行密集的收缩压降压冲刺会影响心肌纤维化和随后的心血管事件。通过确定变化这些更新颖的心脏MRI T1映射和血清生物标志物测量到密集的收缩期降低血压，它还将为他们在以后的试验中的潜在纳入奠定基础。冲刺的袖心纤维化将检验关键的假设，这些假设否则无法解决，挑战现有的范例，克服先前研究的局限性，提供关键的机制信息以帮助解释冲刺结果，并提高我们对心肌纤维化的理解在CKD及其管理中。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Isolated Diastolic Hypertension and Kidney and Cardiovascular Outcomes in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

DOI：
10.1016/j.xkme.2023.100728
发表时间：
2023-12
期刊：
KIDNEY MEDICINE
影响因子：
3.9
作者：
Al Saleh, Saud;Dobre, Mirela;DeLozier, Sarah;Perez, Jaime;Patil, Nirav;Rahman, Mahboob;Pradhan, Nishigandha
通讯作者：
Pradhan, Nishigandha

Impact of Guidelines on Hypertension Control in the Elderly.