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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.

项目总结

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.