# Myocardial Fibrosis in Hypertensive Adults with and without Chronic Kidney Disease

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $361,400

## Abstract

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.

## Key facts

- **NIH application ID:** 10439461
- **Project number:** 5R01HL141846-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** MIRELA AURORA DOBRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $361,400
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439461

## Citation

> US National Institutes of Health, RePORTER application 10439461, Myocardial Fibrosis in Hypertensive Adults with and without Chronic Kidney Disease (5R01HL141846-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439461. Licensed CC0.

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