# Quantifying cardiac structure and function to define the progression to hear failure in African Americans

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $685,735

## Abstract

Heart failure (HF) affects 5.7 million Americans, is associated with a 50% 5-year mortality, and
disproportionately burdens African Americans (AAs), who have a 50% higher prevalence and ~80% higher
incidence of HF compared to white Americans. HF with preserved LVEF (HFpEF) accounts for up to 70% of
prevalent HF in AAs and has no efficacious therapy. A novel, promising, modifiable pathway underlying
HFpEF involves inflammation, nitric oxide (NO) depletion, natriuretic peptides (NPs), and altered cGMP, and
may be especially relevant in AAs who have greater systemic inflammation and an impaired NP response to LV
wall stress compared to whites. The objective of this application is to define the contributions of comorbidity-
driven inflammation with associated nitric oxide (NO) depletion, and of impaired NP response to LV wall
stress, to the development of cardiac dysfunction, and the transition from asymptomatic cardiac dysfunction to
overt HF in AAs. Our central hypothesis is that cardiovascular (especially hypertension, but also coronary
disease, atrial fibrillation), non-cardiac (diabetes, obesity, renal dysfunction), and non-traditional (physical
inactivity) HF risk factors activate inflammatory pathways which, combined with an impaired NP response to
LV wall stress, exaggerate age-related progression in diastolic dysfunction and promote systolic dysfunction via
depressed cGMP activity, ultimately resulting in HF. By leveraging the PI's ongoing funded project to perform
echocardiography in ~800 AA participants in the Jackson Heart Study (JHS; R01HL135008), this proposal will
obtain echos in the remaining ~2,000 JHS participants at the planned 4th study visit in a highly efficient
manner that minimizes participant study burden. The project will also measure LV deformation on ~4,000
echos from JHS Visit 1 (20 years prior), and pathway biomarkers from Visits 1 and 4 to address the following
specific aims: (1) Define the extent to which traditional and non-traditional clinical risk factors predict diastolic
and systolic dysfunction in AAs; (2) Relate inflammatory pathways and NPs known to influence cGMP activity
to key measures of diastolic and systolic dysfunction; (3) Determine the extent to which LV diastolic and
systolic dysfunction predict incident HF in AAs. The contribution of the proposed research will be to define the
temporal progression of LV dysfunction and its clinical predictors, establish the role of a novel and modifiable
biologic pathway in this progression, and quantify its relation to incident HF. This contribution is significant in
defining the importance of a promising biologic pathway targeted by several existing agents that could translate
rapidly into preventative interventions. This proposal is fundamentally innovative in: (1) interrogating novel
biological pathways and non-traditional HF risk factors as potentially underlying HFpEF; (2) focusing on an
understudied population with excess burden of HF and risk factors; and (3)...

## Key facts

- **NIH application ID:** 10248482
- **Project number:** 5R01HL143224-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Amil M Shah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $685,735
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248482

## Citation

> US National Institutes of Health, RePORTER application 10248482, Quantifying cardiac structure and function to define the progression to hear failure in African Americans (5R01HL143224-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248482. Licensed CC0.

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