# Late-life trajectories of cardiac function to define pathways of cardiac resilience

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $1,818,837

## Abstract

Heart failure (HF) disproportionately affects older adults, who carry a high burden of cardiovascular risk
factors and experience accelerated decline in cardiac function. Subsets of older adults do not experience
progressive cardiac dysfunction, but the factors related to late-life cardiac resilience are not well defined. This
is a critical barrier – and missed opportunity – to identify novel interventions and treatment targets to prevent
HF. The objective in this application is to define the lifestyle factors, social drivers, and molecular pathways
underlying cardiac resilience in very late life. The central hypothesis is that in addition to optimal risk factor
control, salutary health behaviors (exercise, diet) and favorable structural factors (less social adversity) protect
from age-related cellular senescence (assessable via plasma proteomics) and promote trajectories of preserved
cardiac function in late life. Leveraging rich longitudinal phenotypic data – including echocardiography – of
participants in the community-based Atherosclerosis Risk in Communities (ARIC) study, sequential
echocardiography will be performed in ~2,175 participants attending the 12th study visit (age ~86±4), in
addition to functional assessments and measurement of plasma proteomics. The resulting three serial
echocardiograms over 12 years will be used to identify trajectories of change in cardiac function and to address
the following aims: (1) Define late-life behaviors and factors associated with cardiac resilience; (2) Identify
proteins and protein networks underlying cardiac resilience with particular attention to circulating markers of
cellular senescence; and (3) Determine the association of cardiac resilience with preservation of physical and
neurocognitive function and freedom from frailty. The contribution of the proposed research will be to define
the impact of modifiable individual behaviors and structural factors on trajectories of cardiac function in very
late life, establish the role of a novel and targetable biologic pathway, and quantify the relation of these
trajectories to functional and neurocognitive outcomes highly relevant to older adults. This contribution will be
significant in enabling the identification of persons at high risk of progressive LV dysfunction in very late life
when traditional risk factors perform poorly, and in determining the importance of a promising and targetable
biologic pathway to preserve cardiac function – essential steps to decrease HF-associated morbidity and
mortality. This research proposal is fundamentally innovative in: (1) focusing on longitudinal cardiac imaging
in very late-life (75 to 91 years of age) when data is sparse but CVD burden is high; (2) interrogating a novel
biological pathway (cellular senescence) potentially impacting late-life cardiac, physical, and neurocognitive
function using serial high throughput proteomics integrated with genomic data; and (3) using innovative
analytic approaches to identi...

## Key facts

- **NIH application ID:** 10900454
- **Project number:** 5R01HL135008-07
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Amil M Shah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,818,837
- **Award type:** 5
- **Project period:** 2017-07-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900454

## Citation

> US National Institutes of Health, RePORTER application 10900454, Late-life trajectories of cardiac function to define pathways of cardiac resilience (5R01HL135008-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10900454. Licensed CC0.

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