# Effect of physical rehabilitation on molecular markers of frailty in heart failure

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $501,631

## Abstract

PROJECT SUMMARY/ABSTRACT
Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by functional impairment, is highly
prevalent in older persons, causes substantial morbidity, and has limited treatment options. An emerging view
of HFpEF is that it represents a systemic geriatric condition resulting from accelerated biological aging of multiple
organ systems, underscoring the clinical and pathobiological overlap of HFpEF and frailty. The Rehabilitation
Therapy in Older Acute Heart Failure Patients trial (REHAB-HF) randomized 349 hospitalized HF patients to
usual care versus a dedicated physical rehabilitation intervention. At 3 months, the intervention was associated
with meaningful improvements in functional status, 6-minute walk distance, and quality of life and the effects
were more pronounced in individuals with poorer baseline frailty. While these findings highlight the importance
of addressing frailty in HF, current methods to assess frailty in individuals with cardiovascular disease (CVD) are
limited by lack of uniformity, overlap of frailty measures with CVD-related deficits, and lack of precision in
assigning of frailty phenotypes to underlying biological pathways and mechanisms of frailty. In preliminary
studies, we quantified >1000 circulating proteins in ≈800 older adults with aortic stenosis and developed
proteomic signatures of frailty phenotypes observing that: (1) age accounts for limited variance in frailty-
associated proteins; (2) proteomic signatures of frailty are related to non-CVD mortality; and (3) proteins
associated with frailty are involved in classic and novel pathways of metabolism, muscle physiology, fibrosis,
and cachexia. In this R21, we will evaluate how proteomic signatures of frailty respond to an effective intervention
by measuring >700 circulating cardiometabolic/inflammatory proteins in REHAB-HF trial participants with
HFpEF. We hypothesize that alterations in the circulating proteome during a randomized frailty-targeted
intervention will relate to changes in physical function and prioritize biomarkers of aging and frailty. We will test
this hypothesis using 2 integrative Specific Aims (SAs). In SA1, we identify how the circulating proteome changes
with physical rehabilitation in REHAB-HF and how these changes relate to improvements in frailty measures. In
SA2, we evaluate how proteins prioritized in our preliminary data and SA1 relate to multi-organ phenotypes of
healthy aging and physical function in mostly middle-aged participants from the Framingham Heart Study (FHS)
and Coronary Artery Risk Development in Young Adults (CARDA) Study with overlapping proteomic coverage.
Cohorts are diverse by race (CARDIA) and sex and capture a broad age range (FHS) and longitudinal follow-up
in middle adulthood (with serial proteomics; CARDIA). Successful completion of this project will characterize the
modifiability of proteomic signatures of frailty in response to a physical rehabilitation interventio...

## Key facts

- **NIH application ID:** 10864183
- **Project number:** 1R21AG086679-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Matthew G. Nayor
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $501,631
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864183

## Citation

> US National Institutes of Health, RePORTER application 10864183, Effect of physical rehabilitation on molecular markers of frailty in heart failure (1R21AG086679-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10864183. Licensed CC0.

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