# Inflammatory and immune system gene expression as a marker of vulnerability in older adult patients undergoing a cardiovascular procedure

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $23,400

## Abstract

PROJECT SUMMARY
 Due to increasing average life expectancy, along with the high incidence of cardiovascular disease in
aging, more than half of all cardiovascular procedures are performed in adults over 65 years of age. However,
despite overall favorable safety profiles, older adults have an increased susceptibility to adverse outcomes.
Indeed, exposure to cardiovascular procedures intended to promote survival may instead precipitate long-term
disease and disability. A better understanding of resilience and vulnerability (i.e. why some individuals
successfully navigate health stressors while others do not) may help identify physiologic factors that affect
recovery potential and long-term wellbeing. The goal of this work is to take the first steps in identifying a
potentially modifiable molecular indicator of vulnerability in patients with cardiovascular disease.
 Transcatheter aortic valve replacement (TAVR) is a minimally invasive alternative to surgical aortic
valve replacement for those with symptomatic severe aortic stenosis (AS). Although over 70% of TAVR
patients achieve improved quality of life (QoL) and prolonged survival, poor outcomes such as mortality and
functional decline remain common. Clinical factors like the burden of cardiovascular disease, comorbidities,
and frailty predict worse outcomes. Furthermore, preliminary data suggests that increased markers of
inflammation and dysregulated immune activity are associated with worse outcomes, as well. A better
understanding of the relationship between inflammatory and immune activity and outcomes after TAVR may
point to mechanisms mediating vulnerability and suggest targets for intervention.
 Relevant to this, although never before explored in relation to cardiovascular procedures, a specific
gene expression pattern known as the conserved transcriptional response to adversity (CTRA) is associated
with adverse outcomes after exposure to a health stressor. Defined by the simultaneous upregulation of
inflammation and downregulation of innate immune responses, CTRA expression prior to health-stress
exposure predicts adverse events such as poor QoL and mortality. Importantly, CTRA expression is
modifiable, and pharmacologic and behavioral interventions that successfully downregulate CTRA are
associated with improved clinical outcomes. Therefore, this project explores the hypothesis that increased
CTRA expression at baseline, as a marker of inflammatory and immune system dysfunction, will predict
adverse long-term outcomes after TAVR. By identifying gene expression patterns that relate to increased
vulnerability, the results will provide a foundation for future work exploring physiologic mechanisms that
contribute to diminished resilience, and highlight potential targets for therapeutic manipulation to optimize
outcomes. Furthermore, this project will support my professional development through mentored acquisition of
research and leadership skills necessary to become a successful independent...

## Key facts

- **NIH application ID:** 9987453
- **Project number:** 5R03AG064319-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Deena Goldwater
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $23,400
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-10-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987453

## Citation

> US National Institutes of Health, RePORTER application 9987453, Inflammatory and immune system gene expression as a marker of vulnerability in older adult patients undergoing a cardiovascular procedure (5R03AG064319-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987453. Licensed CC0.

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