# Identifying Early Intervention Targets for Reducing Cardiovascular Risk in Posttraumatic Stress

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $801,736

## Abstract

PROJECT SUMMARY
Posttraumatic stress disorder (PTSD) increases risk of incident cardiovascular disease (CVD) by 25-50%. Most
individuals (50-90%) experience a traumatic event in their lifetime, and PTSD is the fifth most common
psychiatric disorder. Experts have now called for increased CVD surveillance after trauma and for PTSD
treatment trials powered to reduce CVD risk. However, both CVD risk and PTSD are complex phenomena that
likely interact in nuanced ways. Therefore, for such efforts to be successful, we must first identify the
mechanisms by which PTSD influences incident CVD risk. Further, we must understand which of the
dimensions underlying PTSD activate those CVD risk mechanisms. This study will determine which PTSD
dimension(s) contribute to endothelial dysfunction, one of the earliest modifiable precursors to CVD. Only three
studies in select trauma-exposed populations (male veterans and police officers) have tested the association of
PTSD symptoms with flow-mediated dilation (FMD), a functional measure of endothelial dysfunction. This early
work points to endothelial dysfunction as a potential mechanism of the PTSD-CVD link, but the limited
generalizability and lack of nuanced measurement of both posttraumatic stress and endothelial dysfunction in
those studies has limited their impact. Indeed, we still do not know whether PTSD and endothelial dysfunction
are associated in individuals from the broader community. Knowledge of which aspects of PTSD are most
“cardiotoxic” is also lacking, so we do not know which posttraumatic stress dimensions to target. Fear
responses are a core component of PTSD with direct biological relevance to cardiovascular function, whereas
the dysphoria dimension of PTSD is considered more auxiliary. In this study, we will examine cross-sectional
and longitudinal associations of PTSD and its underlying dimensions with functional and, secondarily, cellular
measures of endothelial dysfunction (FMD and circulating endothelial cell-derived microparticles, respectively)
in a community-dwelling sample of CVD-free adult men and women with a history of trauma (50% with current
PTSD). In Primary Aim 1, we will test the association of PTSD diagnosis with endothelial dysfunction. In
Primary Aim 2, we will examine which PTSD dimensions (objective measures of fear and dysphoria, as well as
interview-assessed lower-order symptom dimensions) are most strongly associated with endothelial
dysfunction. In a Secondary Aim, we will examine how these PTSD dimensions predict change in endothelial
dysfunction over 2 years in a subset of the sample. Finally, we will explore the role of stress-related biological
mechanisms, including autonomic imbalance, inflammation, and oxidative stress, in the associations of PTSD
dimensions with endothelial dysfunction. This study will provide the strongest evidence to date for a biologically
plausible mechanistic model of PTSD’s influence on incident CVD risk. If our hypotheses are supported, fut...

## Key facts

- **NIH application ID:** 10222755
- **Project number:** 5R01HL139614-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jennifer A Sumner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $801,736
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222755

## Citation

> US National Institutes of Health, RePORTER application 10222755, Identifying Early Intervention Targets for Reducing Cardiovascular Risk in Posttraumatic Stress (5R01HL139614-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10222755. Licensed CC0.

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