# Mental Stress Reactivity in Women with Coronary Microvascular Dysfunction

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $717,121

## Abstract

Project Summary/Abstract:
Women with signs and symptoms of myocardial ischemia usually undergo coronary angiography to diagnose
obstructive epicardial coronary artery disease (CAD); however, approximately 50% are found to have no
obstructive CAD (defined as <50% epicardial stenosis on clinically indicated coronary angiography) and are
falsely reassured that their symptoms are non-cardiac. Evidence over the past decade indicates that coronary
microvascular dysfunction (CMD)-related ischemia may be an explanation in such cases. CMD is associated
with increased risk of major adverse cardiovascular events (MACE) and an estimated 3 million women are
impacted by CMD. Cardiac positron emission tomography (PET) imaging can detect CMD by quantifying
myocardial flow reserve (MFR). However, therapeutic strategies are poorly developed in CMD, with limited
studies to inform clinicians on treatment of CMD. This therapeutic uncertainty results from the fact that the
underling pathophysiologic mechanisms of CMD are incompletely understood. Women with CMD typically have
a high psychosocial burden and their angina is often induced by psychological stress, which implicates
autonomic nervous system (ANS) dysfunction. Our hypothesis is that in CMD women, sympathetic activation
during psychological stress drives coronary microvascular constriction. In this proposal we will test the
hypothesis that women with CMD have exaggerated sympathetic activation and abnormal vasoreactivity
to mental stress, which predisposes them to adverse outcomes even in the absence of obstructive CAD.
Three groups of post-menopausal women, ages ≥50 years will be compared: (1) symptomatic women with no
obstructive CAD who have CMD (by PET-derived MFR < 2.0) (n=50); (2) symptomatic women with obstructive
CAD (n=50); and (3) asymptomatic reference controls (n=50). Both comparison groups will be age-matched to
the CMD group. We will assess cardiac sympathetic activity (using123I-meta-iodobenzylguanidine (MIBG)
imaging) and autonomic nervous system reactivity to acute mental stress (Aim 1). Vascular reactivity to acute
mental stress will also be assessed (Aim 2). In addition to laboratory-induced mental stress, we propose to
examine the important role of chronic and daily life stress, negative emotions, anginal symptoms and autonomic
imbalance during one week of home monitoring using wearable sensors and a smartphone for real-time data
collection (Aim 3). Anginal hospitalization and quality of life will be assessed at 12 months of follow-up, along
with MACE. Accomplishing these aims will provide the critically important missing link of whether exaggerated
sympathetic activity is predominant in women with CMD. Findings from this work will inform future intervention
efforts centered on the utility of ANS modulation for the management of this high-risk, understudied patient group.

## Key facts

- **NIH application ID:** 10367011
- **Project number:** 1R01HL157311-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Puja Kiran Mehta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $717,121
- **Award type:** 1
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367011

## Citation

> US National Institutes of Health, RePORTER application 10367011, Mental Stress Reactivity in Women with Coronary Microvascular Dysfunction (1R01HL157311-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10367011. Licensed CC0.

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