# Investigation of Sex and Gender Differences in Cardiovascular Risk in Rural Communities

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $1,021,923

## Abstract

Women living in the rural United States experienced a disproportionate increase in premature coronary heart
disease (CHD) mortality between 2009 and 2017 compared to other demographic groups, which otherwise
enjoyed a reduction in CHD events. Worsening mental health is a growing concern in rural areas and may
disproportionately affect rural women due to constraining gender stereotypes, lack of social and economic
resources, and limited access to care. These factors in turn may increase CHD risk in women through
autonomic, neuroendocrine, and inflammatory response pathways. We anticipate that both gender (social
constructs) and sex (biological factors) and their interplay are implicated. Our overarching hypothesis is that
rural women have disproportionally high exposure to social adversity and psychological stress, leading to sex-
specific hormonal, inflammatory, autonomic, and cardiovascular consequences that collectively increase CHD
risk. We also hypothesize that these effects are more likely to occur during women's reproductive years in part
through alterations in reproductive physiology and inflammation. Partnering with the ongoing RURAL (Risk
Underlying Rural Areas Longitudinal) cohort study, we will study a diverse sample of approximately 3,800
people of age 25-64 years from 10 rural counties in the Southern US undergoing detailed cardiovascular
phenotyping and psychosocial evaluation. We will examine everyday stress using a novel smartphone-based
tool and leverage data from wristband wearables to evaluate sleep and circadian patterns that in our studies
were associated with psychological stress. We will also examine cardiac autonomic function to provide insight
on brain-heart reactivity to daily stress with a novel multi-modal ambulatory heart monitor that measures
electrocardiography (ECG), pulse waveform, respiration, and movement. Finally, we will examine inflammatory
and reproductive hormonal pathways potentially related to both stress and CHD, to help understand the
disproportionately accelerated CHD risk in young women. In aim 1, we examine differences in social adversity
and mental health factors between women and men in rural communities, and in the relationship of these
exposures with cardiometabolic risk profile and subclinical CHD. In aim 2, we will examine differences in daily
stress and stress-related cardiovascular physiology between women and men by conducting a week-long
ecological momentary assessment with physiological monitoring to examine daily perceived mood/stress,
stressful life events, and corresponding autonomic stress responses with a multi-sensor chest patch that
examines both cardiac and vascular autonomic effects. In aim 3, we examine whether social adversity, mental
health factors, and stress in everyday rural life are related to immune alterations (interleukin-6) and
reproductive aging (anti-Mullerian hormone). This study will be the first to examine multifactorial
biopsychosocial determinants underlying dist...

## Key facts

- **NIH application ID:** 10792598
- **Project number:** 5R01HL163998-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Amit Jasvant Shah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,021,923
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792598

## Citation

> US National Institutes of Health, RePORTER application 10792598, Investigation of Sex and Gender Differences in Cardiovascular Risk in Rural Communities (5R01HL163998-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10792598. Licensed CC0.

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