# Midlife cardiovascular stress physiology and preclinical cerebrovascular disease

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $732,593

## Abstract

Abstract
The goal of this project is to determine the extent to which cardiovascular stress physiology in midlife relates
to the severity of preclinical cerebrovascular disease. This goal aligns with NOT-HL-23-002 and the NHLBI
Strategic Vision, which emphasize a need to understand midlife cardiovascular contributions to later life
dementias. Focusing on cardiovascular stress physiology in midlife follows from cumulative evidence
indicating that individuals with a phenotypic tendency to react to acute psychological stressors with
relatively large rises in blood pressure (stressor-evoked blood pressure reactivity) are at risk for
hypertension and adverse cardiovascular outcomes, which themselves are midlife cardiovascular risk factors
for cerebrovascular disease and later life dementias. The mechanistic pathways by which stressor-evoked
blood pressure reactivity may confer cerebrovascular risk are unknown. They are hypothesized in this
project to include peripheral vascular remodeling and dysfunction, manifesting as arterial stiffness,
endothelial dysfunction, and impaired beat-to-beat hemodynamic control. The latter are further
hypothesized to promote preclinical cerebrovascular disease via a substrate for neurovascular damage;
namely, cerebral pulsatility. To test predictions from these as yet unevaluated hypotheses, 3 Specific Aims
are pursued in a community cohort of 538 midlife adults (aged 40-59 years; ~60% women, ~40%
identifying as nonwhite; final analytic N=450 expected after attrition) who are asymptomatic for clinical
cardiovascular disease and cognitive impairment. In a 2-visit protocol, volunteers will complete validated
and reliable protocols to assess: behavioral, social, and biological determinants of cardiovascular and
cerebrovascular health; arterial stiffness, endothelial function, and beat-to-beat hemodynamic control;
cardiovascular stress reactivity; and, cerebral pulsatility and preclinical cerebrovascular disease. Aim 1 tests
whether larger stressor-evoked cardiovascular (blood pressure, cardiac output, and total peripheral
resistance) reactions relate to preclinical cerebrovascular disease markers (greater cerebral pulsatility,
higher white matter lesion burden, decreased hippocampal volume, and increased enlargement of brain
perivascular spaces) in a multivariate structural equation model. Aim 2 tests whether associations between
stressor-evoked cardiovascular reactions and preclinical cerebrovascular disease markers are partly
explained by arterial stiffness, endothelial dysfunction, and beat-to-beat hemodynamic control. Tertiary
Aim 3 explores whether Aim 1-2 effects are moderated by known cardiovascular risks and sex as a biological
variable. The proposed project seeks to characterize the extent to which cardiovascular stress reactivity in
midlife is a specific cardiovascular source of risk for cerebrovascular disease. In this way, the new
information from this project may identify a potentially modifiable and stress-re...

## Key facts

- **NIH application ID:** 10868774
- **Project number:** 5R01HL169990-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Peter J Gianaros
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $732,593
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868774

## Citation

> US National Institutes of Health, RePORTER application 10868774, Midlife cardiovascular stress physiology and preclinical cerebrovascular disease (5R01HL169990-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10868774. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*