Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis

Aiden J. CHAUNTRY; Justin B. MOORE; Teresa SEEMAN; Steven J. SHEA; Richard P. SLOAN; Anna C. WHITTAKER; Eli PUTERMAN; Anne I. TURNER; William P. TYNE; Mark J. HUTSON; Mark P. FUNNELL; Gabriel ZIEFF; Brook M. GELETA; Keeron STONE; Erik D. HANSON; Lee STONER; Michael P. BANCKS

doi:10.1016/j.psyneuen.2025.107657

Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis

Aiden J. CHAUNTRY, Justin B. MOORE, Teresa SEEMAN, Steven J. SHEA, Richard P. SLOAN, Anna C. WHITTAKER, Eli PUTERMAN, Anne I. TURNER, William P. TYNE, Mark J. HUTSON, Mark P. FUNNELL, Gabriel ZIEFF, Brook M. GELETA, Keeron STONE, Erik D. HANSON, Lee STONER, Michael P. BANCKS

Research output: Contribution to journal › Article › peer-review

Abstract

Background
Dysregulated psychobiological reactivity to acute psychological stress is associated with subclinical cardiovascular disease (CVD) risk, but its association with clinical CVD and mortality remains unclear—especially when considering both exaggerated and blunted responses, non-cardiovascular biomarkers, and potential racial/ethnic differences. This study aimed to test (1) relationships between multi-system stress reactivity and CVD/mortality, and (2) effect modification by race/ethnicity.
Methods
Participants were CVD-free adults (N = 957, age=69 ± 9 years, 56 % female, 27 % non-Hispanic White, 32 % non-Hispanic Black, 41 % Hispanic) enrolled in the Multi-Ethnic Study of Atherosclerosis. The following responses to a standardized psychological stress protocol were recorded: blood pressure (BP), heart rate, heart rate variability (HRV), salivary alpha-amylase (sAA), and cortisol. Participants were followed for a median of 8 years. Covariate-adjusted Cox proportional hazard models investigated associations of stress reactivity (baseline-to-stress changes: low/blunted: ≤25th percentile; intermediate/moderate [reference]: 26–74th; high/exaggerated: ≥75th) with incident CVD (N = 111) and all-cause mortality (N = 114). Race/ethnicity was tested as an effect modifier.
Results
Stress reactivity was not linked with CVD incidence. Blunted diastolic BP reactivity was associated with premature all-cause mortality (HR=1.92, 95 % CI: 1.03—3.56). Exaggerated (HR=0.58, 95 % CI: 0.35—0.98) and blunted (HR=0.52, 95 % CI: 0.30—0.89) sAA reactivity were associated with reduced mortality risk. Race/ethnicity was not an effect modifier (all p for interaction > 0.05).
Conclusions
Blunted DBP reactivity may serve as an early marker of increased mortality risk; randomized trials should test whether interventions that normalize DBP reactivity improve long-term survival. Further research should explore why dysregulated sAA reactivity was associated with lower mortality risk.

Original language	English
Article number	107657
Pages (from-to)	1-11
Number of pages	11
Journal	Psychoneuroendocrinology
Volume	183
Early online date	17 Oct 2025
DOIs	https://doi.org/10.1016/j.psyneuen.2025.107657
Publication status	Published online - 17 Oct 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Ltd.

Data Access Statement

Data from the MESA study are publicly available through request from the Biologic Specimen and Data Repository Information Coordinating Center of the National Institutes of Health: https://biolincc.nhlbi.nih.gov/studies/mesa/. The SAS code used in the manuscript is available upon reasonable request by emailing the corresponding author.

Funding

The MESA was supported by contracts 75N92020D00001, HHSN268201500003I, N01‐HC‐95159, 75N92020D00005, N01‐HC‐95160, 75N92020D00002, N01‐HC‐95161, 75N92020D00003, N01‐HC‐95162, 75N92020D00006, N01‐HC‐95163, 75N92020D00004, N01‐HC‐95164, 75N92020D00007, N01‐ HC‐95165, N01‐HC‐95166, N01‐HC‐95167, N01‐HC‐95168, and N01‐HC‐95169 from the National Heart, Lung, and Blood Institute, and by grants UL1‐TR‐000040, UL1‐TR‐001079, and UL1‐TR‐001420 from the National Center for Advancing Translational Sciences (NCATS). AJC, JBM, EDH and LS are supported by National Heart, Lung, and Blood Institute Grants R01HL157187 and R01HL162805A. MPF is supported by the NIHR Applied Research Collaboration East Midlands (ARC EM). The funding agencies played no role in the design of the study, data analysis and interpretation, manuscript preparation, or the decision to publish the findings.

Keywords

Acute stress
physiological responses
chronic disease prevention
stress reactivity
reactivity hypothesis
Chronic disease prevention
Reactivity hypothesis
Physiological responses
Stress reactivity
Cardiovascular Diseases/mortality
Heart Rate/physiology
Humans
Middle Aged
Biomarkers/analysis
Male
Atherosclerosis/ethnology
Female
Blood Pressure/physiology
Risk Factors
Hydrocortisone/analysis
Saliva/chemistry
Salivary alpha-Amylases/analysis
Ethnicity
Stress, Psychological/physiopathology
Aged

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.psyneuen.2025.107657

Cite this

CHAUNTRY, A. J., MOORE, J. B., SEEMAN, T., SHEA, S. J., SLOAN, R. P., WHITTAKER, A. C., PUTERMAN, E., TURNER, A. I., TYNE, W. P., HUTSON, M. J., FUNNELL, M. P., ZIEFF, G., GELETA, B. M., STONE, K., HANSON, E. D., STONER, L., & BANCKS, M. P. (2026). Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis. Psychoneuroendocrinology, 183, 1-11. Article 107657. Advance online publication. https://doi.org/10.1016/j.psyneuen.2025.107657

@article{8f7b0a73615f4c7795b6693ce3b1c2d7,

title = "Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis",

abstract = "Background Dysregulated psychobiological reactivity to acute psychological stress is associated with subclinical cardiovascular disease (CVD) risk, but its association with clinical CVD and mortality remains unclear—especially when considering both exaggerated and blunted responses, non-cardiovascular biomarkers, and potential racial/ethnic differences. This study aimed to test (1) relationships between multi-system stress reactivity and CVD/mortality, and (2) effect modification by race/ethnicity. Methods Participants were CVD-free adults (N = 957, age=69 ± 9 years, 56 \% female, 27 \% non-Hispanic White, 32 \% non-Hispanic Black, 41 \% Hispanic) enrolled in the Multi-Ethnic Study of Atherosclerosis. The following responses to a standardized psychological stress protocol were recorded: blood pressure (BP), heart rate, heart rate variability (HRV), salivary alpha-amylase (sAA), and cortisol. Participants were followed for a median of 8 years. Covariate-adjusted Cox proportional hazard models investigated associations of stress reactivity (baseline-to-stress changes: low/blunted: ≤25th percentile; intermediate/moderate [reference]: 26–74th; high/exaggerated: ≥75th) with incident CVD (N = 111) and all-cause mortality (N = 114). Race/ethnicity was tested as an effect modifier. Results Stress reactivity was not linked with CVD incidence. Blunted diastolic BP reactivity was associated with premature all-cause mortality (HR=1.92, 95 \% CI: 1.03—3.56). Exaggerated (HR=0.58, 95 \% CI: 0.35—0.98) and blunted (HR=0.52, 95 \% CI: 0.30—0.89) sAA reactivity were associated with reduced mortality risk. Race/ethnicity was not an effect modifier (all p for interaction > 0.05). Conclusions Blunted DBP reactivity may serve as an early marker of increased mortality risk; randomized trials should test whether interventions that normalize DBP reactivity improve long-term survival. Further research should explore why dysregulated sAA reactivity was associated with lower mortality risk.",

keywords = "Acute stress, physiological responses, chronic disease prevention, stress reactivity, reactivity hypothesis, Chronic disease prevention, Reactivity hypothesis, Physiological responses, Stress reactivity, Cardiovascular Diseases/mortality, Heart Rate/physiology, Humans, Middle Aged, Biomarkers/analysis, Male, Atherosclerosis/ethnology, Female, Blood Pressure/physiology, Risk Factors, Hydrocortisone/analysis, Saliva/chemistry, Salivary alpha-Amylases/analysis, Ethnicity, Stress, Psychological/physiopathology, Aged",

author = "CHAUNTRY, \{Aiden J.\} and MOORE, \{Justin B.\} and Teresa SEEMAN and SHEA, \{Steven J.\} and SLOAN, \{Richard P.\} and WHITTAKER, \{Anna C.\} and Eli PUTERMAN and TURNER, \{Anne I.\} and TYNE, \{William P.\} and HUTSON, \{Mark J.\} and FUNNELL, \{Mark P.\} and Gabriel ZIEFF and GELETA, \{Brook M.\} and Keeron STONE and HANSON, \{Erik D.\} and Lee STONER and BANCKS, \{Michael P.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Ltd.",

year = "2025",

month = oct,

day = "17",

doi = "10.1016/j.psyneuen.2025.107657",

language = "English",

volume = "183",

pages = "1--11",

journal = "Psychoneuroendocrinology",

issn = "0306-4530",

publisher = "Elsevier Ltd",

}

CHAUNTRY, AJ, MOORE, JB, SEEMAN, T, SHEA, SJ, SLOAN, RP, WHITTAKER, AC, PUTERMAN, E, TURNER, AI, TYNE, WP, HUTSON, MJ, FUNNELL, MP, ZIEFF, G, GELETA, BM, STONE, K, HANSON, ED, STONER, L & BANCKS, MP 2026, 'Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis', Psychoneuroendocrinology, vol. 183, 107657, pp. 1-11. https://doi.org/10.1016/j.psyneuen.2025.107657

TY - JOUR

T1 - Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis

AU - CHAUNTRY, Aiden J.

AU - MOORE, Justin B.

AU - SEEMAN, Teresa

AU - SHEA, Steven J.

AU - SLOAN, Richard P.

AU - WHITTAKER, Anna C.

AU - PUTERMAN, Eli

AU - TURNER, Anne I.

AU - TYNE, William P.

AU - HUTSON, Mark J.

AU - FUNNELL, Mark P.

AU - ZIEFF, Gabriel

AU - GELETA, Brook M.

AU - STONE, Keeron

AU - HANSON, Erik D.

AU - STONER, Lee

AU - BANCKS, Michael P.

PY - 2025/10/17

Y1 - 2025/10/17

N2 - Background Dysregulated psychobiological reactivity to acute psychological stress is associated with subclinical cardiovascular disease (CVD) risk, but its association with clinical CVD and mortality remains unclear—especially when considering both exaggerated and blunted responses, non-cardiovascular biomarkers, and potential racial/ethnic differences. This study aimed to test (1) relationships between multi-system stress reactivity and CVD/mortality, and (2) effect modification by race/ethnicity. Methods Participants were CVD-free adults (N = 957, age=69 ± 9 years, 56 % female, 27 % non-Hispanic White, 32 % non-Hispanic Black, 41 % Hispanic) enrolled in the Multi-Ethnic Study of Atherosclerosis. The following responses to a standardized psychological stress protocol were recorded: blood pressure (BP), heart rate, heart rate variability (HRV), salivary alpha-amylase (sAA), and cortisol. Participants were followed for a median of 8 years. Covariate-adjusted Cox proportional hazard models investigated associations of stress reactivity (baseline-to-stress changes: low/blunted: ≤25th percentile; intermediate/moderate [reference]: 26–74th; high/exaggerated: ≥75th) with incident CVD (N = 111) and all-cause mortality (N = 114). Race/ethnicity was tested as an effect modifier. Results Stress reactivity was not linked with CVD incidence. Blunted diastolic BP reactivity was associated with premature all-cause mortality (HR=1.92, 95 % CI: 1.03—3.56). Exaggerated (HR=0.58, 95 % CI: 0.35—0.98) and blunted (HR=0.52, 95 % CI: 0.30—0.89) sAA reactivity were associated with reduced mortality risk. Race/ethnicity was not an effect modifier (all p for interaction > 0.05). Conclusions Blunted DBP reactivity may serve as an early marker of increased mortality risk; randomized trials should test whether interventions that normalize DBP reactivity improve long-term survival. Further research should explore why dysregulated sAA reactivity was associated with lower mortality risk.

AB - Background Dysregulated psychobiological reactivity to acute psychological stress is associated with subclinical cardiovascular disease (CVD) risk, but its association with clinical CVD and mortality remains unclear—especially when considering both exaggerated and blunted responses, non-cardiovascular biomarkers, and potential racial/ethnic differences. This study aimed to test (1) relationships between multi-system stress reactivity and CVD/mortality, and (2) effect modification by race/ethnicity. Methods Participants were CVD-free adults (N = 957, age=69 ± 9 years, 56 % female, 27 % non-Hispanic White, 32 % non-Hispanic Black, 41 % Hispanic) enrolled in the Multi-Ethnic Study of Atherosclerosis. The following responses to a standardized psychological stress protocol were recorded: blood pressure (BP), heart rate, heart rate variability (HRV), salivary alpha-amylase (sAA), and cortisol. Participants were followed for a median of 8 years. Covariate-adjusted Cox proportional hazard models investigated associations of stress reactivity (baseline-to-stress changes: low/blunted: ≤25th percentile; intermediate/moderate [reference]: 26–74th; high/exaggerated: ≥75th) with incident CVD (N = 111) and all-cause mortality (N = 114). Race/ethnicity was tested as an effect modifier. Results Stress reactivity was not linked with CVD incidence. Blunted diastolic BP reactivity was associated with premature all-cause mortality (HR=1.92, 95 % CI: 1.03—3.56). Exaggerated (HR=0.58, 95 % CI: 0.35—0.98) and blunted (HR=0.52, 95 % CI: 0.30—0.89) sAA reactivity were associated with reduced mortality risk. Race/ethnicity was not an effect modifier (all p for interaction > 0.05). Conclusions Blunted DBP reactivity may serve as an early marker of increased mortality risk; randomized trials should test whether interventions that normalize DBP reactivity improve long-term survival. Further research should explore why dysregulated sAA reactivity was associated with lower mortality risk.

KW - Acute stress

KW - physiological responses

KW - chronic disease prevention

KW - stress reactivity

KW - reactivity hypothesis

KW - Chronic disease prevention

KW - Reactivity hypothesis

KW - Physiological responses

KW - Stress reactivity

KW - Cardiovascular Diseases/mortality

KW - Heart Rate/physiology

KW - Humans

KW - Middle Aged

KW - Biomarkers/analysis

KW - Male

KW - Atherosclerosis/ethnology

KW - Female

KW - Blood Pressure/physiology

KW - Risk Factors

KW - Hydrocortisone/analysis

KW - Saliva/chemistry

KW - Salivary alpha-Amylases/analysis

KW - Ethnicity

KW - Stress, Psychological/physiopathology

KW - Aged

UR - https://www.scopus.com/pages/publications/105022158988

U2 - 10.1016/j.psyneuen.2025.107657

DO - 10.1016/j.psyneuen.2025.107657

M3 - Article

C2 - 41135261

SN - 0306-4530

VL - 183

SP - 1

EP - 11

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

M1 - 107657

ER -

Psychobiological Reactivity to Acute Psychological Stress as a Predictor of Cardiovascular Disease and Mortality: The Multi-Ethnic Study of Atherosclerosis

Abstract

Bibliographical note

Data Access Statement

Funding

Keywords

UN SDGs

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