Psychobiological reactivity to acute psychological stress as a predictor of cardiovascular disease and mortality: The Multi-Ethnic Study of Atherosclerosis

Psychoneuroendocrinology. 2026 Jan:183:107657. doi: 10.1016/j.psyneuen.2025.107657. Epub 2025 Oct 17.

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; Chronic disease prevention; Physiological responses; Reactivity hypothesis; Stress reactivity.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Atherosclerosis* / ethnology
  • Atherosclerosis* / mortality
  • Atherosclerosis* / psychology
  • Biomarkers / analysis
  • Blood Pressure / physiology
  • Cardiovascular Diseases* / ethnology
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / mortality
  • Cardiovascular Diseases* / psychology
  • Ethnicity
  • Female
  • Heart Rate / physiology
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / metabolism
  • Male
  • Middle Aged
  • Risk Factors
  • Saliva / chemistry
  • Salivary alpha-Amylases / analysis
  • Stress, Psychological* / complications
  • Stress, Psychological* / ethnology
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / physiopathology

Substances

  • Biomarkers
  • Hydrocortisone
  • Salivary alpha-Amylases