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

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.