Autonomic reactivity to mental stress is associated with cardiovascular mortality.

Aims: The mechanisms linking acute psychological stress to cardiovascular disease (CVD) mortality are incompletely understood. We studied the relationship of electrocardiographic measures of autonomic dysfunction during acute mental stress provocation and CVD death. Methods and results: In a pooled cohort of 765 participants with stable CVD from two related studies, we collected Holter data during standardized laboratory-based mental stress testing with a speech task and followed them for events. We assessed autonomic function using low-frequency (LF) heart rate variability (HRV) in 5-min intervals before, during, and after stress induction, and specifically examined changes from rest to stress. We employed cause-specific survival models to examine its association with CVD and all-cause mortality, controlling for demographic and CVD risk factors. The mean (SD) age was 58 (10) years, 35% were women, and 44% self-identified as Black. After a median follow-up of 5.6 years, 37 (5%) died from CVD causes. A stress-induced LF HRV decrease (67% of sample), vs. increase, was associated with a hazard ratio (HR) of 3.48 (95% confidence interval-3.25, 3.73) for CVD mortality. Low rest LF HRV (bottom quartile) was also independently associated with CVD mortality, HR = 1.75 (1.58, 1.94), vs. normal rest LF HRV (upper three quartiles). The combination of stress-induced LF HRV decrease and low rest LF HRV was associated with HR = 5.73 (5.33, 6.15) vs. the normal stress/rest LF HRV reference. We found similar results with HF HRV. Conclusion: Stress-induced LF HRV decrease and low rest LF HRV are both independently and additively associated with a higher CVD mortality risk. Additional research is needed to assess whether targeting autonomic dysfunction may improve CVD outcomes.