Adverse childhood experiences are associated with detrimental hemodynamics and elevated circulating endothelin-1 in adolescents and young adults

Growing evidence suggests that adverse childhood experiences (ACEs) increase the risks for coronary heart disease and hypertension in mid and late adulthood. We previously reported that early life stress induces a hyperreactive endothelin-dependent cardiovascular phenotype in a rat model. In the present study, we evaluated whether exposure to ACEs is associated with greater peripheral resistance, arterial stiffness, blood pressure, or elevated circulating endothelin-1 levels in humans. In 221 healthy adolescents and young adults (mean age, 21 years; range, 13-29 years), we found a graded association of ACE exposure with plasma endothelin-1 levels, of which on average 18% and 24% were higher in participants with 1 ACE and ≥2 ACEs, respectively, compared with those with no ACEs (P=0.001). Participants with moderate/severe exposure to ACEs (≥2 ACEs) had significantly higher total peripheral resistance index (+12%), diastolic blood pressure (+5%), and pulse wave velocity (+9%) compared with those who were not exposed. These associations were independent of age, race, sex, body mass index, and childhood socioeconomic status. Our results indicate that early life stress promotes cardiovascular disease risk, specifically detrimental vascular and cardiac function, detectable in young adulthood.