Impact of sex differences in early life stress exposure on cardiovascular risk factors in adolescence

Background and Rationale: Early life stress (ELS) includes emotional abuse, physical trauma, poverty, household dysfunction, and other forms of childhood adversity that occur prior to 18 years of age. ELS has generally been associated with increased cardiovascular disease (CVD) risk and other poor health outcomes in adulthood but affects males and females differently in both humans and animal models. The type, degree, and timing of ELS exposure can be quantified using a variety of validated instruments: Adverse Childhood Experiences (ACE), Children’s Report of Exposure to Violence (CREV), Adolescent Discrimination Distress Index (ADDI), Adolescent Life Change Event Scale (ALCES), and the Childhood Trauma Questionnaire (CTQ). However, few studies have profiled multiple forms of ELS within an adolescent cohort to determine the sex-specific differential impacts on surrogates for future CVD risk. Therefore, in this study we hypothesized that males would have increased exposure to violence, females would have increased exposure to emotional/physical abuse, and both relationships would be associated with worse surrogates for future CVD risk. Methods: We tested this hypothesis in an interim analysis of an ongoing prospective cohort study of ELS in healthy adolescents. Each participant completed a single study visit with a blood draw followed by ACE, CREV, ADDI, ALCES, and CTQ questionnaires to quantify ELS exposure. We measured creatinine-based estimated GFR (eGFR) and plasma uric acid (pro-inflammatory and pro-oxidant molecule) as CVD risk factors and our primary outcomes. We tested associations between each ELS exposure and eGFR/uric acid in the overall population as well as in male and female subgroups to identify sex differences in ELS exposures and CVD risk surrogates. We used Student’s t test to compare means and Pearson’s correlation to analyze linear relationships between continuous variables. Results: We analyzed 163 adolescents enrolled to date. The cohort included 52% males and 48% females and the median (min, max) age was 15 (13-18) years; other demographic features of the cohort were consistent with our local population. We detected sex-specific differences in some ELS exposures, as ALCES scores were significantly higher in females (17.73 ± 6.62 vs. 12.25 ± 6.51; P = .017) while CREV scores were significantly higher in males (1.39 ± 2.26 vs. 0.81 ± 1,24; P = .046); the other ELS exposures were equally distributed between sexes. Only in males, we found trends for positive correlations between ACE scores (r2= 0.203, P = 0.062) and CTQ emotional neglect scores (r2 = 0.199, P = 0.062) with uric acid levels but found no associations between ELS exposures and eGFR. There were no relationships between ELS exposures and either eGFR or uric acid in the female subgroup. Conclusions: We found important sex-specific differences in ELS in adolescents, with greater exposure to violence in males and greater exposure to personal, social, and family changes in females. Males with certain forms of ELS exposure could be at risk for higher uric acid levels, which if validated in our final cohort would provide one mechanistic link between ELS exposure and future cardiovascular disease in adulthood. We speculate that even if ELS exposure in adolescents is unable to be “cured” per se, identifying treatable ELS-mediated mechanisms of future CVD risk is of paramount importance. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.