Adverse childhood experiences and cardiometabolic biomarkers: A causal analysis

Background: The associations between adverse childhood experiences (ACEs) and cardiometabolic biomarkers need to be further studied. Our objective was to investigate whether ACEs are causally associated with cardiometabolic biomarkers using observational study and two-sample Mendelian randomization (MR) analysis. Methods: The China Health and Retirement Longitudinal Study (CHARLS) data from 2014 to 2015 was used in the observational study. ACEs were divided into 4 groups (0, 1, 2, and 3 or more) according to whether they had experienced 12 items of negative experiences in childhood. A multilevel model was used to estimate the association between ACEs and each cardiometabolic biomarker. Further, we used two-sample MR to identify their potential causality. Results: A total of 11,422 participants (age:45–96) were eligible for the analyses in the observational study. Participants who experienced more ACEs were significantly higher in high-sensitivity C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol (HDL-C) (all P < 0.05). Compared with those without ACE exposure, participants who experienced 3 or more ACEs had significantly lower total cholesterol (P < 0.05). In addition, a stronger association between ACEs and hs-CRP in males, as well as a stronger association between ACEs and HDL-C (P _interaction = 0.036) in participants with higher education levels were observed. Consistently, in two-sample MR, we observed causal associations between DNA methylation loci and those cardiometabolic biomarkers. Conclusion: Our results indicate that ACEs were causally associated with several cardiometabolic biomarkers. Further, adversity-associated DNA methylation loci might reflect buffering mechanisms against childhood adversity, which provides novel insight to the cardiovascular risk interventions.