Mediating pathways that link adverse childhood experiences with cardiovascular disease

Objectives: There is uncertainty about which factors mediate the association between adverse childhood experiences (ACEs) and cardiovascular disease (CVD). This could inform secondary prevention targets.

Study design: Mediation analysis of a prospective cohort study.

Methods: English Longitudinal Study of Ageing (ELSA) wave 3 data (2006/7) were used to measure retrospective exposure to 12 individual ACEs and waves 2 to 4 (2004/5 to 2008/9) data to measure current exposure to potential mediators [smoking, physical activity, alcohol consumption, body mass index, depression, and C-reactive protein (CRP)]. Waves 4 to 9 ELSA data (2008/9 to 2018/19) were used to measure incident CVD. Cumulative ACE exposure was categorised into experiencing 0, 1 to 3, or ≥4 individual ACEs. Associations were tested between ACE categories, potential mediators, and incident CVD, to inform which variables were analysed in causal mediation models.

Results: The analytical cohort consisted of 4547 participants (56% women), with a mean age of 64 years (standard deviation = 9 years). At least one ACE had been experienced by 45% of the cohort, and 24% developed incident CVD over a median follow-up period of 9.7 years (interquartile range: 5.3-11.4 years). After adjusting for potential confounders, experiencing ≥4 ACEs compared with none was associated with incident CVD [odds ratio (OR): 1.55; 95% confidence interval (CI): 1.10, 2.17], and the association of one to three ACEs compared with none was non-significant (OR: 1.08; 95% CI: 0.93, 1.24). There were two statistically significant mediators of the association between ≥4 ACEs and incident CVD: CRP and depression, which accounted for 10.7% and 10.8% of the association, respectively.

Conclusions: Inflammation and depression partially mediated the association between ACEs and CVD. Targeting these factors may reduce the future incidence of CVD.