Mediating pathways that link adverse childhood experiences with cardiovascular disease

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

Mediation analysis of a prospective cohort study.

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.

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.

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