How does childhood maltreatment influence cardiovascular disease? A sequential causal mediation analysis

Abstract

Background: Childhood maltreatment has been consistently associated with cardiovascular disease (CVD). However, the mechanisms of this relationship are not yet fully understood. We explored the relative contribution of anxiety/depression, smoking, body mass index (BMI) and inflammation (C-reactive protein, CRP) to the association between childhood maltreatment and CVD in men and women aged 40-69 years in the UK.

Methods: We used data from 40 596 men and 59 511 women from UK Biobank. To estimate the indirect effects of childhood maltreatment (physical, sexual and emotional abuse, and emotional and physical neglect) on incident CVD via each of the mediators, we applied a sequential mediation approach.

Results: All forms of maltreatment were associated with increased CVD risk [hazard ratios (HRs) ranging from 1.09 to 1.27]. Together, anxiety/depression, smoking, BMI and inflammation (indexed by CRP) mediated 26-90% of the association between childhood maltreatment and CVD, and the contribution of these mediators differed by type of maltreatment and sex. Anxiety/depression mediated the largest proportion of the association of sexual abuse, emotional abuse and emotional neglect with CVD (accounting for 16-43% of the total effect), especially in women. In men, BMI contributed the most to the indirect effect of associations of physical abuse and physical neglect with CVD; in women, anxiety/depression and BMI had similar contributions.

Conclusions: These findings add to the understanding of how childhood maltreatment affects CVD risk and identify modifiable mediating factors that could potentially reduce the burden of CVD in people exposed to maltreatment in early life.

Keywords: Childhood maltreatment; UK Biobank; cardiovascular disease; intermediate confounding; sequential mediation analysis.