Sex-Specific Differences in the Association Between Childhood Adversity and Cardiovascular Disease in Adulthood: Evidence From a National Cohort Study

Abstract Background Childhood adversity increases the risk for cardiovascular disease (CVD) in adulthood. Previously proposed mechanisms suggest that the association is mediated by stress reactivity—known to be higher in women—and is aggravated by adult stress, but this has not yet been confirmed. Therefore, we investigated sex differences to better understand possible pathways from childhood adversity to CVD. Methods The National Population Health Survey, a 15-year cohort study of Canadians aged 18-49 years at baseline was used. Logistic regression with interaction terms for sex and stressful life events was used to assess the risk of CVD after childhood adversity. In secondary analyses, we assessed mediation effects of depression, smoking, alcohol, exercise, and diet using the product of coefficient approach. Mediated moderation was subsequently used to explain sex-moderated effects. Results There was a strong association between childhood adversity and CVD (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.56-2.94) for 3+ childhood adversities. The association was stronger with increasing stressful events, and female patients with 3+ stressful events exhibited the highest risk of CVD (OR, 4.40; 95% CI, 1.98-9.75). No association was found in men. Depression, smoking, and poor diet partially mediated the relationship between childhood adversity and CVD (14%, 9%, and 9%, respectively), but differences in these behaviours did not fully explain the sex-specific differences in the mediated moderation analysis. Conclusions The effect of childhood adverse events on CVD is heightened among women, particularly women with stressful adulthoods, and this difference is not mediated by depression, smoking, or poor diet. These findings have important implications for understanding sex differences in CVD risk.