Background: While childhood and adulthood traumatic experiences have been linked to subsequent cardiovascular disease (CVD), the relationship between life course traumas and CVD and the underpinning pathways are poorly understood. This study aimed to: (1) examine the associations of childhood, adulthood, and lifetime traumas with CVD; (2) examine the associations between diverse life course traumatic profiles and CVD; and (3) examine the extent to which Phenotypic Age (PhenoAge), a well-developed phenotypic aging measure, mediates these associations. Methods: We included 104,939 participants from the UK Biobank who completed the 2016 online mental health questionnaire. CVD outcomes including ischemic heart disease, myocardial infarction, and stroke were ascertained. Childhood, adulthood, and lifetime traumas were categorized into three subgroups (mild, moderate, and severe), respectively. Four life course traumatic profiles were defined as non-severe traumas across life course, non-severe childhood and severe adulthood traumas, severe childhood and non-severe adulthood traumas, and severe traumas across life course based on both childhood and adulthood traumas. PhenoAge was measured using an equation previously developed. Multivariable logistic models and formal mediation analyses were performed. Results: Of 104,939 participants, 7,398 (7.0%) were diagnosed with CVD. Subgroups of childhood, adulthood, and lifetime traumas were associated with CVD, respectively. Furthermore, life course traumatic profiles were significantly associated with CVD. For instance, compared with subgroups experiencing non-severe traumas across life course, those who experienced non-severe childhood and severe adulthood traumas, severe childhood and non-severe adulthood traumas, and severe traumas across life course had higher odd of CVD, with odds ratios of 1.07 (95% confidence interval [CI]: 1.00, 1.15), 1.17 (95% CI: 1.09, 1.25), and 1.33 (95% CI: 1.24, 1.43), respectively. Formal mediation analyses suggested that PhenoAge partially mediated the above associations. For instance, PhenoAge mediated 5.8% of increased CVD events in subgroups who experienced severe childhood traumas, relative to those experiencing mild childhood traumas. Conclusions: Childhood, adulthood, and lifetime traumas, as well as diverse life course traumatic profiles, were associated with CVD. Furthermore, phenotypic aging partially mediated these associations. These findings suggest a potential pathway from life course traumas to CVD through phenotypic aging, and underscore the importance of policy programs targeting traumatic events over the life course in ameliorating inequalities in cardiovascular health.

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