Post-traumatic Psychopathology and Cardiovascular Risk: A Danish Case-Control Study of Sex-Specific Associations

There is increasing recognition that trauma exposure and related psychiatric consequences predict cardiovascular disease risk. However, most research has specifically examined post-traumatic stress disorder-despite evidence that a range of psychiatric disorders may follow trauma. We applied machine learning to identify key post-traumatic psychiatric predictors of incident major adverse cardiac and cerebrovascular events (MACCE) in a population-based cohort.

We conducted a case-control study of adults aged ≥18 years, nested within a trauma-exposed cohort of all Denmark residents from 1995 to 2018. Cases (n=43 994) experienced MACCE (non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, cardiovascular death) between 1995 and 2019. Controls (n=175 872) were matched 4:1 on MACCE date, sex, year of trauma, and age at trauma. Machine learning model predictors included a range of psychiatric disorders diagnosed ≤3 years following trauma. Sex-stratified machine learning models were trained using extreme gradient boosting (men: n=91 111; women: n=84 781) and tested in hold-out datasets (men: n=22 777; women: n=21 197). We identified the 15 most important psychiatric disorder predictors of MACCE using Shapley Additive Explanations values.

For men and women, the most important psychiatric predictor of MACCE was alcohol use disorders. Other important psychiatric predictors included depressive disorders, post-traumatic stress disorder/stress-related disorders, brain-related/physiological conditions, and non-substance-induced delirium. Some sex-specific findings also emerged (eg, depressive episodes more important for women than men). Overall, odds ratios in training and testing sets indicated that odds of MACCE were greater among those with (versus without) psychiatric disorders.

Results emphasize the importance of considering a range of psychiatric disorders when assessing cardiovascular risk following trauma.