Shared and distinct pathways from anxiety disorder and depression to cardiovascular disease: a UK Biobank prospective cohort study

Aims: Although anxiety and depression increase the risk of cardiovascular disease, no studies have examined their underlying mechanisms systematically, particularly contrasting the difference between the two of them. Our study aimed to examine the extent to which lifestyle, physical and metabolic factors mediate the associations of anxiety and depression with incident CVD. Methods: A prospective cohort study was conducted using UK Biobank. Anxiety, depression, and incident CVD were ascertained through linkage to hospital and death records. A causal mediation analysis was performed for anxiety and depression separately examining multiple potential lifestyle, physical, and metabolic mediators. Cox proportional hazard models and log-linear models were used to derive indirect effect estimates and proportions mediated. Results: A total of 254,695 participants were included. Both anxiety (HR 1.62, 95% CI 1.15 to 2.13) and depression (HR 2.15, 95% CI 1.75 to 2.64) were associated with CVD after adjusting for sociodemographic confounders. The strongest mediators were current smoking and higher waist-hip ratio which accounted for 12.2% and 12.8% of the excess risk from anxiety, and 17.2% and 13.8% from depression, respectively. The strongest metabolic mediators were systolic blood pressure for anxiety (10.2%) and CRP (10.7%) for depression. Systolic blood pressure was the weakest mediator for depression (4.0%). Conclusions: Lifestyle and physical pathways to incident CVD may be common to both anxiety and depression, but shared metabolic pathways seem unlikely. Our findings inform which risk factors to target among people with anxiety or depression in order to reduce their higher risk of developing CVD.