Abstract

Aims Although anxiety disorder and depression increase the risk of cardiovascular disease (CVD), few 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 disorder and depression with incident CVD.Methods and results A prospective cohort study was conducted using UK Biobank. Anxiety disorder, depression, and incident CVD were ascertained through linkage to hospital and death records. A causal mediation analysis was performed for anxiety disorder 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. A total of 254 695 participants were included. Both anxiety disorder [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.15-2.30] and depression (HR 2.15, 95% CI 1.75-2.64) were associated with CVD after adjusting for sociodemographic confounders. Among lifestyle and physical factors, the strongest mediators were current smoking and higher waist-hip ratio which accounted for 11.9% and 13.4% of the excess risk from anxiety disorder, and 17.3% and 14.0% from depression, respectively. The strongest metabolic mediators were systolic blood pressure for anxiety disorder (10.4%) and C-reactive protein (10.8%) for depression. Systolic blood pressure was the weakest mediator for depression (4.3%).Conclusion Lifestyle and physical pathways to incident CVD may be common to both anxiety disorder and depression, but shared metabolic pathways seem unlikely. Our findings inform which risk factors to target among people with anxiety disorder or depression in order to reduce their higher risk of developing CVD. Our study examined whether lifestyle, physical, and metabolic factors mediate the associations between anxiety disorder and depression and incident cardiovascular disease and elucidated shared and distinct pathways.Among the lifestyle and physical factors investigated, smoking and central adiposity were the strongest mediators for both anxiety disorder and depression.High systolic blood pressure was the strong metabolic mediator of anxiety disorder whilst C-reactive protein was a major mediator of depression.