A large prospective cohort study found that depression and anxiety may be associated with an increased risk of coronary artery disease, with the association for depression being strongest among individuals with high genetic susceptibility.
In the study, published in BMC Medicine, investigators analyzed data from 288,031 participants in the UK Biobank.
The investigators reported that depression was linked to a hazard ratio (HR) of 2.15 (95% confidence interval [CI] = 1.90–2.24) for incident coronary artery disease (CAD) after adjusting for sociodemographic confounders. Anxiety disorder showed a similar association (HR = 2.31, 95% CI = 1.92–2.78), while patients diagnosed with both conditions had the highest CAD risk (HR = 3.85, 95% CI = 2.48–5.98). The association between depression and CAD was strongest among those with a high CAD polygenic risk score (PRSCAD), suggesting a significant genetic contribution.
An additive interaction between depression and PRSCAD was observed (relative excess risk due to interaction = 0.97, 95% CI = 0.12–1.81), whereas anxiety disorder was linked to CAD regardless of genetic predisposition. In high PRSCAD cases, depression was associated with a CAD risk HR of 2.32 (95% CI = 1.92–2.82) compared with 2.04 (95% CI = 1.60–2.61) in the low PRSCAD group. Anxiety disorder showed consistent HRs across genetic risk categories.
The investigators used Cox proportional hazard models adjusted for mediators such as smoking status, BMI, diet quality, hypertension, and C-reactive protein levels. Although these adjustments attenuated the associations, the relationships remained significant, indicating that lifestyle factors mediate some of the risks.
Lead study author Shinya Nakada, PhD, of the School of Health and Wellbeing at the University of Glasgow, and colleagues stated: "CAD genetic susceptibility contributes to the clustering of depression and CAD by modifying their associations but does not provide the full explanation. Clustering is likely to also be due, in part, to poor mental health being associated with unhealthy lifestyle choices and their downstream biomarkers which predispose to CAD."
While the study's large sample size and rigorous methodology may strengthen its findings, limitations included reliance on ICD-10 classifications, the exclusion of non-White participants, and potential residual confounding.
The findings underscored the need for targeted cardiovascular screening and interventions in patients with depression, particularly those with high genetic risk. Future research should explore the underlying biological mechanisms and the potential for personalized medicine in mitigating these risks.
No competing interests were disclosed in the study.