Cardiovascular diseases and depression: A meta-analysis and Mendelian randomization analysis

Depression is a common psychiatric symptom among patients with cardiovascular disease (CVD), adversely affecting their health. Despite the identification of various contributing factors, the precise mechanisms linking CVD and depression remain elusive. This study conducted a meta-analysis to investigate the association between CVD and depression. Furthermore, a bidirectional Mendelian randomization (MR) analysis was undertaken to clarify the causal relationship between the two conditions. The meta-analysis included 39 studies, encompassing 63,444 patients with CVD, 12,308 of whom were diagnosed with depression. The results revealed a significant association between CVD and depression or anxiety, with an estimated overall prevalence of depression in CVD patients of 20.8%. Subgroup analyses showed that the prevalence of depression in patients with coronary artery disease and heart failure was 19.8% and 24.7%, respectively. According to a random-effects model, depressive symptoms were linked to an increase in unadjusted all-cause mortality compared with non-depressed patients. The MR analysis, employing the inverse-variance weighted method as the primary tool for causality assessment, identified significant associations between various CVD types and depression or anxiety phenotypes. These findings underscore the significant relationship between CVD and depression or anxiety, leading to an elevated risk of all-cause mortality. Moreover, the MR analysis provides the first genetically-informed evidence suggesting that depression plays a critical role in the development and progression of certain CVD subtypes. This emphasizes the need for addressing depressive symptoms in CVD patients to prevent or reduce adverse cardiovascular outcomes.