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

Abstract

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.

Fig. 1

Flowchart of study selection process for meta-analysis.

Fig. 2. The Mendelian randomization (MR) study design.

I. IVs directly affected exposure. II. IVs were not related to any confounders. III. IVs influenced the risk of outcomes only through exposure, not through other pathways. IVs instrumental variables, SNP single nucleotide polymorphisms, CVD cardiovascular disease, CAD coronary artery disease, MI myocardial infarction, HF heart failure, MDD major depressive disorder.

Fig. 3. Meta-analyses of the prevalence of depression and anxiety in CVD patients.

A Prevalence of depression in patients with CVD. B Prevalence of anxiety in patients with CVD. ACHD adult congenital heart disease, ACS acute coronary syndrome, ACS/SA acute coronary syndrome/stable angina pectoris, AP angina pectoris, CAD coronary artery disease, CHD coronary heart disease, CVD cardiovascular disease, HF heart failure, CHF chronic heart failure, IHD ischemic heart disease, MI myocardial infarction, PCI percutaneous coronary intervention, CI confidence interval.

Fig. 4. Forest plot of hazard ratio of depression with all-cause mortality.

ACHD adult congenital heart disease, ACS acute coronary syndrome, ACS/SA acute coronary syndrome/stable angina pectoris, AP angina pectoris, CAD coronary artery disease, CHD coronary heart disease, CVD cardiovascular disease, HF heart failure, HR hazard ratio, IHD ischemic heart disease, MI myocardial infarction, PCI percutaneous coronary intervention, CI confidence interval.

Fig. 5. Results of MR analyses.

Causal effects were estimated using primary analysis (IVW), MR-Egger, and weighted median. CVD cardiovascular diseases, MDD major depressive disorder, SNPs single nucleotide polymorphisms, IVW inverse variance weighted, CI confidence interval, OR odds ratio. A The forest plot shows the causal relationship between CVD and MDD, anxiety. IVW method indicated no significant association between CVD and MDD phenotypes (OR = 1.003, 95% CI = 0.960–1.047, P = 0.905), CVD and anxiety phenotypes (OR = 1.187, 95% CI = 0.942–1.495, P = 0.146), MR-Egger and weighted median method also showed consistent results. B The forest plot shows the causal association between various CVDs and depression phenotypes. IVW method results revealed significant associations between CAD and MDD (OR = 1.021, 95% CI: 1.001–1.041, P = 0.035), myocardial infarction and depression (OR = 1.038, 95% CI: 1.005–1.072, P = 0.022), heart failure and MDD (OR = 1.064, 95%CI: 1.003–1.129, P = 0.039), and hypertension and depression (OR = 1.517, 95% CI: 1.210–1.903, P < 0.001). C The forest plot of reverse causal effects of depression and anxiety phenotypes on various CVDs. IVW method results revealed significant associations between depression and CAD (OR = 1.183, 95% CI: 1.057–1.325, P = 0.004), depression and myocardial infarction (OR = 1.214, 95% CI: 1.091–1.351, P < 0.001), MDD and CVD (OR = 1.168, 95% CI: 1.073–1.270, P < 0.001), MDD and CAD (OR = 1.337, 95% CI: 1.222–1.462, P < 0.001), MDD and myocardial infarction (OR = 1.281, 95% CI: 1.142–1.438, P < 0.001), MDD and heart failure (OR = 1.107, 95% CI: 1.025–1.196, P = 0.010), MDD and hypertension (OR = 1.013, 95% CI: 1.001–1.025, P = 0.035),and anxiety and heart failure (OR = 1.008, 95% CI: 1.000–1.016, P = 0.048).