Causal Relationships between Anxiety, Depression, Their Influencing Factors, and Chronic Heart Failure: A Mendelian Randomization Study

Background: Chronic heart failure (CHF) is a major cardiovascular disease linked to mental health, lifestyle, and socioeconomic factors. This study aims to assess the causal relationships between genetically predicted anxiety, depression, their influencing factors, and CHF risk. Methods: A two-sample bidirectional mendelian randomization (MR) analysis was conducted using genetic variants from large-scale GWAS as instrumental variables. Exposures included genetically predicted anxiety, depression, C-reactive protein (CRP), interleukin-6 (IL-6), smoking, physical activity, education level, and socioeconomic factors (number in household, and number of vehicles in a household). Causal effects were assessed using inverse variance weighted (IVW), MR-Egger, Simple mode, Weighted median, and Weighted mode methods while addressing pleiotropy and confounding. Results: The MR analysis identified CRP and smoking as significant causal risk factors for CHF, with CRP (odds ratio (OR) = 1.089, 95% confidence interval (CI): 1.024–1.157, p = 0.007) supporting an inflammatory role in CHF pathogenesis and smoking (OR = 1.250, 95% CI: 1.045–1.495, p = 0.015) reinforcing its established cardiovascular risks. In contrast, higher education level (OR = 0.713, 95% CI: 0.518–0.981, p = 0.038) and number of vehicles in a household (OR = 0.587, 95% CI: 0.351–0.982, p = 0.042) were protective against CHF. No significant causal associations were found between CHF and genetically predicted anxiety, depression, IL-6 levels, physical activity, or household size (p > 0.05). Additionally, reverse MR analysis found no evidence that CHF causally influences these factors through genetic pathways. Conclusion: These findings emphasize the importance of targeting modifiable risk factors (CRP and smoking) for CHF prevention and suggest that education and vehicle ownership may improve CHF outcomes, highlighting the need for further research on non-genetic pathways linking mental health and CHF.