Association Between Myocardial Infarction and Depression: Bidirectional Links and Shared Risk Pathways—A Systematic Review and Meta-Analysis

Abstract Aims To examine the bidirectional association between myocardial infarction (MI) and depression and to summarize shared comorbidities and cardiovascular risk factors underlying their co-occurrence. Methods PubMed, Embase, and PsycINFO were searched from inception to 31 December 2025 for prospective cohort and longitudinal studies reporting time-to-event estimates for either direction of the MI–depression association. Random-effects meta-analyses were used to pool adjusted hazard ratios (HRs), with heterogeneity assessed using the I2 statistic. Study quality was evaluated using the Newcastle–Ottawa Scale. Subgroup analyses by sex and age and sensitivity analyses restricted to high-quality studies and studies with only clinically diagnosed depression were performed. Antidepressant treatment class was examined exploratorily, and shared comorbidities and cardiovascular risk factors were synthesized descriptively. Results Nine population-based cohort studies were included. Meta-analysis of two studies showed that MI was associated with an increased risk of subsequent depression (pooled adjusted hazard ratio HR 1.41, 95% confidence interval CI 1.24–1.61; I2 = 0%). Eight studies examining depression as the exposure demonstrated an increased risk of incident MI (pooled adjusted HR 1.42, 95% CI 1.29–1.57), with substantial heterogeneity (I2 = 84.7%). Stratified estimates from individual studies suggested stronger relative associations among younger individuals and sex-specific differences according to the direction of the association. Sparse evidence indicated that tricyclic antidepressant use was associated with a higher observed risk of MI, whereas selective serotonin reuptake inhibitors were not. Cardiometabolic and mental comorbidities, including diabetes, hypertension, dyslipidaemia, coronary heart disease, stroke, anxiety, and post-traumatic stress disorder, alongside chronic kidney disease, were commonly reported across both temporal directions. Conclusions MI and depression show bidirectional associations, with each condition conferring an increased risk for the other. These associations are observed alongside demographic differences and shared cardiometabolic and mental comorbidities, stressing the importance of integrated cardiovascular and mental health assessment; however, these findings should be interpreted cautiously given the limited available evidence.