Anger, sadness, and the biology of myocardial infarction: reframing emotion as a driver of atherothrombosis - a literature review.

BACKGROUND: Negative emotions, including anger, depressive symptoms, and chronic psychosocial stress, are increasingly linked to residual atherosclerotic cardiovascular disease (ASCVD) risk through neuroautonomic, inflammatory, endothelial, and thrombotic pathways. OBJECTIVES: To synthesize epidemiologic, mechanistic, and interventional evidence relating anger and depressive affect to myocardial infarction (MI) risk, and to outline clinically actionable translational opportunities. METHODS: We conducted a literature review of adult human studies identified through searches of MEDLINE/PubMed, Embase, PsycINFO, CINAHL, Web of Science, and the Cochrane Library from January 1990 to October 2025. After screening 1180 titles/abstracts and reviewing 146 full-text reports, 70 sources were included and narratively synthesized. RESULTS: Across cohorts and meta-analyses, depressive symptoms or major depressive disorder are associated with higher incident CHD/MI risk after multivariable adjustment, though effect sizes vary and residual confounding is possible. Case-crossover studies show a short-term increase in MI risk following intense anger episodes. Mechanistic evidence supports plausible pathways including autonomic surges, HPA-axis dysregulation, endothelial dysfunction, inflammatory signaling (e.g., IL-6/NLRP3), and catecholamine-related thrombogenicity. Interventions-β-blockers, SSRIs, cognitive behavioral therapy (CBT), and mindfulness-based stress reduction (MBSR)- improve emotional symptoms and selected surrogate vascular/inflammatory measures; evidence for reduction in hard cardiovascular outcomes remains limited and mixed. CONCLUSION: Negative emotions are consistently associated with MI risk and align with biologically plausible mechanisms overlapping with residual inflammatory and autonomic risk. Integrating validated emotion screening and scalable interventions into prevention and rehabilitation warrants rigorous evaluation with equity- and privacy-centered implementation.