Molecular basis of coronary artery disease-malignancy comorbidity: inflammation, immunometabolism, thrombosis, and cardio-oncology translation.

Coronary artery disease (CAD) and malignancy frequently coexist in aging populations and share multiple risk factors, including smoking, obesity, diabetes, dyslipidemia, chronic inflammation, and metabolic dysfunction. However, increasing evidence suggests that CAD-malignancy comorbidity cannot be fully explained by epidemiological coincidence alone, although its causal direction remains difficult to establish because of shared risk factors, surveillance bias, reverse causality, cancer stage, and treatment exposure. Instead, convergent inflammatory, metabolic, thrombotic, and immune mechanisms may contribute to the observed clinical overlap. This review summarizes recent evidence linking CAD and cancer through chronic systemic inflammation, clonal hematopoiesis, inflammasome activation, immunometabolic remodeling, endothelial dysfunction, platelet activation, neutrophil extracellular trap formation, coagulation, and immune checkpoint disruption. Particular attention is given to clonal hematopoiesis as a molecular bridge between malignant predisposition and atherosclerosis, macrophage and T-cell immunometabolism as shared immune programs, and thromboinflammation as a mechanism connecting cancer-associated thrombosis with coronary vascular events. We further discuss cardio-oncology translation, including immune checkpoint inhibitor-related cardiovascular toxicity, CHIP-guided anti-inflammatory prevention, antiplatelet and antithrombotic strategies, endothelial-targeted interventions, and immune checkpoint-aware cardiovascular monitoring. Understanding these shared pathways may help move cardio-oncology beyond the management of therapy-induced cardiotoxicity toward mechanism-guided prevention and treatment of inflammatory, thrombotic, and immune mechanisms that jointly promote CAD progression and cancer development.