Atherosclerotic Cardiovascular Disease and Cancer are Bidirectionally Linked by Shared Immune Mechanisms

Atherosclerotic cardiovascular disease (ASCVD) and cancer are leading causes of morbidity and mortality, traditionally viewed as distinct conditions with overlapping risk factors. However, emerging evidence suggests a deeper, mechanistic interplay. Conventional treatments for one often exacerbate the other, highlighting a critical gap in understanding their shared pathogenesis. This review addresses the need to integrate these fields, exploring how a chronic inflammatory milieu, driven by factors like aging and clonal hematopoiesis of indeterminate potential (CHIP), orchestrates immune reprogramming that fuels both diseases. Understanding this interconnectedness is crucial for developing more holistic therapeutic strategies.

This comprehensive review integrated emerging mechanistic and clinical evidence to establish a unified view of ASCVD and cancer as immune-driven diseases. The authors synthesized findings across various studies, focusing on shared immune mechanisms, bidirectional axes of interaction, and the role of chronic inflammation. They examined how common exposures and aging contribute to a pro-inflammatory state, influencing both pathologies. The review specifically analyzed the impact of cancer therapies on cardiovascular injury (forward axis) and how cardiovascular injury states promote cancer (reverse axis), alongside the role of immune checkpoint pathways and inflammatory cytokines in both disease contexts.

The review elucidated a profound, bidirectional relationship between ASCVD and cancer, driven by shared immune mechanisms. It highlighted how a chronic inflammatory milieu, often amplified by CHIP-associated clones, reprograms both myeloid and lymphoid immune compartments. > A key finding is the recognition of a "forward cardio-oncology axis" where cancer therapies (chemotherapies, radiation, immune checkpoint inhibitors) induce cardiovascular injury, manifesting as cardiomyopathy, accelerated atherosclerosis, and immune-mediated myocarditis. Conversely, a "reverse axis" demonstrates that cardiovascular injury states (myocardial infarction, ischemia, heart failure) actively promote cancer initiation and progression through hematopoietic remodeling, extracellular vesicle-mediated communication, cardiac-derived factors, and immunosuppressive myeloid bias. At the tissue level, immune checkpoint pathways including PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3 form spatially organized regulatory networks within atherosclerotic plaques. Their therapeutic perturbation, while restoring T cell activity, may disrupt local immune homeostasis and promote plaque instability. Furthermore, inflammatory cytokines such as IL-1β, IL-6, and TNF-α provide a mechanistic bridge linking atherogenesis with tumor immune evasion, reinforcing the concept of a unified, immune-driven pathology.