Atherosclerotic Cardiovascular Disease and Cancer

Abstract

Atherosclerotic cardiovascular disease (ASCVD) and cancer are increasingly recognized as interconnected diseases linked by shared immune mechanisms rather than merely overlapping risk factors. Common exposures such as smoking, obesity, diabetes, and dyslipidemia, together with aging and clonal hematopoiesis of indeterminate potential (CHIP), establish a chronic inflammatory milieu that drives both pathologies through coordinated reprogramming of myeloid and lymphoid compartments. Within this framework, a forward cardio-oncology axis is increasingly recognized, in which cancer therapies including chemotherapies, radiation, and immune checkpoint inhibitors induce cardiovascular injury, manifesting as cardiomyopathy, accelerated atherosclerosis, and immune-mediated myocarditis. Complementing this, a reverse axis has emerged in which cardiovascular injury states such as myocardial infarction, ischemia, and 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 restores T cell activity but may disrupt local immune homeostasis and promote plaque instability. In parallel, inflammatory cytokines such as IL-1β, IL-6, and TNF-α, often amplified by CHIP-associated clones, provide a mechanistic bridge linking atherogenesis with tumor immune evasion. Together, these observations support a unified view of ASCVD and cancer as immune-driven diseases connected by bidirectional axes of interaction. This review integrates emerging mechanistic and clinical evidence and outlines how immune-based stratification and targeted modulation of inflammation may enable more precise management of patients at the intersection of cardiovascular disease and cancer.