Atherosclerotic Cardiovascular Disease and Cancer

Figures

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  FIGURE 1. Shared risk factors linking atherosclerotic cardiovascular disease and cancer. Atherosclerotic cardiovascular disease (ASCVD) and cancer share numerous overlapping biological, environmental, and clinical risk factors that contribute to the bidirectional relationship observed in cardio‐oncology. Modifiable risk factors include obesity, diabetes mellitus, hypertension, dyslipidemia, gut dysbiosis, and adverse lifestyle or environmental exposures such as smoking, psychosocial stress, physical inactivity, and poor diet. Non‐modifiable contributors include clonal hematopoiesis of indeterminate potential (CHIP), aging, genetic predisposition, and autoimmune disease. Together, these shared determinants promote chronic inflammation, immune dysregulation, metabolic dysfunction, and tissue remodeling, creating a common pathogenic framework that increases susceptibility to both cardiovascular disease and malignancy. The convergence of these pathways highlights the need for integrated prevention and therapeutic strategies across cardiovascular and oncologic care.

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  FIGURE 2. Schematic overview of immune checkpoint interactions within the human atherosclerotic plaque microenvironment. FSCN1+CCR7+ dendritic cells (DCs) interact with multiple T‐cell subsets through canonical inhibitory checkpoint pathways, including CD86–CTLA‐4, LGALS3–LAG3, and PD‐L1–PD‐1 signaling. These interactions modulate T‐cell activation, exhaustion, and regulatory function within plaques, influencing local inflammation and immune homeostasis. CD4+ T cells, CD8+ T cells, and double‐positive (DP) T cells are key cellular targets of checkpoint‐mediated regulation. Metabolic context alters this checkpoint landscape. During lipid lowering, reduced expression of CD86, LGALS3, and PD‐L1 is associated with weaker inhibitory signaling, diminished regulatory T‐cell suppression, and partial reversal of CD8+ T‐cell exhaustion. In contrast, type 2 diabetes enhances checkpoint signaling through increased CD86 expression, AGE‐driven LGALS3 induction, and elevated PD‐L1 expression on macrophages and DCs.

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  FIGURE 3. Schematic illustration of the reciprocal relationship between cancer and atherosclerotic cardiovascular disease (ASCVD). In the traditional cardio‐oncology paradigm, tumors promote cardiovascular pathology through the release of circulating tumor‐derived factors (tumor secretome) and through cardiovascular toxicities associated with cancer therapies, including chemotherapy, radiation, and immune checkpoint inhibitors. These processes contribute to vascular inflammation, endothelial dysfunction, and accelerated atherosclerosis. Conversely, in the emerging field of reverse cardio‐oncology, cardiovascular disease influences cancer progression. Myocardial infarction (MI) and heart failure (HF) induce systemic alterations including hematopoietic remodeling in the bone marrow and release of cardiac‐derived secreted factors that reshape immune responses and the tumor microenvironment, thereby promoting tumor growth and metastasis. Together, these bidirectional interactions highlight the complex crosstalk between cardiovascular disease and cancer and underscore the need for integrated mechanistic and therapeutic approaches across both disciplines.