Article Impact Level: HIGH Data Quality: STRONG Summary of JACC: CardioOncology, 7(5), 514–517. https://doi.org/10.1016/j.jaccao.2025.05.016 Dr. Jessie M. Dalman et al.
Points
- Large-scale observational studies confirm that atherosclerotic events like myocardial infarction significantly increase the risk of developing subsequent malignancies and are associated with worse prognoses.
- Ischemic injury from cardiovascular disease causes epigenetic reprogramming of bone marrow stem cells, leading to a state of premature immune aging known as inflammaging that favors tumor growth.
- This process creates an immunosuppressive tumor microenvironment by increasing the number of myeloid-derived suppressor cells and regulatory T cells, while reducing the effectiveness of anti-tumor lymphocytes.
- Specific molecular pathways implicated in this process include cardiac-secreted factors, such as serpinA3 and nerve growth factor, which activate pro-proliferative signaling pathways, including the PI3K-AKT pathway.
- These findings underscore the need for enhanced cancer surveillance in CVD patients and highlight potential therapies like anti-inflammatory agents to disrupt this pro-tumorigenic connection.
Summary
Observational cohort studies have established a significant association between atherosclerotic cardiovascular disease (CVD) and subsequent cancer development. An analysis of over 2 million patients found that a diagnosis of myocardial infarction (MI) increased the likelihood of developing malignancies. At the same time, a separate study of 589 individuals with acute coronary syndrome noted a cancer incidence rate three times higher than expected in the general population. Furthermore, data from over 21,000 patients demonstrated that atherosclerotic CVD is independently associated with an increased probability of metastatic disease at the time of cancer diagnosis. These findings suggest a direct pro-tumorigenic effect of CVD, independent of shared risk factors like age, smoking, or obesity, prompting investigation into the underlying biological mechanisms.
Preclinical studies using mouse models have elucidated key mechanisms driving this connection. Post-MI heart failure was shown to cause a >2-fold increase in intestinal tumor burden, an effect mediated by cardiac-secreted factors like serpinA3, which activates AKT signaling. Ischemic events, including both MI and peripheral artery ligation, were found to accelerate breast cancer growth by double. This is driven by the epigenetic reprogramming of hematopoietic progenitor cells in the bone marrow toward a myeloid-biased, immunosuppressive phenotype consistent with inflammaging. This systemic alteration, which is transmissible via bone marrow transplantation, results in an increased circulation of Ly6Chigh monocytes, leading to the accumulation of myeloid-derived suppressor cells and regulatory T cells within the tumor microenvironment.
These mechanistic insights highlight dysfunctional myelopoiesis and chronic inflammation as central to the pro-tumorigenic state induced by atherosclerotic CVD. Specific signaling pathways, including the PI3K-AKT pathway, are enriched in tumors following myocardial infarction (MI), potentially driven by elevated levels of nerve growth factor (NGF). These findings present opportunities for therapeutic intervention and augmented clinical care. Anti-inflammatory agents like canakinumab, which reduced fatal cancer incidence by 77% in patients with a prior MI, may disrupt this pathological crosstalk. This evidence supports enhancing cancer surveillance protocols for patients with a history of ischemic events and exploring therapies that target shared inflammatory pathways.
Link to the article: https://www.jacc.org/doi/10.1016/j.jaccao.2025.05.016
References Dalman, J. M., & Moore, K. J. (2025). Cancer development in atherosclerotic cardiovascular disease. JACC: CardioOncology, 7(5), 514–517. https://doi.org/10.1016/j.jaccao.2025.05.016
