Cardiovascular disease as a driver of tumor development: epidemiological, mechanistic and bioinformatic insights

In recent years, the field of Cardio-Oncology has expanded beyond its traditional focus on cancer therapy–related cardiotoxicity. Growing evidence now supports a bidirectional relationship between cardiovascular disease (CVD) and cancer, in which CVD may promote tumor progression. Multiple epidemiological studies across diverse CVD phenotypes—including atherosclerosis, hypertension, myocardial infarction, atrial fibrillation and heart failure (HF)—point towards higher cancer incidence and mortality, extending beyond shared risk factors and pathophysiological pathways. Furthermore, animal experimentation has provided mechanistic clues linking cardiac injury to exacerbated cancer progression. Proposed mechanisms include cardiac secretion of tumor‑potentiating proteins and small extracellular vesicles, immune reprogramming and HF-associated gut microbiome dysbiosis. Notably, the impact of CVD on tumor progression appears cancer‑type-specific and may vary across tumor models, underscoring biological heterogeneity in heart-to-tumor crosstalk. In this review, we provide an overview of epidemiological and mechanistic evidence linking CVD to increased tumor growth. Additionally, we performed an analysis of literature-reported chronic HF biomarkers and their association with cancer. This analysis identified a subset of HF biomarkers with strong associations across multiple cancer types, highlighting potential molecular mediators of CVD-induced oncogenic signaling. Collectively, current evidence from epidemiological, experimental and computational data indicates a complex biological and potentially causal relationship between CVD and cancer, involving multiple mechanisms. Advancing mechanistic understanding may improve oncological risk stratification in CVD populations, guide the development of targeted strategies to disrupt heart-to-tumor signaling and strengthen the foundation for integrated Cardio-Oncology care.