Hallmarks of cancer in patients with heart failure: data from BIOSTAT-CHF.

Background: Within cardio-oncology, emerging epidemiologic studies have demonstrated a bi-directional relationship between heart failure (HF) and cancer. In the current study, we aimed to further explore this relationship and investigate the underlying pathophysiological pathways that connect these two disease entities.

Methods: We conducted a post-hoc analysis in which we identified 24 Gene Ontology (GO) processes associated with the hallmarks of cancer based on 92 biomarkers in 1960 patients with HF. We performed Spearman's correlations and Cox-regression analyses to evaluate associations with HF biomarkers, severity and all-cause mortality.

Results: Out of a total of 24 GO processes, 9 biological processes were significantly associated with adverse clinical outcome. Positive regulation of mononuclear cell proliferation demonstrated the highest hazard for reaching the clinical endpoint, even after adjusting for confounders: all-cause mortality HR 2.00 (95% CI 1.17-3.42), p = 0.012. In contrast, negative regulation of apoptotic process was consistently associated with a lower hazard of reaching the clinical outcome, even after adjusting for confounders: all-cause mortality HR 0.74 (95% CI 0.59-0.95), p = 0.016. All processes significantly correlated with HF biomarkers, renal function and HF severity.

Conclusions: In patients with HF, GO processes associated with hallmarks of cancer are associated with HF biomarkers, severity and all-cause mortality.