Risk of Cardiovascular Disease Mortality in Patients With Diagnosed Cancer and Associated Genetic and Proteomic Mechanisms: A UK Biobank-Based Cohort Study.
BACKGROUND: Previous studies have identified a link between cancer and cardiovascular disease; however, the underlying genetic and proteomic mechanisms remain unclear. Therefore, this study aimed to investigate the association between cancer diagnosis and cardiovascular mortality and to explore the potential mechanisms involved. METHODS: A total of 379 944 participants without cardiovascular disease at baseline, including 65 047 individuals with cancer, were recruited from the UK Biobank database. The primary end point was cardiovascular death. Multivariate Cox regression was performed to evaluate the risk of cardiovascular death in populations with and without cancer. Genome-wide association studies, phenome-wide association studies, and proteomic analyses were applied to investigate the underlying genetic and proteomic mechanisms. RESULTS: Multivariate Cox regression analysis showed an increased risk of cardiovascular death in the group with cancer (hazard ratio, 1.50 [95% CI, 1.40-1.61]) after multivariable adjustment. Proteomic analysis confirmed a strong association between cancer and cardiovascular disease, primarily involving pathways related to complement and coagulation cascades, and various inflammatory processes. In contrast, genome-wide association studies and phenome-wide association studies revealed only a limited number of shared genetic variations between cancer and cardiovascular conditions, such as hypertension and cardiac dysrhythmias. CONCLUSIONS: Cardiovascular risk is increased in patients with cancer and may be related to altered expression of inflammation- and coagulation-related proteins. In clinical practice, it is recommended to emphasize the management of endocrine, kidney, and inflammation-related risk factors in the population with cancer.