The Dutch Cardio-Oncology cohort: Incidence of cardiovascular disease predisposes to a higher cancer mortality rate

Abstract Background Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. The relationship between the two diseases is complex and multi-factorial, with both diseases sharing risk factors and influencing each other's pathogenesis and progression. Given this interaction and the high prevalence of both CVD and cancer, it is crucial to understand the impact of CVD incidence on cancer mortality and to evaluate which CVD patients are at highest risk. This study aims to evaluate which patients with incidence cardiovascular disease have a higher risk of malignancy-related mortality, stratified for type of cardiovascular disease and compared to the general population without cardiovascular diseases. Methods We performed a national population-based cohort study with incidence CVD patients, in the Netherlands between January 2000 and December 2005. A control group was selected from the entire Dutch population using a genetic matching algorithm, which consists of the closest match for age and sex, and a propensity scores for country of birth. Both CVD and control patients were older than 18 years and did not have current diagnosis or a history of CVD and malignancies in the 5 years before inclusion. Mortality data were evaluated after data linkage of national registries from Dutch Hospital Data and Statistics Netherlands until December 2020. Cox proportional hazard models were performed to evaluate mortality risk. Results A total of 2 240 879 participants were included with a mean follow-up of 12 years (sd 7.6), of which 738 666 developed CVD. Mean age was 70.5 years (sd 14.8) for CVD patients and 66.4 years (sd 15.9) for control patients. Amongst CVD patients, 492 551 (66.7%) died within follow-up, in 90 982 (12.3%) malignacies were the primary cause. For control patients, this was 641 117 (42.7%) and 169 180 (11.3%), respectively. Correcting for follow-up time, malignancy-related mortality incidence rates per 1000 person years were 118 for patients with CVD and 84 for control patients. The hazard of malignancy-related mortality was significantly higher in CVD patients compared to control patients (HR 1.42, 95% CI 1.41 – 1.43). The patients most at risk were those with venous diseases (i.e. phlebitis, venous embolism and thrombosis; HR 2.28 95% CI (2.20 – 2.36) and peripheral artery disease (HR 1.89, 95% CI 1.81 – 1.94). The incidence rate of malignancy related mortality was highest in patients with heart failure, with an incidence of 258 per 1000 person-years. Conclusions This is the first in depth study evaluating malignancy-related mortality in patients with newly developed CVD. Results show that CVD predisposes to a higher cancer mortality rate, especially in patients with venous and peripheral artery diseases. The interaction between CVD and cancer underlines the need to develop strategies for early detection and effective management of both diseases in this population.