Cardiovascular disease is a significant contributor to the incidence of cancer, second-primary cancer, and cancer-related hospitalization

Abstract Introduction Cardiovascular diseases (CVD) are associated with an increased risk of cancer. However, the population-attributable fraction (PAF) of CVD to cancer and the association between CVD and second-primary cancer, cancer-related hospitalizations, or death weren’t described. Methods We analyzed data from 109,204 adults, free of cancer at baseline, with valid echocardiography examination between 2000-2024. Cancer, hospitalization, and mortality data were obtained from Israel's National Registries and institutional records. CVD was defined as any significant structural or clinical heart/vascular disease. This definition includes heart failure, ischemic heart disease, atrial fibrillation, valvular diseases and stroke. We used ICD9 codes to identify 2nd primary cancer. To avoid the detection of asymptomatic cancer, we implicated a 3-month blanking period at the start of the follow-up. Then, we used Cox regression and Poisson regression to assess the link between CVD and cancer incidence, hospitalizations, and death and to adjust for age, sex, BMI, smoking, and eGFR. Results During a median follow-up of 6.0 ± 4.4 years, 4441 (4%) patients developed cancer; of them, 192 patients developed 2nd primary cancer. CVD was associated with an increased multivariable-adjusted risk of cancer (HR=1.53, 95%CI: 1.43-1.63). Moreover, CVD contributed 13% of the PAF for cancer, second only to aging and smoking (Figure 1A). CVD was also associated with a 10% higher incidence of second primary cancer (IRR=1.10, 95%CI: 1.04-1.15, Figure 1B), which is the development of another cancer type. Furthermore, CVD was also associated with a 2-fold increase in cancer-related hospitalizations in patients with cancer (1.64 vs 3.83 hospitalizations per year, IRR=2.05, 95%CI: 1.86-2.26, p<0.001, Figure 1C). Finally, we used multivariable-adjusted interaction analysis to assess the link between CVD, cancer, and mortality. We found a significant interaction between CVD and cancer, indicating that the increased risk of death associated with cancer twice fold in patients with CVD (HR=2.05, 95%CI: 1.85-2.23, p<0.001). Using the Kaplan-Meier method, we demonstrated that patients with concomitant CVD and cancer suffer from worse prognoses compared to cancer patients without CVD (Figure 1D). Conclusion We show, for the first time, that CVD is a major contributor to the burden of cancer. CVD was linked to a higher risk of cancer, second-primary cancer, a high population-attributable fraction for cancer, more cancer-related hospitalization, and increased mortality. Recognizing this association may enhance cancer prevention, early diagnosis, and treatment for patients with CVD.