Abstract

Background: While heart diseases are associated with an increased incidence of cancer, the association between cardiovascular diseases (CVD) and cancer metastasis, the primary determinant of cancer prognosis, has never been studied. We aimed to determine the association between CVD and cancer metastasis. Methods: We evaluated 21,952 self-referred adults, free of cancer and CVD (ischemic heart disease/stroke) at baseline, who were screened in our preventive healthcare. Next, we implicated a 1-year blanking period at the start of the follow-up. Then, a Cox regression model with CVD as a time-varying covariate was used to evaluate the association between CVD and metastatic cancer. Finally, we implicated the same models in evaluating the risk of young (ages Q1-3) and old adults (ages Q4). Results: During a median follow-up of 7 years (IQR 3-13 years), 1359 subjects developed CVD, and 920 subjects developed metastatic cancer. Subjects who developed CVD were 71% more likely to develop cancer metastasis by a univariate model (HR= 1.33, 95% CI 1.05-1.69, p=0.02). The risk persisted after adjustment for risk factors by a multivariate model (95% CI 1.33-2.20, p<0.001), as well as landmark analysis (HR=1.84 95%CI 1.42-2.34, p<0.001) ( Fig-1) . The association of CVD with the risk of metastatic cancer was age-dependent (p for interaction = 0.035): significant among younger adults (43±6 years, HR=1.57,95% CI 1.02-2.42, p=0.040), compared with older adults (60±6 years, HR=1.12, 95% CI 0.80-1.56, p=0.522). Notably, CVD emerged as a risk factor for metastatic cancer in younger adults despite a lower rate of common risk factors. Conclusions: We show, for the first time, that cardiovascular diseases are associated with an increased and independent risk of cancer metastasis. The risk is age-dependent and more significant among young adults. Understanding this association could promote early diagnosis, risk stratification, and better treatment of cardiovascular diseases and cancer.

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