Increased incidence of cancer metastasis in young patients with ischaemic heart disease

Abstract Background Heart disease has been linked to an increased risk of developing certain types of cancer. However, while cancer metastasis is the primary determinant of cancer prognosis, the association between heart disease and cancer metastasis has never been studied in humans. Methods We evaluated 22,057 self-referred adults, free of cancer and IHD at baseline, who were screened in preventive healthcare as private individuals. To eliminate the cases of silent cancer, we implicated a one-year blanking period at the start of the follow-up. Cancer and mortality data were available for all subjects from national registries. Then, multivariable Cox regression model with IHD as a time-dependent covariate was used to evaluate the association of IHD with metastatic cancer during follow-up. Finally, we implicated the same models in evaluating the differences in risk between young (age<55) and old adults. Results During a median follow-up of 6.5 years (Interquartile range 3-13 years), 913 subjects developed IHD and 929 subjects developed metastatic cancer. Compared with subjected who did not develop IHD during follow-up, subjects who developed IHD during follow-up were 64% more likely to develop metastatic cancer during follow-up, in a univariate model (95% CI 1.15-2.36, p=0.0006). Multivariable analysis with adjustment for common risk factors yielded consistent results such that IHD was associated with 50% increased risk of metastatic cancer (Fig-A, p=0.005). Moreover, IHD was associated with poor survival of cancer patients with and without metastasis (HR=1.75 and 1.65, p<0.001 for both). Subgroup analysis demonstrated that the association of IHD with the risk of metastatic cancer was age-dependent: the association was more significant among younger subjects below 55 years of age (Fig-B, n=17,433, n(IHD)=433, HR=2.24, p=0.011), compared with older subjects (n=4624, n(IHD)=480, HR=0.91, p=0.711; p for interaction = 0.085). Notably, IHD emerged as a risk factor for metastatic cancer in younger adults (<55) despite lower rate of cardiovascular risk factors. Conclusions We show, for the first time, that ischaemic heart disease is associated with increased and independent risk of metastatic cancer. Furthermore, we demonstrated that the risk is age-dependent and more pronounced among patients younger than 55. Understanding this relationship could lead to advances in cardiovascular and cancer treatment and could ultimately help to improve patient outcomes.