The role of genetic predisposition in cardiovascular risk after cancer diagnosis: a matched cohort study of the UK Biobank

Background Evidence is scarce regarding the potential modifying role of disease susceptibility on the association between a prior cancer diagnosis and cardiovascular disease (CVD). Methods We conducted a matched cohort study of UK Biobank including 78,860 individuals with a cancer diagnosis between January 1997 and January 2020, and 394,300 birth year and sex individually matched unexposed individuals. We used Cox model to assess the subsequent relative risk of CVD, which was further stratified by individual genetic predisposition. Results During nearly 23 years of follow-up, an elevated risk of CVD was constantly observed among cancer patients, compared to their matched unexposed individuals. Such excess risk was most pronounced (hazard ratio [HR] = 5.28, 95% confidence interval [CI] 4.90-5.69) within 3 months after a cancer diagnosis, which then decreased rapidly and stabilised for >6 months (HR = 1.22, 95% CI 1.19-1.24). For all the studied time periods, stratification analyses by both levels of polygenic risk score for CVD and by family history of CVD revealed higher estimates among individuals with lower genetic risk predisposition. Conclusions Our findings suggest that patients with a recent cancer diagnosis were at an increased risk of multiple types of CVD and the excess CVD risk was higher among individuals with lower genetic susceptibility to CVD, highlighting a general need for enhanced psychological assistance and clinical surveillance of CVD among newly diagnosed cancer patients.