Cancer risk subsequent to cardiovascular disease: a prospective population-based study and meta-analysis

Previous preclinical studies have revealed the biological links between cardiovascular diseases (CVD) and cancer. However, population-based evidence remained inconclusive.

We assessed cancer incidence among individuals with and without CVD condition in a prospective cohort from the UK Biobank (UKB). Multivariable Cox regression and competing risk models were fitted to estimate hazard ratios (HR). A systematic literature search was conducted in Medline, Embase and Cochrane Library databases to identify published population-based cohort studies (last updated on 1 October 2023) investigating the associations between CVD status and subsequent cancer risk. Random-effects meta-analysis was employed to pool relative effect estimates reported by eligible cohorts. Subgroup and sensitivity analyses were conducted to evaluate the associations across various CVD and cancer subtypes.

For the cohort study in the UKB, after a median follow-up of 11.58 years, a total of 18,471 and 66,891 cancer cases occurred among 94,845 CVD patients and 368,695 non-CVD individuals (Incidence rate: 25.62 vs. 15.41 per 1000 person-years). Individuals with prior CVD exhibited higher overall cancer risk (HR 1.14, 95% CI 1.12-1.17, p < 0.001), and we observed consistently higher cancer risk after adjusting for competing risk from non-cancer deaths. The effect size of CVD on cancer risk was greater among younger individuals (< 65 years) than those ≥ 65 years (p for interaction < 0.001). The meta-analysis included 47 population-based cohort studies where a total of 1.49 million cancer cases were documented among over 45 million participants (9.49 million CVD patients). A 13% higher risk of overall cancer was observed among individuals with prior CVD (pooled RR 1.13, 95% CI 1.11-1.15, p < 0.001). The associations remained significant between various CVD subtypes and cancer risk at multiple sites.

Our study identified a significantly higher cancer risk among individuals with CVD conditions compared with the non-CVD population, underpinning the need for continued cancer surveillance among CVD patients and further exploration of the possible etiological relation between CVD and cancer.