Incident Cardiovascular Diseases among Survivors of High-Risk Stage II–III Colorectal Cancer: A Cluster-Wide Cohort Study

Abstract

Background: The incidence and survival of colorectal cancer (CRC) are increasing. There is an increasing number of long-term survivors, many of whom are elderly and have comorbidities. We conducted a population-based study in Hong Kong to assess the long-term cardiovascular disease (CVD) incidence associated with adjuvant fluoropyrimidinebased chemotherapy among CRC survivors. Patients and Methods: Using the population-based electronic medical database of Hong Kong, we identified adults who were diagnosed with high-risk stage II–III CRC and treated with radical surgery followed by adjuvant fluoropyrimidinebased chemotherapy between 2010 and 2019. We evaluated the cause-specific cumulative incidence of CVD (including ischemic heart disease, heart failure, cardiomyopathy, and stroke) using the flexible parametric competing risk modeling framework. The control group without a history of CVD was selected from among a noncancer random sample from primary care clinics in the same geographic area. Results: We analyzed 1,037 treated patients with CRC and 5,078 noncancer controls. The adjusted cause-specific hazard ratio (HR) for CVD in the cancer cohort compared with the control group was 2.11 (95% CI, 1.39–3.20). The 1-, 5-, and 10-year cause-specific cumulative incidences were 2.0%, 4.5%, and 5.4% in the cancer cohort versus 1.2%, 3.0%, and 3.8% in the control group, respectively. Age at cancer diagnosis (HR per 5-year increase, 1.16; 95% CI, 1.08–1.24), male sex (HR, 1.40; 95% CI, 1.06–1.86), comorbidity (HR, 1.88; 95% CI, 1.36–2.61 for 1 comorbidity vs none, and HR, 6.61; 95% CI, 4.55–9.60 for $2 comorbidities vs none), diabetes (HR, 1.38; 95% CI, 1.04–1.84), hypertension (HR, 3.27; 95% CI, 2.39–4.50), and dyslipidemia/hyperlipidemia (HR, 2.53; 95% CI, 1.68–3.81) were associated with incident CVD. Conclusions: Exposure to adjuvant fluoropyrimidine-based chemotherapy was associated with an increased risk of CVD among survivors of high-risk stage II–III CRC. Cardiovascular risk monitoring of this group throughout cancer survivorship is advisable.