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

Authors:
Shing Fung LeeDepartment of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, China;
Department of Clinical Oncology, Queen Mary Hospital, Hong Kong West Cluster, Hospital Authority, Hong Kong, China;
Department of Radiation Oncology, National University Cancer Institute, Singapore;

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Pui Lam YipDepartment of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, China;

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Balamurugan A. VellayappanDepartment of Radiation Oncology, National University Cancer Institute, Singapore;

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Cheng Ean CheeDepartment of Haematology-Oncology, National University Cancer Institute, Singapore;

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Lea Choung WongDepartment of Radiation Oncology, National University Cancer Institute, Singapore;

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Eric Yuk-Fai WanCentre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;
Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, Sha Tin, Hong Kong, China;
Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;

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Esther Wai-Yin ChanCentre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;
Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, Sha Tin, Hong Kong, China;
The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, China;
Department of Pharmacy, University of Hong Kong–Shenzhen Hospital, Shenzhen, China;

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Chak-Fei LeeDepartment of Pharmacy, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, China;
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China;

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Francis Ann-Shing LeeDepartment of Clinical Oncology, Tuen Mun Hospital, New Territories West Cluster, Hospital Authority, Hong Kong, China;

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Miguel Angel Luque-FernandezDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom;
Inequalities in Cancer Outcomes Network, London School of Hygiene and Tropical Medicine, London, United Kingdom;
Department of Non-Communicable Disease and Cancer Epidemiology, Instituto de Investigacion Biosanitaria de Granada, Granada, Spain;
Cancer Registry of Granada, Andalusian School of Public Health, Granada, Spain; and
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBER of Epidemiology and Public Health, CIBERESP), Madrid, Spain.

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 PhD, MSc, MPH

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 fluoropyrimidine-based 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 fluoropyrimidine-based 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.

Submitted March 17, 2022; final revision received June 4, 2022; accepted for publication June 6, 2022.

Author contributions: Conceptualization: S.F. Lee. Methodology: S.F. Lee, Luque-Fernandez. Data acquisition: S.F. Lee, Luque-Fernandez. Formal analysis: S.F. Lee, Luque-Fernandez. Data interpretation: All authors. Writing—original draft: All authors. Writing—review & editing: All authors. Supervision: F.A.S. Lee, Luque-Fernandez. Project administration: F.A.S. Lee, Luque-Fernandez.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this article was supported by El Instituto de Salud Carlos III under award number CP17/00206-EU-FEDER (M.A. Luque-Fernandez).

Correspondence: Miguel Angel Luque-Fernandez, PhD, MSc, MPH, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, Room 257, London, WC1E 7HT, United Kingdom. Email: miguel-angel.luque@lshtm.ac.uk

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