Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases

Abstract

Background: The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps.

Methods: For this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time.

Findings: Between Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57-1·89) in patients after prostate cancer to 9·72 (5·50-17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66-2·25, with non-Hodgkin lymphoma; 1·77, 1·50-2·09, with leukaemia; and 3·29, 2·59-4·18, with multiple myeloma), oesophageal (1·96, 1·46-2·64), lung (1·82, 1·52-2·17) kidney (1·73, 1·38-2·17) and ovarian (1·59, 1·19-2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy.

Interpretation: Survivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites.

Funding: Wellcome Trust and Royal Society.

Figure 1

Absolute and relative risks of cardiovascular disease outcomes in cancer survivors compared with those of general population controls Cancer types or sites are ordered according to corresponding codes from the International Classification of Diseases, version 10 (ICD-10). Cancer sites without data had too few events for estimation. Arrowheads represent a CI limit lower than 0·5 or higher than 12. HR=hazard ratio. IR=incidence per 1000 patient-years. CS=cancer survivors. GPC=general population controls. NHL=Non-Hodgkin lymphoma.

Figure 1

Absolute and relative risks of cardiovascular disease outcomes in cancer survivors compared with those of general population controls Cancer types or sites are ordered according to corresponding codes from the International Classification of Diseases, version 10 (ICD-10). Cancer sites without data had too few events for estimation. Arrowheads represent a CI limit lower than 0·5 or higher than 12. HR=hazard ratio. IR=incidence per 1000 patient-years. CS=cancer survivors. GPC=general population controls. NHL=Non-Hodgkin lymphoma.

Figure 2

Study cohort profile for primary analysis Where multiple exclusion reasons are listed, some patients met more than one listed criteria. BMI=body-mass index. IMD=Index of multiple deprivation. *Index date was 1 year after date of diagnosis.

Figure 3

Relative risk of cardiovascular disease outcomes in cancer survivors compared with that of the general population, with effect modification (selected models) p_int=p for interaction (likelihood ratio test). CVD=cardiovascular disease. HR=hazard ratio.

Figure 4

Absolute incidence of cardiovascular disease outcomes compared with expected incidence by age group and time since diagnosis Incidence in cancer survivors and expected incidence calculated by fitting flexible parametric survival models with exposure (cancer survivor vs control), covariates, and interaction between exposure and time since diagnosis and by predicting incidence for exposed or unexposed at the mean value of covariates in cancer survivors. Cancer sites defined by corresponding codes from the International Classification of Diseases, version 10. *The group of cancer survivors aged 60–79 years had incidence similar to that of the group aged ≥80 years, resulting in a seemingly absent blue line in the graph.