Abstract
SummaryBackgroundThe 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.MethodsFor 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.FindingsBetween 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.InterpretationSurvivors 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.FundingWellcome Trust and Royal Society.
Highlights
Improvements in cancer survival in the past few decades have resulted in a large and growing population of longterm cancer survivors; about half of patients diagnosed with cancer in high-income settings are expected to survive for 10 years or longer.[1]
We identified articles that provided estimates comparing risks of any of the specific cardiovascular disease outcomes included in our study between adult survivors of one or more site-specific cancers and controls without a history of cancer. 21 studies were included; eight focused on cardiovascular risks in patients after breast cancer and seven included multiple cancer sites, but six of these were restricted to teenage-onset and young adult-onset cancers
Study design and participants In this population-based cohort study, we identified 20 matched cohorts to compare risks of cardiovascular disease outcomes in survivors of the 20 most common site-specific cancers[1] with those of cancer-free controls, using Clinical Practice Research Datalink primary care data (CPRD GOLD) linked to national data on hospital admissions from the Hospital Episode Statistics Admitted Patient Care (HES APC) database, cancer registrations from the National Cancer Registration and Analysis Service (NCRAS), death registrations—including cause of death information—from the Office of National Statistics mortality database, and postcode-based index of Multiple Deprivation data.[12,13]
Summary
Improvements in cancer survival in the past few decades have resulted in a large and growing population of longterm cancer survivors; about half of patients diagnosed with cancer in high-income settings are expected to survive for 10 years or longer.[1]. Randomised trials have shown short-term to medium-term adverse cardiovascular effects of some specific cancer treatments, such studies cannot quantify the broader differences in risk between cancer survivors and individuals with no history of cancer.[2] Several observational studies[9] comparing survivors of adolescent and young adult-onset cancer with age-matched controls with no history of cancer or controls from a general population found substantially increased risks of cardio vascular disease during the time after survival. We identified articles that provided estimates comparing risks of any of the specific cardiovascular disease outcomes included in our study between adult survivors of one or more site-specific cancers and controls without a history of cancer. Some evidence was found of increased risks of both outcomes in patients after non-Hodgkin lymphoma, whereas stroke risk was markedly elevated for survivors of CNS cancer in all three relevant studies.
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