In a population-based cohort study, published on 20 August 2019 in The Lancet, the researchers 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 in adults who were alive 12 months after diagnosis and controls without history of cancer. The study team found that survivors of most site-specific cancers had increased medium- to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between tumour types.
Improvements in cancer survival in the past years have resulted in a large and growing population of long-term cancer survivors. In particular, in high-income settings about half of patients diagnosed with cancer are now expected to survive for 10 years or longer. However, significant concerns exist that there might be increased risk of cardiovascular diseases after diagnosis of cancer, driven by cardiotoxic treatment effects, mechanisms directly related to cancer biology, and shared risk factors, such as smoking and increased body-mass index.
The authors wrote in the study background that although randomised trials have shown short- 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. Several observational studies comparing survivors of adolescent-onset 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 cardiovascular disease. However, results varied by age, suggesting that estimates from these studies might not generalise to adult-onset cancer survivors.
The study team searched PubMed and OVID MEDLINE for epidemiological studies, reviews, and guidelines published in English from 1 January 2008 to 31 December 2018, using search terms for cardiovascular outcomes and cancer. In total, 21 studies were included in the analysis; eight focused on cardiovascular risks in patients after breast cancer and seven included multiple cancer sites, but six of these were restricted to adolescent-onset and young adult-onset cancers. The most commonly studied outcomes were coronary artery disease and stroke. 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 malignancy. Increased risks of heart failure or cardiomyopathy were observed in patients after several types of cancers, notably haematological malignancies. Elevated risks of venous thromboembolism were seen in most studies of this outcome, though few estimates were available per cancer site. Little previous evidence was available for other outcomes.
Long-term follow-up after cancer is increasingly available through linked electronic health record databases. In order to address the evidence gaps, the study investigators used large-scale electronic health records data from multiple linked UK databases to quantify the absolute and relative risks of a range of cardiovascular diseases in survivors of the 20 most common site-specific adult cancers, covering more than 90% of all cancer diagnoses, compared with healthy controls from the general population matched for age, sex, and general practice. They also investigated the extent to which relative risk differences are driven by shared risk factors, demographic characteristics, and use of chemotherapy and radiotherapy.
Between 1 January 1990 and 31 December 2015, 126120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630144 controls. After exclusions, 108215 cancer survivors and 523541 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 in patients after prostate cancer to 9.72 after pancreatic cancer. The HRs decreased over time, but remained elevated more than 5 years after diagnosis.
The study team observed increased risks of heart failure or cardiomyopathy in patients after 10 of 20 cancers, including haematological (adjusted HR 1.94 with non-Hodgkin lymphoma, 1.77 with leukaemia, and 3.29 with multiple myeloma), oesophageal (1.96), lung (1.82), kidney (1.73) and ovarian cancer (1.59).
Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies.
The 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.
This study is one of the largest to date to compare risks for a wide range of cardiovascular disease outcomes between adult survivors of multiple site-specific cancers and controls with no history of cancer, with a consistent methodological approach that allowed to reveal detailed patterns of risk.
The authors commented that one difficulty with managing post-cancer risk of cardiovascular disease has been that the long-term follow-up is typically done by cancer specialists, leading to insufficient focus on potential cardiovascular disease sequelae. Cardio-oncology clinics that bring together oncologists, cardiologists, and specialist nurses are starting to appear and will help to address this growing clinical problem.
Primary care physicians are also key for early prevention, and a pressing need exists to raise awareness among general practitioners of the increased cardiovascular disease risks in cancer survivors.
The study team has also showed recently that cancer survivors were no more likely to receive cardioprotective medications than controls without a history of cancer, with low uptake in both groups. More and better education and awareness is needed among general practitioners, other clinicians, and patients, so that preventive strategies can be considered and implemented, covering the extended time course during which cardiovascular disease risk might be elevated.
The authors commented that available information for clinicians is insufficient, and the development of comprehensive, evidence-based guidance on cardiovascular considerations in cancer survival care could be prioritised to help optimise the care of this patient group.
In conclusion, survivors of most site-specific cancers had increased medium- to long-term risk for one or more cardiovascular diseases compared with that for the general population, with patterns of risk varying by cancer site and by specific cardiovascular disease outcome. There was a substantially increased risk of venous thromboembolism for most cancers and increased risks of heart failure or cardiomyopathy in survivors of half of cancers investigated. Risks of other cardiovascular disease outcomes, including coronary artery disease and stroke, were elevated in survivors of several specific cancers, including haematological malignancies. Associations between cancer and cardiovascular risk did not appear to be explained by shared risk factors, but exploratory analyses highlighted chemotherapy as an important driver of risk. Strategies to minimise and manage cardiovascular risk are needed for the growing population of cancer survivors.
The study was funded byWellcome Trust and Royal Society.
Reference
Strongman H, Gadd S, Matthews A, et al. 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. Lancet; Published online 20 August 2019.DOI:https://doi.org/10.1016/S0140-6736(19)31674-5