Is it time to include cancer in cardiovascular risk prediction tools?
Authors: Anne H Blaes, Chetan Shenoy
Journal: The Lancet (2019)

The number of cancer survivors worldwide has grown substantially to more than 16 million individuals in the USA. More than 65% of adults diagnosed with cancer live for at least 5 years after diagnosis, and a growing number of individuals live longer than that.1Miller KD Nogueira L Mariotto AB et al.Cancer treatment and survivorship statistics, 2019.CA Cancer J Clin. 2019; (published online June 11.)DOI:10.3322/caac.21565Crossref Scopus (2466) Google Scholar Although more individuals are cured from cancer or are living longer with cancer, evidence has been emerging that cancer survivors are at an increased risk of and death from cardiovascular disease.2Armenian SH Xu L Ky B et al.Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study.J Clin Oncol. 2016; 34: 1122-1130Crossref PubMed Scopus (256) Google Scholar Some anticancer therapies, such as anthracyclines, trastuzumab, and chest radiation, have been known for decades to increase cardiovascular risk. Several new treatments, such as immunotherapy, tyrosine kinase inhibitors, proteasome inhibitors, and anti-oestrogen therapies, are known to cause endothelial dysfunction and result in hypertension and an increase in cardiovascular events.3Blaes AH Thavendiranathan P Moslehi J Cardiac toxicities in the era of precision medicine: underlying risk factors, targeted therapies, and cardiac biomarkers.Am Soc Clin Oncol Educ Book. 2018; 38: 764-774Crossref PubMed Scopus (14) Google Scholar Additionally, increasing evidence exists of an overlap in the risk factors between the development of cardiovascular disease and cancer, and many individuals diagnosed with cancer have underlying cardiovascular risk factors, such as hypertension, advancing age, tobacco use, and diabetes, before ever starting anticancer therapies.4Koene RJ Prizment AE Blaes A Konety SH Shared risk factors in cardiovascular disease and cancer.Circulation. 2016; 133: 1104-1114Crossref PubMed Scopus (634) Google Scholar In The Lancet, Helen Strongman and colleagues5Strongman 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. 2019; (published online Aug 20.)http://dx.doi.org/10.1016/S0140-6736(19)31674-5Summary Full Text Full Text PDF PubMed Scopus (175) Google Scholar aimed to identify the long-term risk of cardiovascular disease in cancer survivors by use of primary care, hospital, and cancer registry data within the UK Clinical Practice Research Datalink. With these linked data, the authors were able to identify 108 215 cancer survivors and 523 541 controls for their main analyses. Of the cancer survivors, 51 541 (47·6%) were men and 56 674 (52·4%) were women; of the controls, 245 760 (46·9%) were men and 277 781 (53·1%) were women; and both survivors and controls had a median age of 67 years (IQR 58–76). Strongman and colleagues observed an increased risk of heart failure or cardiomyopathy in survivors of ten of 20 site-specific cancers compared with that of controls, including haematological (adjusted hazard ratio [HR] 1·94, 95% CI 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). The authors also found an increased risk of thromboembolism in 18 of 20 of site-specific cancers, with adjusted HRs ranging from 1·72 (1·57–1·89) in patients after prostrate cancer to 9·72 (5·50–17·18) after pancreatic cancer, as well as increases in the risk of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease for multiple other cancers. Although these risks were seen primarily in patients who received chemotherapy, these data are consistent with previous data reported by Armenian and colleagues,2Armenian SH Xu L Ky B et al.Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study.J Clin Oncol. 2016; 34: 1122-1130Crossref PubMed Scopus (256) Google Scholar who looked at the risk of cardiovascular disease in a cohort of 36 232 cancer survivors in the Kaiser Permanente Southern California registry. Within Armenian and colleagues's study, as well as in the Long Island Breast Cancer cohort,6Bradshaw PT Stevens J Khankari N Teitelbaum SL Neugut AI Gammon MD Cardiovascular disease mortality among breast cancer survivors.Epidemiology. 2016; 27: 6-13Crossref PubMed Scopus (231) Google Scholar the risk of cardiovascular events in breast cancer survivors increased and surpassed that of age-matched controls. Armenian and colleagues2Armenian SH Xu L Ky B et al.Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study.J Clin Oncol. 2016; 34: 1122-1130Crossref PubMed Scopus (256) Google Scholar also found an increase in cardiovascular events in survivors of Hodgkin lymphoma, lung cancer, and multiple myeloma compared with that of controls. The analysis by Strongman and colleagues is limited by the fact that they use registry data that do not provide details of cancer treatments, including specific chemotherapies, chemotherapy doses, and radiation doses and fields. Additionally, the dataset does not have granular details on other cardiovascular risk factors including hyperlipidaemia, diet, alcohol intake, exercise, age of menopause, and family history of cardiovascular disease, which are all well known risk factors for cardiovascular disease. Despite these limitations, the size and breadth of the linked data source allowed for enough data and statistical power to do a comprehensive analysis of long-term cardiovascular risk in survivors of 20 site-specific cancers. The study by Strongman and colleagues again shows that cancer therapies, particularly chemotherapy, play a prominent role in cardiovascular risk, a risk that might be similar to that of tobacco use and increased body-mass index. In clinical practice, the risk of cardiovascular events has been estimated with risk prediction tools such as the Framingham risk prediction score7Wilson PW D'Agostino RB Levy D Belanger AM Silbershatz H Kannel WB Prediction of coronary heart disease using risk factor categories.Circulation. 1998; 97: 1837-1847Crossref PubMed Scopus (7406) Google Scholar and the Pooled Cohort Equations.8Goff Jr, DC Lloyd-Jones DM Bennett G et al.2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation. 2014; 129: S49-S73Crossref PubMed Scopus (2335) Google Scholar These tools, used to identify individuals at high risk of developing cardiovascular disease in the short-to-medium term, do not include cancer as one of the risk factors. In survivors of childhood cancer, Chow and colleagues9Chow EJ Chen Y Hudson MM et al.Prediction of ischemic heart disease and stroke in survivors of childhood cancer.J Clin Oncol. 2018; 36: 44-52Crossref PubMed Scopus (68) Google Scholar, 10Chow EJ Chen Y Kremer LC et al.Individual prediction of heart failure among childhood cancer survivors.J Clin Oncol. 2015; 33: 394-402Crossref PubMed Scopus (148) Google Scholar showed an increased risk of cardiovascular events compared with that of controls who had not been diagnosed with cancer, with a clear demonstration that the Framingham risk score was not adequate in predicting risk of future cardiovascular events, such as heart failure and myocardial infarction, for these patients. Similar findings have been shown in small studies of breast cancer11Law W Johnson C Rushton M Dent S The Framingham risk score underestimates the risk of cardiovascular events in the HER2-positive breast cancer population.Curr Oncol. 2017; 24: e348-e353Crossref PubMed Scopus (19) Google Scholar and testicular cancer12Feldman DR Ardeshir-Rouhani-Fard S Monahan P et al.Predicting cardiovascular disease among testicular cancer survivors after modern cisplatin-based chemotherapy: application of the Framingham Risk Score.Clin Genitourin Cancer. 2018; 16: e761-e769Summary Full Text Full Text PDF PubMed Scopus (17) Google Scholar survivors. These studies and the work of Strongman and colleagues make a strong case for research into whether the inclusion of cancer in these risk prediction tools, beyond the traditional risk factors for the prediction of cardiovascular disease risk, would add incremental value in the general population. In the meantime, clinicians should account for cancer, and especially chemotherapy, as a risk factor for cardiovascular disease when discerning individual patient risks to guide preventive interventions. We declare no competing interests. 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 databasesSurvivors 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. Full-Text PDF Open Access