Understanding cardiovascular disease death risk in older cancer survivors

Cancer and cardiovascular disease are prevalent in older people and share many of the same risk factors. Older patients with cancer are more likely to die from causes other than their primary neoplasms, with cardiovascular disease being the predominant cause. Public health strategies need to consider how to reduce the impact of cardiovascular disease in older people with cancer. The number of older adults with cancer is increasing worldwide [1, 2] and management of their needs is complex [3]. Although age-related disparities in cancer survival still exist for most cancer types even after considering differences in background mortality [4], the number of cancer survivors aged over 65 is also expected to increase. In the United States, two out of three cancer survivors (i.e. any person who has been diagnosed with cancer) were aged over 65 in 2022 [5]. A key area of focus is to identify the primary causes of death in this demographic group to target interventions and treatments. Health promotion, disease prevention and management of chronic medical conditions are important yet under-researched areas in older people with cancer [6]. Both cancers and cardiovascular diseases (CVD) are prevalent in older adults and share many risk factors. In addition, the direct effect of some cancer biology, and certain cancer treatments themselves, increases the risk of CVD [7]. Cancer can also lead to systemic inflammation that triggers vascular damage, and its prothrombotic effects make a further contribution. These factors result in significant complexity when addressing how to manage CVD risk in older people with cancer, especially given the competing risk of polypharmacy and adverse drug events. The field of cardio-oncology has recently emerged to study this area and help guide oncologists and geriatricians working with older patients with cancer [8]. The goal is to optimally manage cancer whilst also reducing cardiovascular risk, and this also involves avoiding unnecessary overtreatment where the likelihood of death from cancer outweighs the long-term risk of cardiovascular death. Unfortunately, older patients with comorbidities tend to be excluded from cancer trials, which limits evidence-based practice. In the absence of high-quality interventional trials, the work by Guan et al. [9] urges a renewed focus on understanding and managing the risk of CVD death in this population. The study employed a retrospective, observational approach using data from the publicly available Surveillance, Epidemiology and End Results (SEER) programme. The authors focused on individuals aged 65 and older diagnosed with 16 specific cancers from 1975 to 2018, considering variables including age at diagnosis, sex, race, SEER stage, grade, year of diagnosis, length of follow-up and surgery. The objectives were: (i) identify and characterise the older patients with cancer subgroups with a higher CVD death; (ii) quantify the risk of CVD death in older patients with cancer compared to the general older population and (iii) compare the risk of CVD death amongst the 16 cancers. The authors identified 1,141,675 older patients with cancer; 55.1% were aged between 65 and 74 years, 35.1% were 75–84 years old, and 9.8% were 85 years and older. The largest proportion was diagnosed during 2004–2018 (39.6%). When analysing the causes of death, the authors found that older patients with cancer were more likely to die from causes other than their primary neoplasms, with CVD being the predominant cause. The proportion of deaths caused by CVD increased with survival time, whereas the proportion of deaths due to primary neoplasms decreased. This is consistent with findings from a previous study that showed the risk of dying from cancer is higher in the first year of diagnosis, mainly explained by the severity of the disease and the consequences of treatment [4]. Heart disease was found to be the leading cause of CVD-related deaths (75.5%), followed by cerebrovascular disease (17.8%). The trend of CVD-related deaths surpassing primary neoplasm-related deaths over survival time was consistent across demographic and tumour factors and was mainly explained by the cancer prognosis. The CVD-related death risk was higher for patients with good prognosis cancer types, i.e. prostate, breast cancers and melanomas, and lower for those with poor prognostic cancers such as pancreatic, gastric or lung cancers. The cumulative mortality from CVD exceeded that from the primary neoplasm over the survival time in the localised stage low-grade tumours, which are associated with better survival. When comparing the risk of CVD death in older patients with cancer to the general older population, the authors found that older patients with cancer had significantly increased standardised mortality ratios and absolute excess risks of CVD-related death. From an epidemiological perspective, this study offers a first description of the CVD risk in older adults with cancer. However, it is unfortunate that the authors were not able to distinguish patients with CVD at cancer diagnosis from those who develop CVD due to the treatment and some poor methodological decisions may have introduced biases (i.e. exclusion of patients dying within 2 months of diagnosis and including surgery that occurs after the start of follow-up of patients). Further studies are warranted to paint a full picture of the CVD burden in older cancer survivors. Firstly, it would be interesting to investigate how the risk of CVD in older patients with cancer evolves over time. The study by Guan et al covers 40 years during which cancer and CVD risk factor profile and management evolved considerably. Also, estimating the risk of CVD in patients both free of and with CVD at cancer diagnosis, separately and studying the impact of anti-cancer treatment on this risk in each group would help clinicians manage the risk and personalise cancer and CVD management. Well-designed observational studies using robust causal inference methods and well-defined estimands would be useful to estimate the effect of anti-cancer treatment on CVD risk in older adults with cancer considering lifestyle-related risk factors. Additionally, quantifying age-related differences in CVD risk amongst cancer survivors will complement our understanding of CVD risk. Perhaps most importantly, the effect of CVD on the quality of life and quality of death of older people with cancer merits an in-depth examination. This is an area that has been poorly addressed in cancer studies to date. From a clinical perspective, screening for cardiovascular risk before, during and after cancer treatment could play an important role in care for older patients with cancer [10]. Public health strategies need to consider how this group can be supported, and we need to broaden our understanding of how to provide optimal holistic management of both oncological and cardiovascular aspects. This would contribute to improving the health outcomes and quality of life of these patients. None. No new data were created or analysed in this study. Data sharing is not applicable to this article. SP is supported by the Luxembourg National Research Fund (FNR), Project n°16731054. The funders play no role in the study.