Cancer diagnosis, cancer treatment, and association with cardiovascular disease in older adults: Results from ASPREE.
Authors: Muhandiramge Jaidyn , Zalcberg John Raymond , Haydon Andrew Mark , Warner Erica T. , Gibbs Peter , Polekhina Galina , Van Londen G J. , Orchard Suzanne G ,   ASPREE Investigator Group
Published: June 2022

12086

Background: New treatments and early detection measures have led to declines in cancer mortality rates and a growing population of cancer survivors at risk of short- and long-term effects of cancer and cancer treatment (C&CT), including cardiovascular disease (CVD). Although shared risk factors may contribute, several C&CT-related mechanisms including inflammation, treatment-related cardiotoxicity, and coagulation disorders may play a role. There are several studies exploring the link between C&CT and CVD; however, many do not examine risk stratified by cancer type or disease extent, nor investigate the impact of different treatment modalities. Methods: This analysis utilized data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, an international, multi-center, double-blinded randomized controlled trial that investigated the benefits and risks of aspirin in healthy older people. Multivariate time-dependent Cox regression models (adjusted for clinically significant factors including age, gender, smoking, and metabolic disease) were used to investigate the impact of C&CT on myocardial infarction, stroke, hospitalization for heart failure, and a composite endpoint combining these. Crude incidence rates were estimated using a competing risks regression model. Subgroup analysis was performed by metastatic status, cancer type, and treatment modality. Results: Of the 19,114 ASPREE participants (56% female; median age 75.1 years; median follow up 4.7 years), 1,933 received a post-randomisation cancer diagnosis. Participants with cancer had a greater rate and risk of CVD than those without cancer (15.3 per 1000 person-years (/1000pyrs] vs 10.5/1000pyrs, respectively; Hazard Ratio [HR] = 1.70, 95% Confidence Interval [CI] 1.32-2.10). The greatest increase in risk was seen for hospitalization for heart failure (HR 2.00, 1.18-3.38, 95% CI 1.18-3.38), although increases in risk were also seen for myocardial infarction, all-stroke, and ischaemic stroke. In subgroup analysis by cancer type, blood cancer (HR 2.33, 95% CI 1.25-4.36), lung cancer (HR 2.76, 95% CI 1.23-6.19), and melanoma (HR 1.97, 95% CI 1.02-3.82) were associated with an increased risk of composite CVD. ‘Any cancer treatment’ conferred increased risk of hospitalisation for heart failure (HR 1.78, 95% CI 1.15-2.75), although individual treatment modalities, including cytotoxic chemotherapy, targeted therapy, and radiotherapy conferred increased risks of various cardiovascular outcomes. Conclusions: Our findings indicate that both cancer and anti-cancer treatment confer risk for CVD in the elderly, the magnitude of which varied depending on cancer type and treatment modality. Given the implications of cardiovascular events for quality of life and mortality, these results support the integration of CVD screening and management into routine care for cancer survivors.