Does Cardiovascular Mortality Overtake Cancer Mortality During Cancer Survivorship?

Background Cancer survivors have a higher risk for developing cardiovascular diseases than the general population. Objectives The aim of this study was to investigate whether cardiovascular mortality overtakes cancer-specific mortality during cancer survivorship and, if so, at what point cardiovascular disease becomes the dominant cause of death. Methods This cohort study used linked English electronic health records, including death registration data. The study population included 104,028 adults ≥40 years of age whose first cancer diagnosis was for 1 of 9 common cancers and who were alive and followed up at least 1 year after diagnosis. Age-stratified mortality rates were estimated from cardiovascular disease or cancer by predicting from Poisson models incorporating categorical age at diagnosis and time since diagnosis. Where cardiovascular disease mortality overtook cancer mortality, the crossover point was estimated using interpolation. Results Mortality from cardiovascular causes overtook mortality due to the primary cancer at 2 to 11 years after cancer diagnosis in survivors of all 9 cancer types ≥80 years of age at diagnosis and after 5 to 17 years in survivors of 7 cancer types 60 to 79 years of age at diagnosis. Cardiovascular mortality overtook all cancer mortality for 6 and 2 cancer sites in the ≥80-year and 60- to 79-year age groups, respectively, over a longer time period. Cardiovascular mortality did not overtake cancer mortality during the observation period in patients aged 40 to 59 years, except among survivors of uterine cancer. Conclusions In older survivors of 9 common cancers, cardiovascular mortality becomes dominant over mortality from the primary cancer, though not always over total cancer mortality, as time passes since cancer diagnosis.

C ancer and cardiovascular disease are competing causes of death in England; each accounted for approximately 30% of deaths in 2019, with cardiovascular disease causing more deaths in older age groups (>70 years for women, >80 years for men) and neoplasms being dominant in younger age groups. 1 With improvements in cancer detection and care, people are living longer after cancer. 2 Adult survivors of most cancer sites are at higher risk for cardiovascular disease compared with the general population, with variation in the size and duration of risk among cancer sites and age groups. 3 Compared with the general population, cardiovascular mortality has been shown to be elevated in survivors of cancer from several sites, [4][5][6][7] with most studies investigating breast cancer 8 or lymphoma. 9 To raise awareness of the risk for cardiovascular disease in cancer survivors and inform patient counseling and decisions about monitoring and priorities for disease prevention, it is important to establish how risk for death of cardiovascular disease competes with risk for death of cancer over time.
Studies from the United States have estimated that in people who survive breast and endometrial cancers, cardiovascular mortality exceeds mortality from the primary cancer after 10 to 15 and 5 years, respectively. [10][11][12][13] These analyses support long-term monitoring of cardiovascular risk in addition to cancer recurrence in breast and endometrial cancer survivors. It is not clear, however, how mortality risks from cancer and cardiovascular diseases compare over time following diagnosis of a wider range of cancers or how differences in these cause-specific mortality risks vary by age at cancer diagnosis.
We therefore aimed to identify whether, and at what time point, risk for cardiovascular mortality overtakes risk for mortality from the primary cancer and all cancers combined, by age, in survivors of the 9 most common cancers in England.

METHODS
For this retrospective cohort study, we identified cohorts of survivors of 9 different types of cancer using Clinical Practice Research Datalink primary care data in England (CPRD GOLD), 14 linked to national data 15

on hospital admissions from Hospital Episode
Statistics Admitted Patient Care, 16 cancer registrations from the National Cancer Registration and Analysis Service, 17

PARTICIPANTS, EXPOSURES AND OUTCOMES.
Cohort development has been described previously. 3 We included individuals with a first ever cancer record from 1 of the 9 most common cancer sites ( Figure 1) in Read-coded CPRD GOLD data or Inter-  19 We did not end follow-up when individuals left the primary care practice, as the outcome (cause-specific mortality) was measured in linked national death registration data. We described the number of individuals in the study population and for each age and cancer site grouping with the number and percentage who were female, median (IQR) follow-up from index, and the number of deaths due to cardiovascular disease, the primary malignancy, and all malignancies. We additionally described mean age at diagnosis for the full study population. Individual follow-up time was divided into groups of 1 to <2, 2 to <3, 3 to <4, 4 to <5, 5 to <10, 10 to <15, and 15 to 25 years since diagnosis.
We fit Poisson models for each cancer site and cause-specific mortality outcome, with age and time              low rates of excess cardiovascular deaths (3.6 per 10,000 patient-years). 20 Our findings in older age groups are also consistent with cardiovascular disease overtaking cancer as the leading cause of death in the general population in older age groups.
We also previously showed that patterns of car-