A population-based study of cardiovascular disease mortality risk in US cancer patients

Abstract

Aims: This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis.

Methods and results: The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973-2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at <35 years of age. Further, CVD mortality risk is highest (SMR 3.93, 95% confidence interval 3.89-3.97) within the first year after cancer diagnosis, and CVD mortality risk remains elevated throughout follow-up compared to the general population.

Conclusion: The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.

Keywords: Cardio-oncology; Epidemiology; Heart disease; Neoplasm; SEER.

Figure 1

Yearly cardiovascular death in cancer patients by cancer site. All deaths from cardiovascular causes in cancer survivors between 1973 and 2012 are categorized by cancer site. Cancer site and its representative colour are listed to the right of the graph and in descending order of appearance on the graph.

Figure 2

Plots of patient death vs. attained calendar year (from 1973 to 2012), for cancer sites with <20% decline in death due to index-cancer. Death was characterized as due to ‘index-cancer’, (black lines; i.e. the cancer originally diagnosed in the patient) and ‘cardiovascular disease’ (red lines). Attained calendar year refers to the year in which the death occurred.

Figure 3

Plots of patient death vs. attained calendar year (from 1973 to 2012), for cancer sites with decreasing deaths due to index-cancer, yet, death from index-cancer still remains >10% higher than death from cardiovascular disease. Death was characterized as due to ‘index-cancer’, (black lines; i.e. the cancer originally diagnosed in the patient) and ‘cardiovascular disease’ (red lines). Attained calendar year refers to the year in which the death occurred.

Figure 4

Plots of patient death vs. attained calendar year (from 1973 to 2012), for cancer sites where death from index-cancer is either <10% higher than death from cardiovascular disease, or death from cardiovascular disease has surpassed death from index-cancer. Death was characterized as due to ‘index-cancer’, (black lines; i.e. the cancer originally diagnosed in the patient) and ‘cardiovascular disease’ (red lines). Attained calendar year refers to the year in which the death occurred.

Figure 5

Cardiovascular disease mortality ratio by age at diagnosis and follow-up time in cancer patients. Standardized mortality ratios for the six types of cardiovascular diseases were characterized after diagnosis (all cancer sites), binned by patient age at diagnosis (A and B) and binned by period of follow-up time (C and D). Risk for cardiovascular disease mortality was assessed both historically (A and C) and specifically restricted to the modern treatment era (B and D). A standardized mortality ratio above 1 represents a higher relative risk of death for a type of cardiovascular cause, when compared to the general population (>1000 person years of risk for graphical inclusion).

Take home figure

Standardized morality ratios for cancer sites with both ≤30% risk of death from the index-cancer and ≥20% risk of mortality from heart disease were calculated and binned by follow-up time. Cancers sites with at least 1000 person years of risk for death from heart disease between 2000 and 2015 were displayed.