Higher risk of cardiovascular mortality than cancer mortality among long-term cancer survivors

Abstract

Background: Previous studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death.

Methods: Time trends in the proportions of CV death (P_CV), cancer death (P_CA), and other causes in deaths from all causes were used to show preliminary relationships among the three causes of death in 4,806,064 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER) program. Competing mortality risk curves were used to investigate when the cumulative CV mortality rate (CMR_CV) began to outweigh the cumulative cancer mortality rate (CMR_CA) for patients with cancer who survived for more than 10 years. Multivariable competing risk models were further used to investigate the potential factors associated with CV death.

Results: For patients with cancer at all sites, the P_CV increased from 22.8% in the 5th year after diagnosis to 31.0% in the 10th year and 35.7% in the 20th year, while the P_CA decreased from 57.7% in the 5th year after diagnosis to 41.2 and 29.9% in the 10th year and 20th year, respectively. The P_CV outweighed the P_CA (34.6% vs. 34.1%) since the 15th year for patients with cancer at all sites, as early as the 9th year for patients with colorectal cancer (37.5% vs. 33.2%) and as late as the 22nd year for patients with breast cancer (33.5% vs. 30.6%). The CMR_CV outweighed the CMR_CA since the 25th year from diagnosis. Multivariate competing risk models showed that an increased risk of CV death was independently associated with older age at diagnosis [hazard ratio and 95% confidence intervals [HR (95%CI)] of 43.39 (21.33, 88.28) for ≥ 80 vs. ≤ 30 years] and local metastasis [1.07 (1.04, 1.10)] and a decreased risk among women [0.82 (0.76, 0.88)], surgery [0.90 (0.87, 0.94)], and chemotherapy [0.85 (0.81, 0.90)] among patients with cancer who survived for more than 10 years. Further analyses of patients with cancer who survived for more than 20 years and sensitivity analyses by cancer at all sites showed similar results.

Conclusion: CV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors.

Keywords: anticancer treatment; cancer; cardio-oncology; cardiovascular deaths and mortality; long-term cancer survivors.

FIGURE 1

Temporal trends in the proportions of cardiovascular (CV) death (P_CV), cancer death (P_CA), and other causes in all-cause deaths in patients with cancer. CVD, cardiovascular disease; RESPIR, respiratory; BREAST, breast; COLRECT, colon and rectum; URINARY, urinary; LYMYLEUK, lymphoma of all sites and leukemia; FEMGEN, female genital; MALEGEN, male genital; DIGOTHR, other digestive; OTHER, all other sites.

FIGURE 2

Competing mortality risk curves for patients with cancer who survived for more than 20 years by cancer sites. CVD, cardiovascular disease; RESPIR, respiratory; BREAST, breast; COLRECT, colon and rectum; URINARY, urinary; LYMYLEUK, lymphoma of all sites and leukemia; FEMGEN, female genital; MALEGEN, male genital; DIGOTHR, other digestive; OTHER, all other sites.

FIGURE 3

Cardiovascular mortality risk and anticancer treatments for patients with cancer who survived for more than 20 years by cancer sites. *A p-value of < 0.05. Marital status at diagnosis, race, calendar years at diagnosis according to 1970s, 1980s, 1990s, 2000s, 2010s, nine original registries, sex, SEER historic stage, surgery, radiotherapy and chemotherapy were adjusted in the multivariate competing risk regression models. HR (95%CI), Hazard ratio (95% confidence intervals); RESPIR, respiratory; BREAST, breast; COLRECT, colon and rectum; URINARY, urinary; LYMYLEUK, lymphoma of all sites and leukemia; FEMGEN, female genital; MALEGEN, male genital; DIGOTHR, other digestive; OTHER, all other sites.