Heart Failure History May Indicate Greater Risks of Cancer, Related Mortality

This study from Italy investigated potential associations between heart failure and comorbid cancer and whether the existence of heart failure predisposed individuals with both to a higher risk of death.

There are increased risks of cancer and of cancer-related mortality among individuals who have coexistent heart failure, reports a new study from Italy. In addition, both risks may be even greater in the presence of decompensated heart failure, which is the sudden onset of volume overload and requires immediate medical attention.

These findings were published recently in JACC: CardioOncology.

“The interconnection between cancer and heart failure is increasingly recognized, but it remains unclear whether heart failure is associated with an excess risk of cancer and cancer-related mortality,” the authors explained. “In this context, we assessed cancer incidence and mortality in a large cohort of heart failure patients compared with matched control subjects.”

Their study classified participants into 2 cohorts: heart failure at baseline (n = 104,020) and controls (n = 104,020) matched by age, sex, drug-derived complexity index, Charlson comorbidity index, and follow-up duration. International Classification of Diseases, Ninth Revision codes and death certificates defined cancer incidence and mortality, and health care cost-related fee waivers (HFWs) for heart failure in the previous year or a hospital discharge record (HDR) with a heart failure diagnosis.

For the years of this retrospective community-based study, cancer occurred 1.7 times faster in the heart failure cohort than the control cohort. There were 21.36 (95% CI, 20.98-21.74) cases compared with 12.42 (95% CI, 12.14-12.72) per 1000 person-years, with an overall 76% greater risk (HR, 1.76; 95% CI, 1.71-1.81). Risk of cancer-related death was also higher in the study group overall (HR, 4.11; 95% CI, 3.86-4.38).

Stratifying by age showed even higher risks of cancer-related mortality; in particular that the youngest patients with heart failure—evaluated ages were younger than 70 years (n = 57,328), 70 to 79 years (n = 70,156), and 80 years and older (n = 80,556)—had a mortality risk that was more than twice as high as the oldest patients:

  • Younger than 70 years: HR, 7.54 (95% CI, 6.33-8.98)
  • Aged 70 to 79 years: HR, 3.80 (95% CI, 3.44-4.19)
  • 80 years and older: HR, 3.10 (95% CI, 2.81-3.43)

A competing risk analysis for other causes of death also confirmed that presence of heart failure led to a greater risk of death from cancer (subdistribution HR [SHR], 3.48; 95% CI, 3.27-3.72) overall and across all age groups:

  • Younger than 70 years: SHR, 6.65 (95% CI, 5.60-7.94)
  • Aged 70 to 79 years: SHR, 3.14 (95% CI, 2.84-3.48)
  • 80 years and older: SHR, 2.81 (95% CI, 2.55-3.10)

Further, among patients with heart failure who were taking high-dose loop diuretics, there were elevated incidences of cancer (HR, 1.11; 95% CI, 1.03) and of death (HR, 1.35; 95% CI, 1.19-1.53), and women with heart failure at baseline had a higher risk of cancer mortality (HR, 4.86; 95% CI, 4.35-5.43) vs men (HR, 3.79; 95% CI, 3.51-4.10), although both risks were elevated.

All study participants were at least 50 (mean [SD], 76 [10]) years of age between January 1, 2005, and December 31, 2013; from the Puglia region of Italy; had administrative health data (drug prescriptions, outpatient visit reports, HDRs, HFWs, death certificates) from between 2002 and 2018; did not have cancer in the 3 years before the study’s baseline evaluation; and had at least 5 years of follow-up data on record.

The most common cardiovascular risk factor overall was hypertension, the most common prescribed cardiovascular drug class was diuretics, and the most common cardiovascular disease was stable coronary artery disease among study and control subject aged younger than 70 years through 79 years. Among participants 80 years and older, atrial fibrillation was most common among the heart failure group and stroke among the control group.

To minimize surveillance bias—patients with heart failure have more medical evaluations vs healthy subjects—the study investigators also stratified their cohorts by total hospital admissions, after which they assessed cancer incidence and mortality in all. Again, cancer incidence and mortality were higher among the persons with heart failure.

While their observational design may bias generalizability of these results, having a large study population, utilizing an unbiased selection process, including a long follow-up, and confirming heart failure diagnosis through health care records serve to strengthen their conclusion that individuals with heart failure are more likely to develop and die from cancer.


Bertero E, Robusto F, Rulli E, et al.Cancer incidence and mortality according to pre-existing heart failure in a community-based cohort. JACC CardioOncol.Published online January 18, 2022. doi:10.1016/j.jaccao.2021.11.007

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