Cancer Incidence and Mortality According to Pre-Existing Heart Failure in a Community-Based Cohort

Abstract

Background: Studies assessing whether heart failure (HF) is associated with cancer and cancer-related mortality have yielded conflicting results.

Objectives: This study assessed cancer incidence and mortality according to pre-existing HF in a community-based cohort.

Methods: Among individuals ≥50 years of age from the Puglia region in Italy with administrative health data from 2002 to 2018, no cancer within 3 years before the baseline evaluation, and ≥5-year follow-up, the study matched 104,020 subjects with HF at baseline with 104,020 control subjects according to age, sex, drug-derived complexity index, Charlson comorbidity index, and follow-up duration. Cancer incidence and mortality were defined based on International Classification of Diseases-Ninth Revision codes in hospitalization records or death certificates.

Results: The incidence rate of cancer in HF patients and control subjects was 21.36 (95% CI: 20.98-21.74) and 12.42 (95% CI: 12.14-12.72) per 1000 person-years, respectively, with the HR being 1.76 (95% CI: 1.71-1.81). Cancer mortality was also higher in HF patients than control subjects (HR: 4.11; 95% CI: 3.86-4.38), especially in those <70 years of age (HR: 7.54; 95% CI: 6.33-8.98 vs HR: 3.80; 95% CI: 3.44-4.19 for 70-79 years of age; and HR: 3.10; 95% CI: 2.81-3.43 for ≥80 years of age). The association between HF and cancer mortality was confirmed in a competing risk analysis (subdistribution HR: 3.48; 95% CI: 3.27-3.72). The HF-related excess risk applied to the majority of cancer types. Among HF patients, prescription of high-dose loop diuretic was associated with higher cancer incidence (HR: 1.11; 95% CI: 1.03-1.21) and mortality (HR: 1.35; 95% CI: 1.19-1.53).

Conclusions: HF is associated with an increased risk of cancer and cancer-related mortality, which may be heightened in decompensated states.

Keywords: ATC, Anatomical Therapeutic Chemical; CCI, Charlson comorbidity index; DDCI, drug-derived complexity index; DP, drug prescription; HDR, hospital discharge record; HF, heart failure; HFW, health care cost-related fee waiver; ICD-9-CM, International Classification of Diseases-Ninth Revision-Clinical Modification; IR, incidence rate; SHR, subdistribution HR; cancer; cardio-oncology; comorbidity; heart failure; mortality.

Graphical abstract

Figure 1

Study Design (A) Cancer incidence and mortality were evaluated among individuals who were ≥50 years of age at the index date, did not have a history of cancer in the 3 years before inclusion, and had a follow-up of ≥5 years unless they were diagnosed with cancer, died, or moved to another region. (B) Selection of heart failure (HF) cases and control subjects for the assessment of the study outcomes. HDR = hospital discharge record; HFW = health care cost-related fee waiver.

Figure 2

Mortality in HF Patients vs Control Subjects Cumulative incidence and overall survival curves showing mortality for (A) cancer, (B) heart failure (HF), and (C) any cause, as assessed by International Classification of Diseases-9th Revision-Clinical Modification codes, in inhabitants of the Puglia region in Italy, without a history of cancer in the 3 years before the index date and with (red line) or without (black line) HF at baseline. CIF = cumulative incidence function.

Figure 3

Cancer Death in Heart Failure Patients According to Age and Sex Cause-specific HRs (point) and 95% CIs (bars) for cancer mortality in subjects with heart failure vs control subjects in the whole study population and across age and sex groups.

Central Illustration

Cancer Incidence and Mortality Are Increased in HF Patients This community-based study included individuals ≥50 years of age from the Puglia region in Italy, without cancer within 3 years before the baseline evaluation, and ≥5-year follow-up. After matching for age, sex, drug-derived complexity index, health care district, Charlson comorbidity index, and follow-up duration, subjects with heart failure (HF) had a higher risk of cancer incidence and mortality compared with subjects without HF. CIF = cumulative incidence function; HDR = hospital discharge record; HFW = health care cost-related fee waiver.