One-year mortality risk after new onset comorbidity and worsening heart failure in patients with chronic heart failure
Authors: Madelaire C , Blanche P , Gustafsson F , Kober L , Torp-Pedersen C , Banke A , Kristensen S.L , Andersson C , Gislason G , Schou M 
Published: November 2020

Abstract

Background
Heart failure (HF) is a progressive disease characterized by risk of congestion and often accompanied by a significant burden of comorbidities. At the time of HF diagnosis, these are associated with a poor outcome, but it is relatively unknown whether hospitalization due to new-onset comorbidities carries the same subsequent mortality risk as hospitalization for worsening HF.

Purpose
To assess one-year mortality risk after hospitalization due to new-onset chronic comorbidity compared to a hospitalization with worsening HF in a nationwide cohort of patients with HF.

Methods
In Danish administrative registers, we identified all patients, aged 40–95 years with a first-time HF diagnosis from 2000 through 2016. Patients were included if they survived the initial 120 days and collected prescribed renin-angiotensin system inhibitor and beta-blocker. In analyses stratified on age and baseline burden of comorbidity (based on Charlson Comorbidity Index (CCI) excluding myocardial infarction and HF, we estimated absolute one-year mortality risk continuously during follow-up, using landmarking and flexible semi-parametric methods. If a patient had a comorbidity hospitalization equivalent to an increase in his/ her CCI or a HF hospitalization, one-year mortality risk was estimated immediately hereafter. In analyses assuming constant risks during follow-up, we calculated absolute risks and risk ratios for new comorbidity- or HF hospitalizations compared to patients without events.

Results
We included 81,788 patients, median age 72 (Q1-Q3:63–80), 36% women. At baseline, 57% had CCI=0, 22% CCI=1, 9% CCI=2 and 12% CCI≥3. High age and baseline CCI were associated with increased mortality risk throughout follow-up. Both new comorbidity- and HF hospitalizations at any time during follow-up were associated with increased mortality risk (p&lt;0.001) (Figure), and the risk was approximately constant over time. Among patients with baseline CCI=0, new-onset comorbidity (incident increase in CCI) was associated with a higher mortality risk than a HF hospitalization in all age groups, risk ratios with “no event” as reference: Age 40–64: 5.4 (95%-CI: 4.5–6.4) vs 2.5 (95%-CI: 2.1–2.9); age 65–74: 4.2 (95%-CI: 3.7–4.7) vs 2.2 (95%-CI: 1.9–2.5); age 75–84: 3.4 (95%-CI: 3.2–3.7) vs 2.3 (95%-CI: 2.1–2.5) and age 85–95: 2.6 (95%-CI: 2.4–2.8) vs 2.2 (95%-CI: 2.0–2.4) (figure). Across all strata, new-onset comorbidity was associated with at least similar risk as a HF hospitalization at any time during follow-up.

Conclusions
For patients with HF, hospitalization for new-onset chronic comorbidity was associated with at least the same mortality risk as worsening HF, independently of age. This finding highlights the prognostic impact of comorbidity for patients with HF and warrants further investigations in the mechanisms underlying the mortality.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Danish Heart Foundation