Age-related excess mortality in patients with heart failure with reduced ejection fraction compared with a matched general population cohort

Background Heart failure with reduced left ventricular ejection fraction ≤40% (HFrEF) affects individuals of all ages and is associated with increased mortality. However, the extent to which age at diagnosis contributes to excess mortality compared to the general population is largely unknown. Purpose This study assessed 5-year age-related mortality in patients with newly diagnosed HFrEF and examined excess mortality by comparing with a sex- and age-matched general population cohort. Methods We included patients with newly diagnosed HFrEF examined by first-time coronary angiography (CAG) between 2010 and 2021 in Western Denmark. Eligibility criteria were an ejection fraction between 10-40% and age 40 to 85 years at the time of the CAG. Patients with previous ischemic disease or an implantable cardioverter defibrillator were excluded. Patients were stratified into seven age groups and compared with a Danish sex- and age-matched general population cohort without known HFrEF or ischemic heart disease. The outcome was 5-year all-cause mortality. We calculated cumulative incidence proportions (CIP), risk differences (RD), and sex- and age-adjusted hazard ratios (aHR) using the matched general population cohort as a reference. Results A total of 5,425 patients aged 40 to 85 years with HFrEF were included and compared with 27,087 matched controls from the general population. Median age was 67 years (first quartile and third quartile (Q1-Q3): 59-74 years), 72% were male, and patients were examined with CAG a median of 33 days (Q1-Q3: 8-111 days) after their heart failure diagnosis. Patients with HFrEF had higher mortality across all age groups compared with matched controls (Figure). Notably, younger patients aged 50-54 had a similar 5-year risk as those aged 70-74 from the general population (approximately 12%; Figure). The 5-year risk increased from 8% in those aged 40-49 to 41% in those aged ≥75 in the HFrEF cohort, compared with an increase from 1% to 27% in the matched controls (Table). The greatest absolute RD (17%, 95% confidence intervals (CI): 14%-20%) was observed in those aged 65-69 years (aHR: 3.58, 95% CI: 2.98-4.32), while the greatest relative risk was in the youngest (aged 40-49 years) patients compared with their matched controls (aHR: 6.31, 95% CI: 3.72-11.05). Conclusion In this contemporary cohort of patients with newly diagnosed HFrEF, a 5-year mortality of >10% was reached approximately 20 years earlier than in the general population. The largest relative risk was observed in the youngest age group, while the largest absolute excess risk was found for HFrEF patients ≥65 years. These results show that age at HFrEF onset is critical for excess mortality.