Frailty status, aging, and mortality risk in heart failure

Abstract Background In heart failure (HF), the terms "aging" and "frailty" are often used interchangeably, despite representing different concepts. Aging is a natural chronological process, whereas frailty reflects a biological vulnerability to adverse outcomes and varies among patients within the same disease population. Understanding how frailty and aging differentially impact clinical outcomes in patients with HF is important for optimising patient management and guiding effective treatment strategies. Purpose This study aimed to assess how frailty modifies the relationship between age and two-year mortality risk in HF patients. Additionally, we evaluated the association between frailty and evidence-based HF treatment initiation. Methods Using nationwide Danish registries, we included all patients aged =18 years diagnosed with new-onset heart failure from March 1st 2013 to March 1st 2022. Patients were stratified into two frailty risk groups (low vs. intermediate/high) based on the Hospital Frailty Risk Score. Two-year all-cause mortality was assessed via logistic and multivariable Cox regressions. We also investigated how frailty was associated with evidence-based treatment (beta-blockers, ACE-inhibitors, mineralocorticoid receptor antagonists and sodium-glucose cotransporter 2 inhibitors) three months after diagnosis. Results We included 70,587 patients, of whom 42,561 (60%) were in the low frailty group and 28,026 (40%) were in the intermediate/high frailty group. Patients in the intermediate/high frailty group were older (mean age 76.6 SD 12.2) than those in the low frailty group (mean age 70.1 SD 13.5) and more often women (44% vs. 35%). Moreover, intermediate/high frailty status was associated with lower educational and income levels. Intermediate/high frailty status was associated with higher mortality risk across the age spectrum, though the strength of this association declined with age (age 65 HR 2.5 95% CI, 2.01-2.52; age 65-79 HR 1.8 95% CI, 1.71-1.92; age =80 HR 1.5 95% CI, 1.45-1.56). Notably, a 60-year-old patient with HF and intermediate/high frailty demonstrated a similar two-year absolute mortality risk as an 80-year-old patient with low frailty. Similar trends were seen in both men and women. Regardless of age, intermediate/high frailty was associated with lower treatment rates than low frailty. Conclusion Frailty is a strong predictor of mortality in HF patients, independent of age. However, its relative impact diminishes in the oldest patients. Frailty is also linked to a lower likelihood of receiving evidence-based HF treatment for all age groups. These findings highlight the importance of considering both age and frailty when managing patients with HF.