Interaction Between Frailty and Renal Function in Patients with Heart Failure

Background. Frailty is highly prevalent among patients with heart failure (HF) and is associated with adverse clinical outcomes. Chronic kidney disease (CKD) frequently coexists with HF and may further increase risk. However, the clinical profile linking frailty and CKD remains insufficiently characterized. This study aimed to determine the prevalence and clinical correlates of frailty in outpatients with HF and to assess whether its prognostic significance varies across CKD severity. Methods. A prospective, observational cohort of HF outpatients was enrolled. Frailty was defined according to Fried's phenotype (≥3 criteria). Factors associated with frailty were identified using logistic regression. The primary endpoint was a composite of all-cause mortality or HF hospitalization over one year. Cox proportional hazards models were used to evaluate associations between frailty and outcomes and to test its interaction with CKD. Results. A total of 459 HF outpatients (median age 75 [IQR 68-82] years; 72% men) were included. Frailty was present in 39.9% of patients and increased progressively with worsening renal function-from 14% in those with eGFR >60 to 38% in eGFR 30-60 and 48% in eGFR <30 mL/min/1.73 m² (p < 0.001). In multivariate analysis, older age, prior stroke, higher CA125 levels, and lower eGFR were independently associated with frailty. Frail patients had a higher risk of all-cause death or HF hospitalization (adjusted HR 2.09; 95% CI 1.22-3.58; p = 0.007), with an amplified effect among those with advanced CKD (HR 5.02; 95% CI 2.46-10.22; p < 0.001). Conclusions. In HF outpatients, frailty is common and closely linked to renal dysfunction. Its coexistence with advanced CKD identifies a subgroup at the highest risk of adverse outcomes. Combined assessment of frailty and renal function may enhance prognostic precision and guide more individualized therapeutic strategies.