Association of Cardiovascular-Kidney-Metabolic Overlap with Physical Function and Prognosis in Older Patients with Heart Failure: A Post-hoc Analysis of the FRAGILE-HF and SONIC-HF.

Aims: The prevalence and impact of cardiovascular, kidney, and metabolic (CKM) overlap on physical function and prognosis in older patients with heart failure (HF) remain unclear. This study aimed to assess the impact of overlapping CKM conditions on physical function and prognosis in older patients with HF.

Methods: This post-hoc analysis of the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort), both prospective multicentre studies, included patients aged ≥65 years who were hospitalised for HF. CKM overlap was defined as the presence of one or more of the following comorbidities: atherosclerotic cardiovascular disease, chronic kidney disease, or type 2 diabetes mellitus. The primary outcome was a composite of all-cause death and HF readmission within 2 years. Physical function was assessed using gait speed, five-time chair stand test (5CST), short physical performance battery (SPPB), and 6-min walk test (6MWT). To validate the prognostic association of CKM overlap, we conducted an external validation using the SONIC-HF cohort, an independent prospective study with identical inclusion criteria.

Results: Of 1,113 patients (mean age: 80±8 years, 58.1% male), 193 (17.3%) had no CKM conditions, 370 (33.2%) had one, and 550 (49.5%) had two or three. A multivariable logistic regression model, adjusted for age, sex, comorbidities, and New York Heart Association functional class, showed that two or three CKM conditions were independently associated with lower physical function (5CST: odds ratio [OR]=1.91, P<0.001; SPPB: OR=1.87, P=0.001; 6MWT: OR=1.84, P=0.003). Kaplan-Meier analysis demonstrated a significant stepwise association between CKM overlap and the primary outcome in both the FRAGILE-HF and SONIC-HF cohorts (Log-rank: P < 0.001). Adjusted Cox analysis demonstrated that the overlapping CKM conditions were associated with the primary outcome, with two or more CKM conditions showing a statistically significant association in the FRAGILE-HF cohort (HR = 1.64, P = 0.003). Similarly, although statistical significance was not reached in the SONIC-HF cohort, a stepwise increase in HR was observed (2-3 CKM conditions: HR = 1.90, 95% CI: 0.97-3.73, P = 0.063).

Conclusion: Older patients with HF who have greater CKM overlap exhibited significantly poorer physical function and prognosis.