Adipokine Profile in Acute Heart Failure: Associations with Natriuretic Response and Prognosis

BACKGROUND: Adipose tissue signaling is linked to heart failure (HF), but its role in acute HF (AHF), especially concerning early diuretic response, is unclear. Early natriuretic response to loop diuretics is vital for effective decongestion. OBJECTIVES: To characterize and evaluate the associations between circulating adipokine profiles, early natriuretic response, and clinical outcomes in AHF. METHODS: We conducted a prospective observational study including 262 consecutive AHF patients. Early diuretic response was assessed by measuring post-diuretic spot urine sodium (uNa+) 2 hours after intravenous loop diuretic administration. Associations between adipokines and uNa+ were assessed, and an adipokine score was constructed based on markers associated with uNa+. Clinical outcomes (all-cause mortality and a composite of death or HF hospitalization) were evaluated over 1-year using Cox regression models. RESULTS: Patients with impaired natriuretic response (uNa+ <90 mmol/L) exhibited higher levels of selected Domain-3 adipokines, including chemerin and FABP4. Individual adipokines showed modest associations with early natriuretic response. Visfatin was significantly associated with lower post-diuretic uNa+, while IL-6, FABP4, and Adipsin demonstrated directional but non-significant trends. An adipokine score integrating these selected adipokines was independently associated with uNa+ after multivariable adjustment (β 3.37, 95% CI 1.51-5.23; p<0.001). During a 1-year follow-up, several adipokines: IL-6, resistin, and FABP4, were independently associated with mortality, while FABP4 consistently demonstrated associations with both impaired natriuresis and adverse outcomes. CONCLUSIONS: In AHF, individual adipokines are modestly associated with the early natriuretic response, whereas an integrated adipose-inflammatory profile shows a more consistent association with sodium excretion and adverse outcomes. These findings suggest that adipokine signaling may reflect biological pathways associated with diuretic response and prognosis, though the results should be considered hypothesis-generating.