Circulating Level of Growth‐Differentiation Factor 15 and Mortality of Patients With Acute Heart Failure: A Meta‐Analysis

BACKGROUND: Growth differentiation factor-15 (GDF-15) is a stress-responsive biomarker implicated in inflammation and myocardial injury. Its prognostic value for mortality risk in acute heart failure (AHF) remains uncertain. This meta-analysis evaluated the association between elevated admission circulating GDF-15 levels and subsequent mortality in patients hospitalized with AHF. METHODS: PubMed, Embase, and Web of Science were systematically searched for prospective or retrospective cohort studies and post-hoc trial analyses enrolling adult AHF patients with blood GDF-15 measured on admission. Risk ratios (RRs) for all-cause mortality comparing high versus low GDF-15 categories were pooled using random-effects models incorporating the influence of potential heterogeneity. RESULTS: Ten studies with 3724 patients with AHF were included. Overall, high admission GDF-15 levels were significantly associated with increased mortality risk during follow-up (RR = 2.82, 95% CI: 2.39-3.32; p < 0.001), with no evidence of between-study inconsistency (I² = 0%). Sensitivity analyses confirmed robustness (leave-one-out RR range: 2.73-3.00), and results remained consistent in high-quality studies (NOS ≥ 8; RR = 2.72, 95% CI: 2.26-3.27). Subgroup analyses demonstrated similar associations across Asian and Western cohorts, prospective and retrospective designs, different sampling times (at admission to within 48 h), assay methods (ELISA vs. ECLIA), cutoff definitions, follow-up duration, and adjustment for BNP/NT-proBNP (all p for subgroup differences >0.05). No significant publication bias was detected (Egger's p = 0.59). CONCLUSIONS: Elevated circulating GDF-15 levels at admission are strongly associated with increased mortality risk in patients with AHF, supporting its potential role in early risk stratification.