Three-Phase Serum Concentration Kinetics of FGF23 in a Clinical Model of Acute Myocardial Infarction

急性心肌梗死临床模型中FGF23血清浓度动力学的三相变化

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Abstract

BACKGROUND: Fibroblast growth factor-23 (FGF23) is a key regulator of phosphate homeostasis and an emerging biomarker in cardiovascular disease. Emerging data suggest that FGF23 may also contribute to the pathophysiology of myocardial infarction (MI), but existing studies have largely focused on non-acute stages. To address this gap, we investigated early FGF23 regulation by characterizing serum concentration kinetics over the first 24 h following MI, using both a clinical MI model (TASH) and a cohort of patients with ST-elevation myocardial infarction (STEMI). METHODS: Circulating FGF23 concentrations (cFGF23; RU/mL) were determined by C-terminal ELISA in patients with preserved renal function (eGFR > 30 mL/min/1.73 m(2)). TASH (transcoronary septal ablation) was carried out in patients with hypertrophic obstructive cardiomyopathy (n = 38). Venous serum samples were taken at baseline (pre-TASH) and at 30', 60', 2 h, 4 h and 24 h post-TASH. For the STEMI cohort (n = 18), serum was sampled immediately before and 3 h after coronary recanalization. All samples were processed using standardized procedures prior to analysis. Changes over time were assessed using the Friedman test with Bonferroni-corrected pairwise Wilcoxon comparisons. RESULTS: FGF23 concentrations changed significantly over time after TASH (Friedman test, p < 0.000001, Kendall's W = 0.518). Baseline FGF23 was 28.9 (19.4-71.0) RU/mL and increased significantly at 30' (68.2 (36.2-178.7) RU/mL, adjusted p < 0.0001 **) after TASH. Concentrations remained elevated at 60' (54.8 (31.6-118.3) RU/mL; adjusted p = 0.0019 *), returned to baseline at 2 h (30.9 (20-71.2) RU/mL; adjusted p = 1.0 vs. baseline) and decreased significantly below baseline at 4 h (24 (12.13-37.5) RU/mL, adjusted p = 0.0215 *). By 24 h, FGF23 had returned to baseline levels (28.8 (12.8-57.3) RU/mL; adjusted p = 1.0 vs. baseline). Although concentrations were numerically higher than at the 4 h nadir, this recovery did not reach statistical significance (adjusted p = 0.136 vs. 4 h). In STEMI patients, a non-significant decrease was observed from baseline (27 (15.5-35.75) RU/mL) to 3 h after recanalization (15.5 (6.75-34.25) RU/mL; p = 0.074, effect size r = 0.422). In an exploratory normalized analysis, the decline reached significance (p = 0.0241). CONCLUSIONS: The triphasic kinetics of circulating FGF23 in TASH patients-characterized by an early rise, transient undershoot, and a recovery toward baseline with a continuing upward trend-are consistent with a dynamic release-and-clearance pattern following myocardial injury. These findings are hypothesis-generating and warrant further investigation in larger cohorts with additional biomarkers to elucidate the source, regulation, and potential functional significance of FGF23 in the acute phase of myocardial infarction.

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