Clinica chimica acta; international journal of clinical chemistry · 2026
NT-IGFBP-4: A novel biomarker for risk prediction in acute heart failure.
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Li Ling, Wang Jing, Chen Chen, Wu Yu, Yang Juan, Shu Xin, Zhang Litao, Zhang Yi, Zhang Zhenlu
Аннотация
OBJECTIVES: Insulin-like growth factor binding protein-4 (IGFBP-4) fragments generated by PAPP-A-mediated proteolysis are emerging biomarkers of myocardial stress and remodeling. Although elevated N-terminal IGFBP-4 (NT-IGFBP-4) has been associated with heart failure (HF), its prognostic value remains unclear. This study evaluated the prognostic performance of NT-IGFBP-4, measured using a validated chemiluminescent immunoassay, in patients with acute heart failure (AHF) and compared it with the conventional biomarker NT-proBNP.
METHODS: A total of 309 patients with AHF were included. Baseline NT-IGFBP-4 and NT-proBNP were measured, and patients were followed for up to 1 year for HF rehospitalization and all-cause mortality. The prognostic performance of each biomarker and their combination for 30-day and 1-year outcomes was evaluated using ROC analysis, Kaplan-Meier analysis, and Cox proportional hazards regression with multivariable adjustment for clinical factors and the other biomarker. Optimal cut-off values were derived from ROC analysis.
RESULTS: During follow-up, 81 patients experienced clinical events, including 10 deaths and 71 hospital readmissions. NT-IGFBP-4 showed a moderate correlation with NT-proBNP, but only weak associations with hs-CRP and hs-cTnI. For 30-day outcomes, NT-IGFBP-4 remained independently predictive after mutual adjustment (HR = 10.07[3.10-32.68], p < 0.001), whereas NT-proBNP lost statistical significance under the same conditions (HR = 2.68[0.72-10.01], p = 0.142). For 1-year outcomes, both NT-IGFBP-4 (HR = 3.27[1.80-5.91], p < 0.001) and NT-proBNP (HR = 2.04[1.18-3.53], p = 0.010) remained independent predictors after adjustment for clinical covariates and each other. Notably, the combined assessment of both biomarkers further enhanced 1-year risk discrimination (HR = 5.72[2.73-11.98], p < 0.001).
CONCLUSIONS: NT-IGFBP-4 is a novel, independent prognostic biomarker in AHF, supporting its use in multimarker strategies for patient management.
METHODS: A total of 309 patients with AHF were included. Baseline NT-IGFBP-4 and NT-proBNP were measured, and patients were followed for up to 1 year for HF rehospitalization and all-cause mortality. The prognostic performance of each biomarker and their combination for 30-day and 1-year outcomes was evaluated using ROC analysis, Kaplan-Meier analysis, and Cox proportional hazards regression with multivariable adjustment for clinical factors and the other biomarker. Optimal cut-off values were derived from ROC analysis.
RESULTS: During follow-up, 81 patients experienced clinical events, including 10 deaths and 71 hospital readmissions. NT-IGFBP-4 showed a moderate correlation with NT-proBNP, but only weak associations with hs-CRP and hs-cTnI. For 30-day outcomes, NT-IGFBP-4 remained independently predictive after mutual adjustment (HR = 10.07[3.10-32.68], p < 0.001), whereas NT-proBNP lost statistical significance under the same conditions (HR = 2.68[0.72-10.01], p = 0.142). For 1-year outcomes, both NT-IGFBP-4 (HR = 3.27[1.80-5.91], p < 0.001) and NT-proBNP (HR = 2.04[1.18-3.53], p = 0.010) remained independent predictors after adjustment for clinical covariates and each other. Notably, the combined assessment of both biomarkers further enhanced 1-year risk discrimination (HR = 5.72[2.73-11.98], p < 0.001).
CONCLUSIONS: NT-IGFBP-4 is a novel, independent prognostic biomarker in AHF, supporting its use in multimarker strategies for patient management.