NT-IGFBP-4：一种用于急性心力衰竭风险预测的新型生物标志物

摘要(中文译文)

※ 中文译文由 AI 辅助生成,仅供学术参考,请以英文原文为准。

PAPP-A介导的蛋白水解产生的胰岛素样生长因子结合蛋白-4（IGFBP-4）片段是心肌应激和重塑的新兴生物标志物。尽管N-末端IGFBP-4（NT-IGFBP-4）升高与心力衰竭（HF）有关，但其预后价值尚不清楚。本研究评估了使用经过验证的化学发光免疫测定法测量的NT-IGFBP-4在急性心力衰竭（AHF）患者中的预后表现，并将其与常规生物标志物NT-proBNP进行了比较。共纳入309名AHF患者。测量基线NT-IGFBP-4和NT-proBNP，并对患者进行长达1年的HF再住院和全因死亡率随访。使用ROC分析、Kaplan-Meier分析和Cox比例风险回归，对临床因素和其他生物标志物进行多变量调整，评估每种生物标志物及其组合对30天和1年结果的预后表现。ROC分析得出了最佳临界值。在随访期间，81名患者出现了临床事件，包括10例死亡和71例再次入院。NT-IGFBP-4与NT-proBNP呈中度相关，但与hs-CRP和hs-cTnI的相关性较弱。对于30天的结果，NT-IGFBP-4在相互调整后仍具有独立预测性（HR=10.07[3.10-32.68]，p<0.001），而NT-proBNP在相同条件下失去了统计学意义（HR=2.68[0.72-10.01]，p=0.142）。对于1年的结果，NT-IGFBP-4（HR=3.27[1.80-5.91]，p<0.001）和NT-proBNP（HR=2.04[1.18-3.53]，p=0.010）在调整临床协变量和彼此后仍然是独立的预测因素。值得注意的是，对这两种生物标志物的联合评估进一步增强了1年风险鉴别（HR=5.72[2.73-11.98]，p<0.001）。NT-IGFBP-4是AHF中一种新的独立预后生物标志物，支持其在患者管理的多标志物策略中的使用。

Abstract

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. 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. 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). NT-IGFBP-4 is a novel, independent prognostic biomarker in AHF, supporting its use in multimarker strategies for patient management.

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