Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
The Danish Diabetes Academy, Odense, Denmark.
J Am Heart Assoc. 2017 Mar 17;6(3):e005358. doi: 10.1161/JAHA.116.005358.
Fragments of insulin-like growth factor binding protein 4 (IGFBP-4) are potential new biomarkers for cardiac risk assessment. The fragments are generated on specific cleavage by pregnancy-associated plasma protein-A, which exerts proatherogenic activity. This study investigated the prognostic value of IGFBP-4 fragments in patients with ST-segment elevation myocardial infarction.
We prospectively included 656 patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn before percutaneous coronary intervention, and levels of intact IGFBP-4 and N-terminal and C-terminal IGFBP-4 fragments were measured by specific assays. End points were 5-year all-cause and cardiovascular mortality and the combined end point of major adverse cardiac events. Prognostic potential was evaluated on top of a clinical model in terms of discrimination, calibration, and reclassification analysis. During follow-up, 166 patients experienced a major adverse cardiac event and 136 patients died, of whom 69 died from cardiovascular causes. Both IGFBP-4 fragments were associated with all end points (<0.001). After multivariable adjustments, both N-terminal and C-terminal IGFBP-4 fragment levels remained associated with all end points, including cardiovascular mortality with hazard ratios per doubling in protein concentration of 2.54 (95% CI 1.59-4.07; <0.001) and 2.07 (95% CI 1.41-3.04; <0.001), respectively. Incorporation of IGFBP-4 fragments into a clinical model with 15 risk factors improved C-statistics and model calibration and provided incremental prognostic contribution, as assessed by net reclassification improvement and integrated discrimination improvement.
IGFBP-4 fragments are associated with increased risk of all-cause mortality, cardiovascular mortality, and major adverse cardiac events in patients with ST-segment elevation myocardial infarction.
胰岛素样生长因子结合蛋白 4（IGFBP-4）的片段是心脏风险评估的潜在新生物标志物。这些片段是通过妊娠相关血浆蛋白 A 的特异性切割产生的，而妊娠相关血浆蛋白 A 具有促动脉粥样硬化活性。本研究调查了 IGFBP-4 片段在 ST 段抬高型心肌梗死患者中的预后价值。
我们前瞻性纳入了 2006 年 9 月至 2008 年 12 月接受经皮冠状动脉介入治疗的 656 例 ST 段抬高型心肌梗死患者。在经皮冠状动脉介入治疗前采集血样，并通过特定的检测方法测量完整 IGFBP-4 以及 N 端和 C 端 IGFBP-4 片段的水平。终点是 5 年全因和心血管死亡率以及主要不良心脏事件的联合终点。在考虑临床模型的基础上，通过判别分析、校准分析和重新分类分析评估预后潜力。在随访期间，166 例患者发生主要不良心脏事件，136 例患者死亡，其中 69 例死于心血管原因。IGFBP-4 片段均与所有终点相关（<0.001）。在多变量调整后，N 端和 C 端 IGFBP-4 片段水平仍与所有终点相关，包括心血管死亡率，其蛋白浓度每增加一倍的风险比分别为 2.54（95%CI 1.59-4.07；<0.001）和 2.07（95%CI 1.41-3.04；<0.001）。将 IGFBP-4 片段纳入包含 15 个危险因素的临床模型可提高 C 统计量和模型校准度，并通过净重新分类改善和综合判别改善评估提供增量预后贡献。
IGFBP-4 片段与 ST 段抬高型心肌梗死患者的全因死亡率、心血管死亡率和主要不良心脏事件风险增加相关。
