Department of Cardiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Int J Cardiol. 2013 Sep 30;168(2):1251-7. doi: 10.1016/j.ijcard.2012.11.052. Epub 2012 Dec 4.
Accurate risk prediction is important for an adequate management of heart failure (HF) patients. We assessed the incremental prognostic ability of a multi-biomarker approach in advanced HF.
In 349 patients with advanced HF (median 75 years, 66% male) we investigated the incremental prognostic value of 12 novel biomarkers involved in different pathophysiological pathways including inflammation, immunological activation, oxidative stress, cell growth, remodeling, angiogenesis and apoptosis.
During a median follow-up of 4.9 years 55.9% of patients died. Using multivariable Cox regression and bootstrap variable-selection age, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the following 5 novel biomarkers were retained in the best mortality prediction model: the chemokine fractalkine, the angiogenic and mitogenic hepatocyte growth factor (HGF), the growth differentiation factor 15 (GDF-15) influencing cardiac remodeling and apoptosis, and the 2 pro-apoptotic molecules soluble apoptosis-stimulating fragment (sFAS) and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL). This multi-biomarker score had strong discriminatory power for 5-year mortality (area under the Receiver Operating Characteristic curve [AUC]=0.81) and improved risk prediction beyond the prognostic power of a comprehensive conventional risk score including known clinical predictors and NT-proBNP (AUC=0.77). Net reclassification confirmed a significant improvement of individual risk prediction (p=0.003).
Risk prediction by a multi-biomarker score is superior to a conventional risk score including clinical parameters and NT-proBNP. Additional predictive information from different biological pathways reflects the multisystemic character of HF.
准确的风险预测对于心力衰竭（HF）患者的充分管理非常重要。我们评估了多生物标志物方法在晚期 HF 中的增量预后能力。
在 349 名患有晚期 HF 的患者（中位数年龄 75 岁，66%为男性）中，我们研究了涉及不同病理生理途径的 12 种新型生物标志物的增量预后价值，包括炎症、免疫激活、氧化应激、细胞生长、重塑、血管生成和细胞凋亡。
在中位随访 4.9 年期间，55.9%的患者死亡。使用多变量 Cox 回归和引导变量选择，年龄、慢性阻塞性肺疾病、N 末端 pro-B 型利钠肽（NT-proBNP）和以下 5 种新型生物标志物保留在最佳死亡率预测模型中：趋化因子 fractalkine、血管生成和有丝分裂原肝细胞生长因子（HGF）、生长分化因子 15（GDF-15）影响心脏重塑和细胞凋亡，以及 2 种促凋亡分子可溶性凋亡刺激片段（sFAS）和可溶性肿瘤坏死因子相关凋亡诱导配体（sTRAIL）。该多生物标志物评分对 5 年死亡率具有很强的区分能力（Receiver Operating Characteristic 曲线下面积[AUC] = 0.81），并改善了风险预测，超过了包括已知临床预测因子和 NT-proBNP 的综合常规风险评分的预后能力（AUC = 0.77）。净重新分类证实了个体风险预测的显著改善（p = 0.003）。
多生物标志物评分的风险预测优于包括临床参数和 NT-proBNP 的常规风险评分。来自不同生物途径的额外预测信息反映了 HF 的多系统特征。
