Jungbauer Carsten G, Riedlinger Julia, Block Dirk, Stadler Stefan, Birner Christoph, Buesing Monika, König Wolfgang, Riegger Günter, Maier Lars, Luchner Andreas
Department of Cardiology, Klinik & Poliklinik fuer Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
Biomark Med. 2014;8(6):777-89. doi: 10.2217/bmm.14.31.
As complex disease, heart failure is associated with various pathophysiological and biochemical disorders. No single biomarker is able to display all these characteristics. Therefore, we evaluated a multimarker panel together with the biochemical gold-standard NT-proBNP. Part of the panel are markers for angiogenesis (Endostatin, IBP-4, IBP-7, sFlt-1 as antiangiogenetic factors and PLGF as angiogenectic factor), myocyte stress (GDF-15), extracellular matrix remodelling (galectin-3, mimecan and TIMP-1), inflammation (galectin-3) and myocyte injury (hs-TnT).
All markers (Roche Diagnostics, Penzberg, Germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls.
All markers were positively correlated with ln NT-proBNP (each p < 0.05). Furthermore, they were significantly elevated in patients with chronic heart failure (each p < 0.05). All markers increased significantly with severity of LV dysfunction and severity of New York Heart Association class (each p < 0.05), except for PLGF and Mimecan (each p = NS). With the exception of endostatin, mimecan and PLGF, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. In a multimarker approach of the five biomarkers with the best performance (NT-proBNP, hs-TnT, TIMP-1, GDF-15 and IBP-4), the event rate was superior to NT-proBNP alone and increased significantly and progressively with the number of elevated biomarkers.
All emerging markers increased stepwise with the severity of symptoms and LV dysfunction and offer important prognostic information in chronic heart failure, except for PLGF and mimecan. Five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. Prognostication in heart failure may be further improved through a multimarker approach.
作为一种复杂疾病，心力衰竭与多种病理生理和生化紊乱相关。没有单一生物标志物能够展现所有这些特征。因此，我们评估了一个多标志物组合以及生化金标准NT-proBNP。该组合的部分标志物包括血管生成标志物（内皮抑素、IBP-4、IBP-7、sFlt-1作为抗血管生成因子，胎盘生长因子作为血管生成因子）、心肌细胞应激标志物（生长分化因子-15）、细胞外基质重塑标志物（半乳糖凝集素-3、骨膜蛋白和基质金属蛋白酶组织抑制因子-1）、炎症标志物（半乳糖凝集素-3）和心肌细胞损伤标志物（高敏肌钙蛋白T）。
在149例慢性心力衰竭患者和84例健康对照者组成的队列中评估所有标志物（德国彭茨贝格罗氏诊断公司）。
所有标志物均与NT-proBNP的自然对数呈正相关（均p<0.05）。此外，它们在慢性心力衰竭患者中显著升高（均p<0.05）。除胎盘生长因子和骨膜蛋白外（均p=无显著性差异），所有标志物均随左心室功能障碍严重程度和纽约心脏协会分级严重程度显著升高（均p<0.05）。除内皮抑素、骨膜蛋白和胎盘生长因子外，所有其他标志物在3年随访中均是全因死亡率的进一步显著预测指标。在对表现最佳的五种生物标志物（NT-proBNP、高敏肌钙蛋白T、基质金属蛋白酶组织抑制因子-1、生长分化因子-15和IBP-4）进行多标志物分析时，事件发生率优于单独使用NT-proBNP，且随着升高的生物标志物数量显著且逐步增加。
除胎盘生长因子和骨膜蛋白外，所有新出现的标志物均随症状严重程度和左心室功能障碍程度逐步升高，并在慢性心力衰竭中提供重要的预后信息。五种具有不同病理生理背景的生物标志物在心力衰竭中具有附加的预后价值。通过多标志物方法可能进一步改善心力衰竭的预后评估。
