Department of Congenital Heart Disease and Paediatric Cardiology, German Heart Centre Munich, Technical University of Munich, Lazarettstraße 36, D-80636 Munich, Germany.
Institute of Laboratory Medicine, German Heart Centre Munich, Technical University of Munich, Munich, Germany.
Clin Chem Lab Med. 2020 Apr 18;58(9):1509-1516. doi: 10.1515/cclm-2019-1185. Print 2020 Aug 27.
NT-proBNP is one of the most important biomarkers for the diagnosis and risk assessment of heart failure in adults. Age- and gender-independent reference intervals (RIs) have been reported. In contrast, RIs in children are strongly age-dependent, do not exist for all ages and reveal a right-skewed distribution. Accordingly, no common Z-score can be formed and a cross-age interpretive method, so far, is missing.
Within the paper on hand, new evaluation techniques are applied to already published NT-proBNP study results and additionally to newly gained data. Upper limits (ULs), lower limits (LLs) and 50th percentiles are tested for power-like behavior as a function of age using linear regression analysis. Functions for continuous RIs are derived and reference limits are calculated on a per day basis. A corresponding Zlog formula is deduced and its usefulness is stated in two clinical examples.
The power-like behavior of NT-proBNP concentration from birth to 18 years is demonstrated. With age in days t and measured NT-proBNP value x in pg/mL, an age-specific Zlog value may directly be calculated using the equation:ZlogNT-proBNP=log x+0.512⋅log t-3.4171.489+0.014⋅log t⋅3.92${\rm{Zlo}}{{\rm{g}}_{{\rm{NT - proBNP}}}} = {{\log ;x + 0.512 \cdot \log ;t - 3.417} \over {1.489 + 0.014 \cdot \log ;t}} \cdot 3.92$.
Using formulas for UL and LL, continuous RIs from 0 to 18 years may be obtained. Continuity corresponds to physiological changes in the body much better than discrete RIs. With the advent of an NT-proBNP-specific Zlog value, a cross-age Z-score equivalent is providing an easy interpretation aid in everyday pediatric practice. This new approach allows to identify clinical worsening much better, sooner and more clearly than previous absolute values.
NT-proBNP 是诊断和评估成人心力衰竭风险的最重要生物标志物之一。已报道了与年龄和性别无关的参考区间（RI）。相比之下，儿童的 RI 强烈依赖于年龄，并非所有年龄段都有 RI，并且呈现右偏分布。因此，无法形成通用的 Z 分数，并且到目前为止，还缺少跨年龄的解释方法。
在本文中，应用新的评估技术对已发表的 NT-proBNP 研究结果以及新获得的数据进行评估。使用线性回归分析测试上限（UL）、下限（LL）和 50%分位数随年龄的幂律行为。推导用于连续 RI 的函数，并根据每天计算参考限。推导出相应的 Zlog 公式，并在两个临床实例中说明其有用性。
从出生到 18 岁，NT-proBNP 浓度的幂律行为得到证明。以年龄（t）和测量的 NT-proBNP 值（x），在 pg/mL 为单位，可直接使用以下方程计算特定年龄的 Zlog 值：ZlogNT-proBNP=log x+0.512⋅log t-3.4171.489+0.014⋅log t⋅3.92。ZlogNT-proBNP=log x+0.512 ⋅ log t-3.4171.489+0.014 ⋅ log t ⋅ 3.92。
使用 UL 和 LL 的公式，可以获得 0 至 18 岁的连续 RI。与离散 RI 相比，连续性更符合身体的生理变化。随着特定的 NT-proBNP 的 Zlog 值的出现，跨年龄的 Z 分数等效值为儿科日常实践提供了一种易于解释的辅助工具。与之前的绝对数值相比，这种新方法可以更好、更早且更清晰地识别临床恶化。
