Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eur J Heart Fail. 2017 Aug;19(8):1001-1010. doi: 10.1002/ejhf.749. Epub 2017 Jan 30.
We evaluated the added prognostic value of a multi-time point-based multimarker panel of biomarkers in patients with acute heart failure (AHF).
Seven circulating biomarkers [NT-proBNP, high sensitivity cardiac troponin T (hs-cTnT), soluble ST2 (sST2), growth differentiation factor 15 (GDF-15), cystatin-C, galectin-3, and high sensitivity C-reactive protein (hs-CRP)] were measured at baseline and on days 2, 5, 14, and 60 in 1161 patients enrolled in the RELAX-AHF trial. Patients with BNP ≥350 ng/L or NT-proBNP ≥1400 ng/L, mild to moderate renal impairment, and systolic blood pressure >125 mmHg were included in the trial. Time-dependent Cox regression analysis was utilized to evaluate the incremental value of serial measurement of biomarkers. Added value of individual biomarkers and their combination, on top of a pre-specified baseline model, was quantified with the gain in the C-index. Serial biomarker evaluation showed incremental predictive value over baseline measurements alone for the prediction of 180-day cardiovascular mortality except for galectin-3. While a repeat measurement as early as day 2 was adequate for NT-proBNP and cystatin-C in terms of maximizing discriminatory accuracy, further measurements on days 14 and 60 provided added value for hs-cTnT, GDF-15, sST2, and hs-CRP. Individual biomarker additions on top of the baseline model showed additional prognostic value. The greatest prognostic gain was, however, attained with the combination of NT-proBNP, hs-cTnT, GDF-15, and sST2, which yielded 0.08 unit absolute increment in the C-index to 0.87 (95% confidence interval 0.83-0.91].
In patients with AHF and mild to moderate renal impairment, a multimarker approach based on a panel of serially evaluated biomarkers provides the greatest prognostic improvement unmatched by a single time point-based single marker strategy.
我们评估了基于多时间点的多标志物生物标志物panel 在急性心力衰竭（AHF）患者中的预后价值。
在 RELAX-AHF 试验中，共纳入 1161 例患者，分别在基线及第 2、5、14 和 60 天检测了 7 种循环生物标志物[NT-proBNP、高敏心肌肌钙蛋白 T（hs-cTnT）、可溶性 ST2（sST2）、生长分化因子 15（GDF-15）、胱抑素-C、半乳糖凝集素-3 和高敏 C 反应蛋白（hs-CRP）]。入选患者的 BNP≥350ng/L 或 NT-proBNP≥1400ng/L，轻度至中度肾功能不全和收缩压＞125mmHg。采用时间依赖性 Cox 回归分析评估生物标志物连续测量的增量价值。通过增加 C 指数，定量评估了个体标志物及其组合在预设基线模型基础上的附加价值。与基线测量相比，生物标志物的连续评估除半乳糖凝集素-3外，对 180 天心血管死亡率的预测均具有增量预测价值。尽管仅在第 2 天进行重复测量就足以最大限度地提高 NT-proBNP 和胱抑素-C 的区分准确性，但在第 14 和 60 天进一步测量 hs-cTnT、GDF-15、sST2 和 hs-CRP 可提供附加价值。在基线模型的基础上增加单个标志物的测量显示出额外的预后价值。然而，最大的预后增益是通过 NT-proBNP、hs-cTnT、GDF-15 和 sST2 的组合获得的，这使 C 指数的绝对值增加了 0.08 个单位，达到 0.87（95%置信区间 0.83-0.91）。
在伴有轻度至中度肾功能不全的 AHF 患者中，基于连续评估的多标志物方法比基于单个时间点的单个标志物策略提供了最大的预后改善。
