Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, the Netherlands (MT.G., L.C.v.V., I.K., K.M.A., O.C.M., E.B.).
Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, the Netherlands (S.J.B.).
Circ Heart Fail. 2023 Jan;16(1):e009526. doi: 10.1161/CIRCHEARTFAILURE.122.009526. Epub 2022 Nov 21.
Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk.
TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling.
Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785).
Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice.
URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).
关于急性心力衰竭（HF）中连续测量生长分化因子 15（GDF-15）的研究有限。此外，有几个病理生理途径导致 HF。因此，我们旨在通过多标志物方法探索连续测量 GDF-15 的（附加）预后价值，以更准确地预测 HF 风险。
TRIUMPH（用于管理心力衰竭患者的独特和新颖策略的转化倡议）是一项前瞻性队列研究，纳入了 2009 年至 2014 年期间荷兰 14 家医院的 496 名急性 HF 患者。在 1 年的随访期间，安排了 7 次采血。在中央实验室测量 GDF-15、NT-proBNP（N 末端 pro-B 型利钠肽）、ST2（肿瘤抑制物 2）、半乳糖凝集素-3、肌钙蛋白 I 和肌酐。我们使用多变量联合建模，将这些生物标志物的重复测量与全因死亡率和 HF 再住院的复合主要终点相关联。
中位年龄为 74 岁，37%为女性。中位基线 GDF-15 为 4632 pg/mL。188 例（40%）患者达到主要终点。主要终点前几周，平均估计 GDF-15 水平升高。每 1 SD 差异的 GDF-15 对数的危险比为 2.14（95%CI，1.78-2.57），未经调整，调整临床混杂因素后为 1.96（1.49-2.53），联合所有生物标志物共同建模后为 1.44（1.05-1.91）。NT-proBNP 的调整 HR 分别为 2.38（1.78-3.33）和 1.52（1.15-2.08）。结合 GDF-15、NT-proBNP 和肌钙蛋白 I 的多标志物模型提供了有利的风险分层（曲线下面积=0.785）。
连续测量的 GDF-15 可独立且动态地预测急性 HF 指数入院后 1 年随访期间不良结局的风险。NT-proBNP 仍然是潜在候选者中的强大预测因子。在临床实践中，应考虑多种生物标志物进行分层。
网址：https://www.trialregister.nl/trial/1783；唯一标识符：NTR1893。（该试验暂时可在 https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893. 找到。）
