Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Pulmonary Diseases, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Heart. 2020 Mar;106(6):467-473. doi: 10.1136/heartjnl-2019-315111. Epub 2019 Sep 6.
Despite its predictive value for mortality in various diseases, the relevance of growth differentiation factor-15 (GDF-15) as prognostic biomarker in pulmonary hypertension (PH) remains unclear. This study investigated the association between GDF-15 and outcomes in adults with PH.
This is a single-centre prospective observational cohort study. All adults with PH were included at the day of their diagnostic right heart catheterisation between 2012 and 2016. PH due to left heart disease was excluded. Venous blood sampling was performed and included GDF-15 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. Kaplan-Meier curves and Cox regression analysis were used to investigate the association between GDF-15 and a composite endpoint of death or lung transplantation. We adjusted for age and NT-proBNP in multivariable analysis. Reference values were established by GDF-15 measurements in healthy controls.
GDF-15 was measured in 103 patients (median age 59.2 years, 65% women, 51% pulmonary arterial hypertension). GDF-15 was elevated in 76 patients (74%). After a median follow-up of 3.4 (IQR 2.3-4.6) years, 32 patients (31.1%) reached the primary endpoint. Event-free survival 2 years after diagnosis was 100% in patients with normal GDF-15 versus 72.4% in patients with elevated GDF-15 (p=0.007). A significant association was found between GDF-15 and the primary endpoint (HR per twofold higher value 1.77, 95% CI 1.39 to 2.27, p<0.001), also after adjustment for age and NT-proBNP (HR 1.41, 95% CI 1.02 to 1.94, p=0.038).
High GDF-15 levels are associated with an increased risk of death or transplant in adults with PH, independent of age and NT-proBNP. As non-specific biomarker, GDF-15 could particularly be useful to detect low-risk patients.
尽管生长分化因子 15（GDF-15）对各种疾病的死亡率具有预测价值，但在肺动脉高压（PH）中，GDF-15 作为预后生物标志物的相关性仍不清楚。本研究旨在探讨 GDF-15 与成人 PH 患者结局之间的关系。
这是一项单中心前瞻性观察队列研究。所有在 2012 年至 2016 年期间接受诊断性右心导管检查当天的成人 PH 患者均被纳入研究。排除因左心疾病导致的 PH。进行静脉血采样，包括 GDF-15 和 N 末端 pro-B 型利钠肽（NT-proBNP）测量。使用 Kaplan-Meier 曲线和 Cox 回归分析来研究 GDF-15 与死亡或肺移植复合终点之间的关系。我们在多变量分析中调整了年龄和 NT-proBNP。通过健康对照者的 GDF-15 测量值建立参考值。
103 例患者（中位年龄 59.2 岁，65%为女性，51%为肺动脉高压）进行了 GDF-15 测量。76 例患者（74%）GDF-15 升高。中位随访 3.4（IQR 2.3-4.6）年后，32 例（31.1%）患者达到主要终点。诊断后 2 年无事件生存率，GDF-15 正常者为 100%，GDF-15 升高者为 72.4%（p=0.007）。GDF-15 与主要终点之间存在显著相关性（每两倍升高值的 HR 为 1.77，95%CI 为 1.39 至 2.27，p<0.001），即使在校正年龄和 NT-proBNP 后也是如此（HR 为 1.41，95%CI 为 1.02 至 1.94，p=0.038）。
在成人 PH 患者中，高 GDF-15 水平与死亡或移植风险增加相关，独立于年龄和 NT-proBNP。作为一种非特异性生物标志物，GDF-15 可能特别有助于检测低危患者。
