Department of Cardiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Department of Clinical Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Heart. 2019 Jul;105(13):999-1006. doi: 10.1136/heartjnl-2018-314168. Epub 2019 Jan 30.
Soluble suppression of tumourigenicity-2 (sST2) is upregulated as response to myocardial stress and may be a potential biomarker for risk stratification in patients with adult congenital heart disease (ACHD). This study aimed to investigate the release of sST2 and its association with cardiovascular events in ACHD.
In this prospective cohort study, 602 consecutive patients with ACHD visiting the outpatient clinic were included (2011-2013). The association between sST2 and a primary composite endpoint of all-cause mortality, heart failure, hospitalisation, arrhythmia, thromboembolic events or cardiac interventions was investigated using multivariable Cox regression.
sST2 was measured in 590 (98%) patients (median age 33 [25-41] years, 42% women). After a median follow-up of 5.8 [IQR 5.1-6.2) years, 225 (38.5%) reached the primary endpoint. sST2 was significantly associated with the primary endpoint when adjusted for age, sex, creatinine and N terminal pro-B type brain natriuretic peptide (NT-proBNP) (HR per twofold higher sST2: 1.28, 95% CI 1.03 to 1.58, p=0.025). This association negated when adjusted for clinical variables and NT-proBNP (HR per twofold higher sST2: 1.19, 95% CI 0.96 to 1.48, p=0.106). Stratified analysis in complex ACHD did show a significant association between sST2 and the primary endpoint when adjusted for clinical variables and NT-proBNP (HR per twofold higher sST2: 1.31, 95% CI 1.01 to 1.69, p=0.043). Sex-specific analysis showed an association between sST2 and the primary endpoint in women (HR per twofold higher sST2 1.80, 95% CI 1.30 to 2.49, p<0.001) but not in men (HR per twofold higher sST2 1.19, 95% CI 0.90 to 1.56, p=0.223).
sST2 is a promising novel biomarker in patients with ACHD, specifically in complex ACHD and women. Future research is warranted to elucidate sex-specific and diagnosis-specific differences.
可溶性抑制肿瘤发生-2（sST2）作为心肌应激的反应而上调，可能是成人先天性心脏病（ACHD）患者风险分层的潜在生物标志物。本研究旨在探讨 sST2 的释放及其与 ACHD 患者心血管事件的关系。
本前瞻性队列研究纳入了 602 例连续就诊的 ACHD 患者（2011-2013 年）。使用多变量 Cox 回归分析 sST2 与全因死亡率、心力衰竭、住院、心律失常、血栓栓塞事件或心脏介入治疗的主要复合终点之间的关系。
590 例（98%）患者测量了 sST2（中位年龄 33[25-41]岁，42%为女性）。中位随访 5.8[IQR 5.1-6.2]年后，225 例（38.5%）达到主要终点。调整年龄、性别、肌酐和 N 末端 pro-B 型脑利钠肽（NT-proBNP）后，sST2 与主要终点显著相关（每两倍 sST2 升高的 HR：1.28，95%CI 1.03-1.58，p=0.025）。当调整临床变量和 NT-proBNP 后，这种相关性消失（每两倍 sST2 升高的 HR：1.19，95%CI 0.96-1.48，p=0.106）。在复杂 ACHD 的分层分析中，当调整临床变量和 NT-proBNP 后，sST2 与主要终点之间仍存在显著相关性（每两倍 sST2 升高的 HR：1.31，95%CI 1.01-1.69，p=0.043）。性别特异性分析显示，sST2 与女性患者的主要终点之间存在相关性（每两倍 sST2 升高的 HR：1.80，95%CI 1.30-2.49，p<0.001），但在男性患者中无相关性（每两倍 sST2 升高的 HR：1.19，95%CI 0.90-1.56，p=0.223）。
sST2 是 ACHD 患者，特别是复杂 ACHD 和女性患者中有前途的新型生物标志物。需要进一步研究以阐明性别特异性和诊断特异性差异。
