Data_Sheet_1_Plasma Big Endothelin-1 Level Predicted 5-Year Major Adverse Cardiovascular Events in Patients With Coronary Artery Ectasia.docx

Background: Coronary artery ectasia (CAE) is found in about 1% of coronary angiography and is associated with poor clinical outcomes. The prognostic value of plasma big Endothelin-1 (ET-1) in CAE remains unknown.
Methods: Patients with angiographically confirmed CAE from 2009 to 2015, who had big ET-1 data available were included. The primary outcome was 5-year major adverse cardiovascular events (MACE), defined as a component of cardiovascular death and non-fatal myocardial infarction (MI). Patients were divided into high or low big ET-1 groups using a cut-off value of 0.58 pmol/L, according to the receiver operating characteristic curve. Kaplan-Meier method, propensity score method, and Cox regression were used to assess the clinical outcomes in the 2 groups.
Results: A total of 992 patients were included, with 260 in the high big ET-1 group and 732 in the low big ET-1 group. At 5-year follow-up, 57 MACEs were observed. Kaplan-Meier analysis and univariable Cox regression showed that patients with high big ET-1 levels were at increased risk of MACE (9.87 vs. 4.50%; HR 2.23, 95% CI 1.32–3.78, P = 0.003), cardiovascular death (4.01 vs. 1.69%; HR 2.37, 95% CI 1.02–5.48, P = 0.044), and non-fatal MI (6.09 vs. 2.84%; HR 2.17, 95% CI 1.11–4.24, P = 0.023). A higher risk of MACE in the high big ET-1 group was consistent in the propensity score matched cohort and propensity score weighted analysis. In multivariable analysis, a high plasma big ET-1 level was still an independent predictor of MACE (HR 1.82, 95% CI 1.02–3.25, P = 0.043). A combination of high plasma big ET-1 concentrate and diffuse dilation, when used to predict 5-year MACE risk, yielded a C-statistic of 0.67 (95% CI 0.59–0.74).
Conclusion: Among patients with CAE, high plasma big ET-1 level was associated with increased risk of MACE, a finding that could improve risk stratification.

背景：冠状动脉扩张症（Coronary artery ectasia, CAE）在约1%的冠状动脉造影术中被检出，且与不良临床结局相关。血浆大内皮素-1（big Endothelin-1, ET-1）在冠状动脉扩张症中的预后价值目前仍不明确。
方法：纳入2009年至2015年间经冠状动脉造影确诊且具备大内皮素-1检测数据的冠状动脉扩张症患者。本研究的主要结局为5年主要不良心血管事件（major adverse cardiovascular events, MACE），其定义为心血管死亡与非致命性心肌梗死（myocardial infarction, MI）的复合终点。依据受试者工作特征曲线（receiver operating characteristic curve），以0.58 pmol/L作为截断值将患者分为高、低大内皮素-1水平组。采用卡普兰-迈耶法（Kaplan-Meier method）、倾向得分法（propensity score method）及考克斯回归（Cox regression）评估两组患者的临床结局。
结果：本研究共纳入992例患者，其中高大内皮素-1水平组260例，低大内皮素-1水平组732例。在5年随访期间，共发生57例主要不良心血管事件。卡普兰-迈耶分析与单变量考克斯回归结果显示，高大内皮素-1水平患者的主要不良心血管事件风险显著升高（9.87% vs. 4.50%；风险比（Hazard Ratio, HR）2.23，95%置信区间（Confidence Interval, CI）1.32~3.78，P=0.003），心血管死亡风险（4.01% vs. 1.69%；HR 2.37，95%CI 1.02~5.48，P=0.044）及非致命性心肌梗死风险（6.09% vs. 2.84%；HR 2.17，95%CI 1.11~4.24，P=0.023）亦显著升高。在倾向得分匹配队列及倾向得分加权分析中，高大内皮素-1水平组的主要不良心血管事件高风险结果保持一致。多变量分析显示，血浆高浓度大内皮素-1仍是主要不良心血管事件的独立预测因素（HR 1.82，95%CI 1.02~3.25，P=0.043）。将血浆高浓度大内皮素-1与弥漫性扩张联合用于预测5年主要不良心血管事件风险时，其C统计量（C-statistic）为0.67（95%CI 0.59~0.74）。
结论：在冠状动脉扩张症患者中，血浆高浓度大内皮素-1水平与主要不良心血管事件风险升高相关，这一发现可用于优化患者的风险分层。