Aims We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. Methods and results Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. Conclusion Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

中文翻译：

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富含半胱氨酸的血管生成诱导剂 61 (Cyr61)：一种新型的急性心肌损伤可溶性生物标志物可改善急性冠状动脉综合征后的风险分层

目的 我们旨在确定一种与导致急性冠状动脉综合征 (ACS) 的早期事件有关的新型生物标志物，并评估其在诊断和风险分层中的作用。方法和结果 生物标志物鉴定基于基因表达谱。在 ACS 患者的冠状动脉血栓中，与外周单核细胞相比，富含半胱氨酸的血管生成诱导物 61 (Cyr61, CCN1) 基因转录物高度上调。在小鼠缺血再灌注模型 (I/R) 中，与对照组相比，心肌 Cyr61 的表达显着增加。使用酶联免疫吸附测定法测定人血清中的 Cyr61 水平。ACS 队列 (n = 2168) 转诊进行冠状动脉造影、稳定型冠状动脉疾病 (CAD) (n = 53)、和肥厚型梗阻性心肌病 (HOCM) 患者 (n = 15) 用于识别和评估生物标志物的诊断和预后性能。与非 ST 段抬高心肌梗死/不稳定型心绞痛或稳定型 CAD 患者相比，ST 段抬高心肌梗死患者的 Cyr61 显着升高，无论是否存在冠状动脉血栓。在接受室间隔肥大的经冠状动脉消融术的 HOCM 患者中，在间隔分支闭塞后，Cyr61 迅速释放。当在 30 天（C 统计量 0.88 至 0.89，P = 0.001）和 1 年（C 统计量 0.77 至 0.80，P < 0.001）与高-敏感性肌钙蛋白 T（30 天：0.88 至 0.89，P < 0.001；1 年：0.77 至 0.79，P < 0.001）。对于全因死亡率或心肌梗死的复合终点，也获得了类似的结果。相反，在基于人群的病例对照队列（n = 362）中，Cyr61 与不良结果无关。结论 Cyr61 是一种新的反映心肌损伤的早期生物标志物，可改善 ACS 患者的风险分层。