Keeley Ellen C, Schutt Robert C, Marinescu Mark A, Burdick Marie D, Strieter Robert M, Mehrad Borna
Department of Medicine, University of Virginia, Charlottesville, Va; Division of Cardiology, University of Virginia, Charlottesville, Va.
Houston Methodist DeBakey Heart & Vascular Center, Houston, Tex.
Transl Res. 2016 Jun;172:73-83.e1. doi: 10.1016/j.trsl.2016.02.013. Epub 2016 Mar 8.
Half of the patients who present with unstable angina (UA) develop recurrent symptoms over the subsequent year. Identification of patients destined to develop such adverse events would be clinically valuable, but current tools do not allow for this discrimination. Fibrocytes are bone marrow-derived progenitor cells that co-express markers of leukocytes and fibroblasts and are released into the circulation in the context of tissue injury. We hypothesized that, in patients with UA, the number of circulating fibrocytes predicts subsequent adverse events. We enrolled 55 subjects with UA, 18 with chronic stable angina, and 22 controls and correlated their concentration of circulating fibrocytes to clinical events (recurrent angina, myocardial infarction, revascularization, or death) over the subsequent year. Subjects with UA had a >2-fold higher median concentration of both total and activated fibrocytes compared with subjects with chronic stable angina and controls. In UA subjects, the concentration of total fibrocytes identified those who developed recurrent angina requiring revascularization (time-dependent area under the curve 0.85) and was superior to risk stratification using thrombolysis in myocardial infarction risk score and N-terminal pro B-type natriuretic peptide levels (area under the curve, 0.53 and 0.56, respectively, P < 0.001). After multivariable adjustment for thrombolysis in myocardial infarction predicted death, MI, or recurrent ischemia, total fibrocyte level was associated with recurrent angina (hazard ratio, 1.016 per 10,000 cells/mL increase; 95% confidence interval, 1.007-1.024; P < 0.001). Circulating fibrocytes are elevated in patients with UA and successfully risk stratify them for adverse clinical outcomes. Fibrocytes may represent a novel biomarker of outcome in this population.
出现不稳定型心绞痛(UA)的患者中有一半会在随后一年出现复发症状。识别那些注定会发生此类不良事件的患者具有临床价值,但目前的工具无法进行这种区分。纤维细胞是源自骨髓的祖细胞,共表达白细胞和成纤维细胞的标志物,并在组织损伤的情况下释放到循环中。我们假设,在UA患者中,循环纤维细胞的数量可预测随后的不良事件。我们纳入了55例UA患者、18例慢性稳定型心绞痛患者和22例对照,并将他们循环纤维细胞的浓度与随后一年的临床事件(复发性心绞痛、心肌梗死、血运重建或死亡)进行关联分析。与慢性稳定型心绞痛患者和对照相比,UA患者的总纤维细胞和活化纤维细胞的中位浓度高出两倍以上。在UA患者中,总纤维细胞的浓度可识别出那些发生需要血运重建的复发性心绞痛的患者(曲线下时间依赖性面积为0.85),并且优于使用心肌梗死溶栓风险评分和N末端B型利钠肽前体水平进行的风险分层(曲线下面积分别为0.53和0.56,P<0.001)。在对心肌梗死溶栓预测死亡、心肌梗死或复发性缺血进行多变量调整后,总纤维细胞水平与复发性心绞痛相关(风险比,每增加10,000个细胞/mL为1.016;95%置信区间,1.007 - 1.024;P<0.001)。UA患者的循环纤维细胞水平升高,并成功地对他们进行了不良临床结局的风险分层。纤维细胞可能代表了该人群中一种新的结局生物标志物。