Guo Yutao, Apostalakis Stavros, Blann Andrew D, Lip Gregory Y H
Haemostasis, Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.
Cerebrovasc Dis. 2014;38(3):204-11. doi: 10.1159/000365841. Epub 2014 Oct 9.
There is growing evidence that chemokines are potentially important mediators of the pathogenesis of atherosclerotic disease. Major atherothrombotic complications, such as stroke and myocardial infarction, are common among atrial fibrillation (AF) patients. This increase in risk of adverse events may be predicted by a score based on the presence of certain clinical features of chronic heart failure, hypertension, age 75 years or greater, diabetes and stroke (the CHADS2 score). Our objective was to assess the prognostic value of plasma chemokines CCL2, CXCL4 and CX3CL1, and their relationship with the CHADS2 score, in AF patients.
Plasma CCL2, CXCL4 and CX3CL1 were measured in 441 patients (59% male, mean age 75 years, 12% paroxysmal, 99% on warfarin) with AF. Baseline clinical and demographic factors were used to define each subject's CHADS2 score. Patients were followed up for a mean 2.1 years, and major adverse cardiovascular and cerebrovascular events (MACCE) were sought, being the combination of cardiovascular death, acute coronary events, stroke and systemic embolism.
Fifty-five of the AF patients suffered a MACCE (6% per year). Those in the lowest CX3CL1 quartile (≤ 0.24 ng/ml) had fewest MACCE (p = 0.02). In the Cox regression analysis, CX3CL1 levels >0.24 ng/ml (Hazard ratio 2.8, 95% CI 1.02-8.2, p = 0.045) and age (p = 0.042) were independently linked with adverse outcomes. The CX3CL1 levels rose directly with the CHADS2 risk score (p = 0.009). The addition of CX3CL1 did not significantly increased the discriminatory ability of the CHADS2 clinical factor-based risk stratification (c-index 0.60 for CHADS2 alone versus 0.67 for CHADS2 plus CX3CL1 >0.24 ng/ml, p = 0.1). Aspirin use was associated with lower levels of CX3CL1 (p = 0.0002) and diabetes with higher levels (p = 0.031). There was no association between CXCL4 and CCL2 plasma levels and outcomes.
There is an independent association between low plasma CX3CL1 levels and low risk of major cardiovascular events in AF patients, as well as a linear association between CX3CL1 plasma levels and CHADS2-defined cardiovascular risk. The potential for CX3CL1 in refining risk stratification in AF patients merits consideration.
越来越多的证据表明趋化因子可能是动脉粥样硬化性疾病发病机制中潜在的重要介质。主要的动脉粥样硬化血栓形成并发症，如中风和心肌梗死，在心房颤动（AF）患者中很常见。基于慢性心力衰竭、高血压、75岁及以上年龄、糖尿病和中风等某些临床特征（CHADS2评分）的评分可能预测不良事件风险的增加。我们的目的是评估血浆趋化因子CCL2、CXCL4和CX3CL1在AF患者中的预后价值及其与CHADS2评分的关系。
测定了441例AF患者（59%为男性，平均年龄75岁，12%为阵发性，99%服用华法林）的血浆CCL2、CXCL4和CX3CL1。使用基线临床和人口统计学因素来确定每个受试者的CHADS2评分。对患者进行了平均2.1年的随访，并追踪主要不良心血管和脑血管事件（MACCE），即心血管死亡、急性冠状动脉事件、中风和全身性栓塞的综合情况。
55例AF患者发生了MACCE（每年6%）。CX3CL1四分位数最低（≤0.24 ng/ml）的患者发生MACCE的情况最少（p = 0.02）。在Cox回归分析中，CX3CL1水平>0.24 ng/ml（风险比2.8，95%可信区间1.02 - 8.2，p = 0.045）和年龄（p = 0.042）与不良结局独立相关。CX3CL1水平随CHADS2风险评分直接升高（p = 0.009）。添加CX3CL1并未显著提高基于CHADS2临床因素的风险分层的辨别能力（单独CHADS2的c指数为0.60，CHADS2加上CX3CL1>0.24 ng/ml时为0.67，p = 0.1）。使用阿司匹林与较低的CX3CL1水平相关（p = 0.0002），糖尿病与较高的CX水平相关（p = 0.031）。血浆CXCL4和CCL2水平与结局之间无关联。
AF患者血浆CX3CL1水平低与主要心血管事件风险低之间存在独立关联，且CX3CL1血浆水平与CHADS2定义的心血管风险之间存在线性关联。CX3CL1在完善AF患者风险分层方面的潜力值得考虑。
