单核细胞趋化蛋白-1：又一个急性冠脉综合征预后的生物标志物

Serial Measurement of Monocyte Chemoattractant Protein-1 After Acute Coronary Syndromes
连续测定急性冠状动脉综合征患者的单核细胞趋化蛋白1水平
Results From the A to Z Trial
本结果来自于从替罗非班到辛伐他汀研究（A to Z Trial）
Objectives: This study sought to determine whether the novel biomarker monocyte chemoattractant protein (MCP)-1 adds prognostic value to standard risk assessment tools and biomarkers after acute coronary syndromes (ACS).
目的：力图确定对于急性冠状动脉综合征患者，单核细胞趋化蛋白1是否是一种新的生物标记；以及它除了具有标准的风险评估作用外，是否还能提示预后。
Background: Monocyte chemoattractant protein-1 is a chemokine recruiting signal for monocytes that may function as both a mediator and biomarker of ACS.
研究背景：单核细胞趋化蛋白1是一种对单核细胞发出募集信号的趋化因子，它可能既是急性冠状动脉综合征的介导因子，也是该综合征的生物标记。
Methods: Monocyte chemoattractant protein-1 was measured at baseline (n = 4,244), 4 months (n = 3,603), and 12 months (n = 2,950), and correlated with clinical events in the Z phase of the A to Z (Aggrastat to Zocor) trial, which compared early intensive versus delayed and less intensive statin therapy after ACS.
方法：对从替罗非班到辛伐他汀研究（A to Z Trial）中的Z期研究对象进行连续测定单核细胞趋化蛋白1水平，测定时点分别为基线(n = 4,244), 发病后4月 (n = 3,603), 发病后一年(n = 2,950)，并同临床事件作相关分析。Z期研究是对急性冠状动脉综合征患者分别进行早期积极的他汀类治疗或者延迟并相对低剂量的他汀类治疗，最终比较两种治疗方案孰优孰劣。
Results: Rates of death and the composite end points of death or myocardial infarction (MI); death, MI, or heart failure; and cardiovascular death, MI, readmission for ACS, or stroke increased across baseline quartiles of MCP-1 and among patients with MCP-1 greater than versus less than or equal to the pre-specified threshold of 238 pg/ml (p < 0.01 for each). After adjustment for standard risk predictors and levels of C-reactive protein and B-type natriuretic peptide, MCP-1 >238 pg/ml remained independently associated with mortality (hazard ratio 2.16; 95% confidence interval 1.54 to 3.02) and with each composite end point, and increased the C-statistic of the fully adjusted mortality model from 0.76 to 0.78 (p < 0.0001). A value of MCP-1 >238 pg/ml at the 4-month follow-up visit was also independently associated with mortality after 4 months (hazard ratio 1.76; 95% confidence interval 1.12 to 2.76). Elevated MCP-1 levels did not identify patients who derived incremental benefit from intensive statin therapy.
结果：当单核细胞趋化蛋白1水平超过基线四分位时，急性冠状动脉综合征患者的死亡率、死亡或心肌梗死的复合终点（死亡，心肌梗死，心衰）以及心血管死亡事件、心肌梗死事件、急性冠状动脉综合征再次入院或中风可能性均上升。并且该蛋白水平不小于特定阈值（238 pg/ml）时，以上事件发生率明显提高（各项P值均小于0.01）。经C反应蛋白与B型利钠肽水平调整后，单核细胞趋化蛋白1大于238 pg/ml仍与死亡率独立相关(危害比为2.16，95%可信区间为1.54至3.02之间)。并且对于每一个复合终点，完全调正死亡率的C值由0.76增至0.78（P值小于0.0001）。在发病后第四个月随访时所测得的单核细胞趋化蛋白1水平，如果大于238 pg/ml，则与四月后的死亡率独立相关（危害比为1.76，95%可信区间为1.12至2.76之间）。对于那些接受积极的他汀类药物治疗方案的患者，上升的单核细胞趋化蛋白1水平不能确定其是否获得益处。
Conclusions: Monocyte chemoattractant protein-1 provides independent prognostic value in the acute and chronic phases after ACS and merits further evaluation as a prognostic marker and potential therapeutic target.
结论：在急性冠状动脉综合征急慢性期内，单核细胞趋化蛋白1具有独立的评估预后价值，它可能是一种预后标记物以及潜在的治疗靶点，有待更深入的研究。