急性冠脉综合征患者补体水平动态变化及与心肌损伤的关系

Dynamic changes of complement level in patients with acute coronary syndrome and its relationships with myocardial injury

目的探讨血清补体C3、C4、C5b-9水平与急性冠脉综合征（ACS）心肌损伤的关系。方法采用回顾性研究方法，选择2014年1月至2016年7月因缺血性胸痛或胸部不适12 h内收治于天津市人民医院心内科的170例ACS患者〔ST段抬高型心肌梗死（STEMI）110例，非ST段抬高型急性冠脉综合征（NSTE-ACS）60例〕，以同期36例健康体检者作为健康对照组。记录患者入院1、3、7 d血清补体C3、C4、C5b-9水平及心功能指标，随访1年的主要不良心血管事件（MACE）发生情况和再入院率。用Pearson相关分析法分析血清补体与心功能指标的相关性。结果① NSTE-ACS组和STEMI组发病1 d时血清补体C3、C4、C5b-9水平均显著高于健康对照组〔C3（g/L）：1.04±0.33、1.26±0.35比0.39±0.21，C4（g/L）：0.31±0.14、0.33±0.10比0.19±0.07，C5b-9（g/L）：575.46±197.26、659.26±160.77比501.40±141.51，均P〈0.05〕；随时间延长，NSTE-ACS组C3、C4无明显变化，C5b-9于3 d达高峰〔（700.63±218.42）g/L〕后下降；而STEMI组C3〔（1.37±0.33）g/L〕、C4〔（0.42±0.12）g/L〕、C5b-9〔（754.72±136.22）g/L〕均于3 d达高峰，且STEMI组发病3 d、7 d时补体C4、C5b-9水平均明显高于NSTE-ACS组。②与NSTE-ACS组比较，STEMI组肌钙蛋白T （TnT）、肌酸激酶同工酶（CK-MB）、可溶性细胞间黏附分子-1（sICAM-1）及全球急性冠状动脉事件注册（GRACE）评分、行经皮冠状动脉介入治疗（PCI）的比例明显升高，左室射血分数（LVEF）明显下降，而两组N末端B型脑钠肽前体（NT-proBNP）、纤维蛋白原（Fib）、再入院率和MACE发生率差异无统计学意义。③根据GRACE评分将ACS患者分为低危组（≤108分，26例）、中危组（109~140分，61例）、高危组（〉140分，83例）。中危组TnT、sICAM-1明显高于低危组；高危组TnT、sICAM-1、C3、C4、C5b-9明显高于中危组和低危组，LVEF明显低于中危组和低危组。④ Pearson相关分析显示，发病3 d时血清补体C3、C4、C5b-9与TnT（r值分别为0.481、0.367、0.292）、sICAM-1（r值分别为0.298、0.249、0.365）均呈正相关（均P〈0.01），与LVEF均呈负相关（r值分别为-0.384、-0.260、-0.200，均P〈0.01）；sICAM-1与TnT呈正相关（r=0.536，P=0.000），与LVEF呈负相关（r=-0.341，P=0.001）。结论ACS患者急性期存在补体激活，补体C3、C4、C5b-9参与了心肌损伤过程，可能是反映心肌损伤程度、预示心功能不良的指标。

ObjectiveTo study relationships between myocardial injury and the levels of serum complement C3, C4 and C5b-9 in patients with acute coronary syndrome （ACS）.MethodsA retrospectively analysis was conducted. 170 ACS patients [including 110 cases of ST-segment elevation myocardial infarction （STEMI） and 60 cases of non-ST-segment elevation acute coronary syndrome （NSTE-ACS）] with ischemic chest pain or chest discomfort onset within the prior 12 hours admitted to the cardiology department of Tianjin Union Medicine Center from January 2014 to July 2016 were enrolled. Thirty-six healthy cases were enrolled as control during the same time. The levels of serum complement C3, C4 and C5b-9 on 1, 3 and 7 days after admission and myocardial function indicators were analyzed. Major adverse cardiovascular events （MACE） and readmission rate were analyzed after 1 year follow-up. The correlation between serum complement levels and myocardial function indicators was analyzed by Pearson correlation analysis.Results① The levels of serum C3, C4 and C5b-9 on the first day in NSTE-ACS group and STEMI group were significantly higher than control group [C3 （g/L）： 1.04±0.33, 1.26±0.35 vs. 0.39±0.21, C4 （g/L）： 0.31±0.14, 0.33±0.10 vs. 0.19±0.07, C5b-9 （g/L）： 575.46±197.26, 659.26±160.77 vs. 501.40±141.51, all P 〈 0.05]. There were no changes of serum C3, C4 in NSTE-ACS group, but C5b-9 decreased after a peak （g/L： 700.63±218.42） at 3 days. Serum complements in STEMI group reached peak on the third day [C3 （g/L）： 1.37±0.33, C4 （g/L）： 0.42±0.12, C5b-9 （g/L）： 754.72±136.22]. The levels of serum C4 and C5b-9 in STEMI group were higher than NSTE-ACS group on the third and seventh day. ② The levels of troponin T （TnT）, creatine kinase-MB （CK-MB）, solution intercellular adhesion molecule-1 （sICAM-1）, global registry of acute coronary events （GRACE） scores and percutaneous coronary intervention （PCI） numbers in STEMI group were significantly higher than those in the NSTE-ACS group, which were as opposite as left ventricular ejection fraction （LVEF）. However, there were no significant differences in levels of serum N-terminal pro-brain nitric peptide （NT-proBNP）, Fibrinogen （Fib）, readmission rate and incidence of MACE between STEMI and NSTE-ACS groups. ③ According to GRACE, patients with ACS were divided into low risk group （≤ 108 scores, 26 cases）, intermediate risk group （109-140 scores, 61 cases） and highest group （〉 140 scores, 83 cases）. TnT and sICAM-1 in intermediate risk group were significantly increased as compared with low risk group. Levels of TnT, sICAM-1, C3, C4 and C5b-9 in the highest group were significantly higher than the low and intermediate risk groups, however the lowest LVEF was found in the highest group. ④ It was shown by Pearson correlation analyses that levels of serum C3, C4, C5b-9 were positively correlated with TnT （r value was 0.481, 0.367, 0.292, respectively, all P 〈 0.01）, sICAM-1 （r value was 0.298, 0.249, 0.365, respectively, all P 〈 0.01）, but negatively correlated with LVEF （r value was -0.384, -0.260, -0.200, respectively, all P 〈 0.01）. In addition sICAM-1 positively correlated with TnT （r = 0.536, P = 0.000）, but negatively correlated with LVEF （r = -0.341, P = 0.001）.ConclusionsSerum complements activation was found in the acute phase of ACS patients. Serum complement C3, C4 and C5b-9 are involved in the process of myocardial injury, and may reflect severity of myocardial injury and cardiac dysfunction.