ST段抬高型心肌梗死急性期单核细胞亚群与单核细胞—血小板聚集体的动态变化规律及临床意义
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摘要
研究目的：单核细胞亚群比例失衡和功能失调是众多炎症相关疾病发生发展重要病理生理学基础之一。人类单核细胞由三个亚群组成(经典型：CD14++CD16-单核细胞[Mon1]；中间型：CD14++CD16+单核细胞[Mon2]；非经典型：CD14+CD16++单核细胞[Mon3]),不同亚群具有不同的生理和病理生理学作用,其中具有促炎症表型的Mon2亚群的在心血管疾病病理生理学过程中发挥的作用备受关注。此外,单核细胞与血小板形成的聚集体(monocyte-platelet aggregate, MPA)是单核细胞活化和血小板聚集活性增强的结构基础,是与血栓和炎症相关疾病有关的新型标志物。近期有研究显示在ST段抬高型心肌梗死(ST segment elevation myocardial infarction, STEMI)患者中,Mon2单核细胞亚群的数量变化与心肌酶的升高呈正相关关系,提示心肌梗死后单核细胞亚群比例的变化,尤其是Mon2单核细胞的数量,可能是新的心肌梗死患者心脏功能和远期预后血液学标志物。因此本研究旨在国人STEMI患者中,明确以下两个尚未阐明的问题：1)STEMI后急性期(7天内)单核细胞亚群和MPA的动态变化规律；2)单核细胞亚群和MPA的变化与STEMI后心血管事件发生的关系。研究内容与方法：连续入选在中国人民武装警察部队后勤学院附属医院心脏中心接受急诊经皮冠状动脉介入治疗(percutaneous coronary intervention, PCI)的STEMI患者100例,其中男性78人,平均年龄58.20±11.00岁,女性22人,平均年龄64.11±9.10岁。分别在入院即刻(进行抗血小板药物治疗之前)、第2、3、5及7天共5个时间点抽取外周血进行单核细胞亚群和MPA的四色流式细胞术检测(CD14-FITC, CD16-PE, CD86-PE-Cy5和CD41-PE-Cy7)。入院24小时内及第7天完成心脏彩超检查。据患者基线资料和入院化验检查结果行GRACE评分、CRUSADE评分；依据造影结果进行SYNTAX评分。记录住院期间和出院1个月内出现的心血管死亡、致死性和非致死性缺血性脑卒中、再梗死、血运重建术、心力衰竭或心绞痛再入院等主要不良心脏事件(major adverse cardiovascular events, MACE)的发生情况。
结果：
1) MACE发生情况：全部入选的100名STEMI患者中,前壁心梗48例,下壁心梗52例；共发生7个MACE,其中院内事件4个,院外3个。院内1人发生缺血性脑卒中,3人死亡。死亡3人中1人只完成第1次流式细胞检测,1人完成2次流式细胞检测,第3人完成全部5次流式细胞检测。院外3个事件中,1人死亡,2人因心绞痛再次入院行靶血管血运重建术。
2)白细胞(white blood cell, WBC)、总单核细胞,总MPA计数动态变化：总体WBC计数在发病第1天即达到峰值,随后呈逐步下降趋势。总单核细胞计数逐渐升高,在第3天达峰值,随后呈下降趋势。总MPA和MPA占单核细胞的比例在心梗后第1天开始呈现逐渐下降的趋势,在第5天达到最低值。
3)Mon1和Mon1MPA动态变化：Monl计数第3天达峰值,第5天开始降低,Mon1占总单核细胞的百分比在第2天出现轻度降低,第3天再次升高达峰值,随后呈逐步降低趋势。Monl MPA呈现与总MPA一致的变化趋势,即STEMI后第一天处于峰值,随后缓慢下降,在第5天达到最低值。
4)Mon2和Mon2MPA动态变化：与第1天相比,Mon2计数第2天迅速升高[24.67cells/μL (14.96-45.73cells/μL) vs.48.78cells/μL (22.89-79.45cells/μL), P<0.0001(以中位数和四分位间距表示,下同)],并在第3天达峰值[74.13cells/μL (27.77-86.27cells/μL)],随后呈逐步降低趋势。Mon2百分比也是从第2天开始迅速升高[6.60%(4.38%-9.50%)vs.11.26%(7.56%-18.16%),.P<0.0001],并在第3天达峰值,随后呈逐步降低趋势。Mon2MPA的变化趋势与Mon2计数相似,也是从第2天明显增高并达峰值随后逐步降低。
5)Mon3和Mon3-MPA动态变化：Mon3计数在发病前3天呈逐步降低趋势,后逐步升高。Mon3百分比与计数呈一致性变化。Mon3MPA计数也是从发病开始至第3天呈逐步降低趋势,随后逐步增高。
6) LVEF与Mon2计数相关性分析：共有85例患者完成第7天经胸超声检测,Mon2计数的累积效应(以Mon2计数动态变化的曲线下面积[area under curve, AUC]表示)与第7天左心室射血分数(left ventricular ejection fraction, LVEF)呈负相关(r=-0.247,P=0.023,n=85)。前壁心梗组Mon2计数AUC值与LVEF呈负相关(r=-0.318,P=0.046,n=40),而下壁心梗组Mon2计数AUC值与LVEF无相关性(r=-0.092,P=N.S,n=45)。85例患者中Mon2计数峰值与第7天LVEF值呈负相关(r=-0.227,P=0.037,n=85)。前壁心梗组Mon2峰值计数与LVEF值呈负相关(r=-0.329,P=0.038,n=40),下壁心梗组Mon2峰值计数与LVEF值无相关性(r=-0.064,P=N.S,n=45)
7)Mon2计数和Mon2MPA计数相关性：第1天Mon2计数和Mon2MPA计数呈正相关(r=0.881,P<0.0001,n=100)；第3天Mon2计数和Mon2MPA计数呈正相关(r=0.841,P<0.0001,n=98)。
8) Logistic回归分析：以MACE事件的发生作为二分变量,经单变量、逐步回归多变量以及经传统心血管危险因素校正的多变量Logistic回归分析后显示,入院即刻的Mon2MPA计数是唯一与住院期间及出院后1个月MACE相关的独立危险因素(Mon2MPA每增加10cells/μL, OR=2.37[95%CI:1.265-4.44],0.007)。排除早期死亡病例,对98例完成全部流式细胞术分析的患者进行Logistic回归分析显示,STEMI后第3日Mon2计数是唯一与住院期间及出院后1个月MACE相关的独立危险因素(Mon2每增加10cells/μL, OR=1.248,[95%CI:1.029-1.513],P=0.024)受试者工作特征曲线(receiver operating characteristic curve, ROC curve)分析显示,STEMI后第3日Mon2计数对MACE事件发生的判别能力具有临床意义(AUC=0.823,[95%CI：0.679-0.964],P=0.016)。
9) Kaplan-Meier生存曲线分析：以第3日Mon2计数的中位数(43.4cells/μL)将98例患者分为两组,全部5例MACE均出现在Mon2计数>43.4cells/μL组(Log-rank检验P=0.0224)。
结论：本研究首次揭示了STEMI患者单核细胞亚群在急性期的动态变化规律,其中Mon2(CD14++CD16+)单核细胞在STEMI后第2天开始明显升高,第3天达峰值,随后缓慢下降。这一变化伴随着Mon2MPA的一致性改变。此外,本研究首次证实STEMI患者第3天Mon2数量和第1天Mon2MPA的数量是住院期间和出院后1个月MACE的独立预测因子。本研究首次将STEMI后单核细胞亚群的变化与心血管临床“硬终点”事件联系在一起,为STEMI患者危险分层提供了一个新的临床标志物。本研究的结论仍需要后续随访研究进一步证实。
Objective: Mounting evidence has shown that the imbalance of monocyte subset proportion and dysfunction is an important pathophysiological basis for many immune related diseases. Currently, human circulating monocytes are at least composed of three subsets with distinct physiological functions, including classical (CD14++CD16-,[Monl]), intermediate (CD14++CD16+,[Mon2]), and non-classical (CD14+CD16++,[Mon3]) monocytes. Among them, the "pro-inflammatory" Mon2subset has been received a great attention due to their active participation in cardiovascular pathophysiology. In addition, the formation of monocyte-platelet aggregates (MPA) is the structural basis for subsequent inflammatory and pro-thromboembolic activations. A recent study has confirmed a positive correlation between the Mon2monocyte subset quantity changes and elevated cardiac enzymes in patients with ST-segment elevation myocardial infarction (STEMI). These results indicate that changes in monocyte subsets after myocardial infarction, especially the increased number of Mon2monocytes, may be a novel marker for decompensated post-infarction heart failure and long-term prognosis. The present study was designed to investigate the following unresolved issues in a Chinese population suffered from STEMI:1) the dynamic profile of the monocyte subsets and their associations with MPAs in the acute phase (within7days) after STEMI;2) the prognostic values of monocyte subsets and MPAs for the occurrence of major cardiovascular events (MACE) after myocardial infarction.
Methods:A total of100consecutive STEMI patients admitted for emergency primary percutaneous coronary intervention (PCI) in the Heart Center of Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, were recruited in this study (78male, aged58.20±11.00;22female, aged64.11±9.10). Their venous blood was serially collected at time of admission, day2, day3, day5and day7after STEMI for flow cytometry (FCM) analysis of circulating monocyte subsets and MPAs using a four-color platform (CD14-FITC, CD16-PE, CD86-PE-Cy5and CD41-PE-Cy7). Transthoracic echocardiography was performed within24hours after symptom attack and on day7post infarction. According to laboratory test results on admission, the GRACE score, the CRUSADE score and the SYNTAX score based on coronary angiography were calculated. MACE, which was defined as cardiovascular death, fetal and non-fetal ischemic stroke, re-infarction, target vessel revascularization, and re-hospitalization due the heart failure and/or angina, were recorded in hospital and in one-month after discharge.
Results:
1) MACE occurrence:Among all100STEMI patients,48cases had left ventricular (LV) anterior wall infarction, and52cases with LV inferior wall infarction. A total of7MACE was recorded:4in hospital and3after discharge. Among the in-hospital MACE,1case suffered from non-fatal ischemic stroke, and another3cases died (one case finished only one FCM analysis, one case with two FCM tests, and one case finished all FCM tests). Among the3events occurred after discharge,1case died after discharge, and2cases underwent re-hospitalization for target vessel revascularization.
2) Dynamic changes of white blood cell (WBC) count, total monocyte and MPA count:The WBC count reached its plateau level when the first blood test was carried out on admission, and underwent a gradual decreasing trend thereafter. Total monocyte count gradually increased from the onset and reached the peak level on day3, and then presented with a decreasing trend. The total MPA count and MPA percent to total monocytes also underwent gradual decreasing trend from day1, and reached the nadir on day5.
3) Dynamic Changes of Monl and Monl MPA:Monl count was gradually increased from the onset and reached the peak on day3, then decreased till day5. Monl percent to total monocytes underwent a significantly decrease on day2, followed by an increasing trend, and reached the peak level on day3. Monl MPA count presented with a similar changing pattern with that of total MPA count.
4) Dynamic Changes of Mon2and Mon2MPA:Compared with day1, there was a rapid increase of the Mon2subset count [24.67cells/μL (14.96-45.73cells/μL) vs.48.78cells/μL (22.89-79.45cells/μL),P＜0.0001(shown as median with interquartile range)] as well as its percent to total monocytes [6.60%(4.38%-9.50%) vs.11.26%(7.56%-18.16%), P<0.0001] on day2after STEMI, peaking on day3[74.13cells/μL (27.77-86.27cells/μL)] followed by a gradual decrease, which was accompanied by a paralleled change in Mon2associated MPAs.
5) Dynamic Change of Mon3and Mon3MPA: Mon3count, Mon3percent to total monocytes, and Mon3MPA count were all gradually decreased from the onset to the first three days, followed by a gradual increase from day3. There was no obvious change in Mon3MPA percent during the investigation.
6) LVEF and Mon2count correlation analysis:Among the85patients who had undergone transthoracic echocardiography on day7, the accumulative effect of Mon2subset count (determined by area under curve [AUC] of Mon2count dynamics) was negatively correlated with LV ejection fraction (LVEF) on day7(Pearson r=-0.247,P=0.023, n=85). Specifically, the relationship between Mon2count AUC and LVEF was more obvious in patients suffered from anterior MI (Pearson r=-0.318,P=0.046, n=40), but not in patients with inferior wall MI (Pearson r=-0.092,P=N.S, n=45). In addition, the peak level of Mon2count and LVEF were negatively correlated (Pearson r=-0.227,P=0.037). Specifically, the relationship between peak Mon2count and LVEF was more obvious in patients suffered from anterior MI (Pearson r=-0.329,P=0.038, n=40), but not in patients with inferior wall MI (Pearson r=-0.064,P=NS, n=45).
7) The correlation between Mon2count and Mon2MPA count:The Mon2count and Mon2MPA count was positively correlated on day1(Pearson r=0.881, P<0.0001, n=100), and on day3(Pearson r=0.841,P<0.0001, n=98).
8) Logistic regression analysis:The risk factor adjusted multivariate stepwise Logistic regression analysis showed that day1Mon2MPA count was the only independent risk factor associated with in-hospital and one month MACE (for every10cells/μL increase, OR=2.37,[95%CI:1.265-4.44],P=0.007). After excluding2cases of early death who did not complete all flow cytometry analysis, Logistic regression analysis showed Mon2count on day3was the only independent risk factors for in-hospital and one month MACE (for every10cells/μL increase, OR=1.248,[95%CI:1.029-1.513],P=0.024). The receiver operating characteristic (ROC) curve analysis showed that Mon2count on day3 had a clinical acceptable value for discriminating STEMI patients with and without in-hospital and one month (AUC=0.823,[95%CI:0.679-0.964], P=0.016)
9) Using43.4cells/μL as the cutoff point value (median of Mon2count on day3, n=98), the Kaplan-Meier survival analysis showed that no MACE occurred in patients with Mon2count (day3)<43.4cells/μL (P=0.0224for Log-rank test).
Conclusions: The present study for the first time provides the detailed monocyte subset kinetics in acute phase after STEMI in humans. Specifically, a dramatic increase of the Mon2subset (CD14++CD16+) occurs on day2and peaks on day3, and then presents with a decreasing trend. The clinical significance of this dynamic profile is supported by the fact that Mon2count on day3and Mon2MPA count on day1, independently predict in-hospital and one month MACE in patients suffered from STEMI. This is the first study that linking monocyte subsets with "hard" clinical end points, and provides a new marker for risk stratification in patients with STEMI. Future long-term follow-up studies are required to validate our findings.
结果：
1) MACE发生情况：全部入选的100名STEMI患者中,前壁心梗48例,下壁心梗52例；共发生7个MACE,其中院内事件4个,院外3个。院内1人发生缺血性脑卒中,3人死亡。死亡3人中1人只完成第1次流式细胞检测,1人完成2次流式细胞检测,第3人完成全部5次流式细胞检测。院外3个事件中,1人死亡,2人因心绞痛再次入院行靶血管血运重建术。
2)白细胞(white blood cell, WBC)、总单核细胞,总MPA计数动态变化：总体WBC计数在发病第1天即达到峰值,随后呈逐步下降趋势。总单核细胞计数逐渐升高,在第3天达峰值,随后呈下降趋势。总MPA和MPA占单核细胞的比例在心梗后第1天开始呈现逐渐下降的趋势,在第5天达到最低值。
3)Mon1和Mon1MPA动态变化：Monl计数第3天达峰值,第5天开始降低,Mon1占总单核细胞的百分比在第2天出现轻度降低,第3天再次升高达峰值,随后呈逐步降低趋势。Monl MPA呈现与总MPA一致的变化趋势,即STEMI后第一天处于峰值,随后缓慢下降,在第5天达到最低值。
4)Mon2和Mon2MPA动态变化：与第1天相比,Mon2计数第2天迅速升高[24.67cells/μL (14.96-45.73cells/μL) vs.48.78cells/μL (22.89-79.45cells/μL), P<0.0001(以中位数和四分位间距表示,下同)],并在第3天达峰值[74.13cells/μL (27.77-86.27cells/μL)],随后呈逐步降低趋势。Mon2百分比也是从第2天开始迅速升高[6.60%(4.38%-9.50%)vs.11.26%(7.56%-18.16%),.P<0.0001],并在第3天达峰值,随后呈逐步降低趋势。Mon2MPA的变化趋势与Mon2计数相似,也是从第2天明显增高并达峰值随后逐步降低。
5)Mon3和Mon3-MPA动态变化：Mon3计数在发病前3天呈逐步降低趋势,后逐步升高。Mon3百分比与计数呈一致性变化。Mon3MPA计数也是从发病开始至第3天呈逐步降低趋势,随后逐步增高。
6) LVEF与Mon2计数相关性分析：共有85例患者完成第7天经胸超声检测,Mon2计数的累积效应(以Mon2计数动态变化的曲线下面积[area under curve, AUC]表示)与第7天左心室射血分数(left ventricular ejection fraction, LVEF)呈负相关(r=-0.247,P=0.023,n=85)。前壁心梗组Mon2计数AUC值与LVEF呈负相关(r=-0.318,P=0.046,n=40),而下壁心梗组Mon2计数AUC值与LVEF无相关性(r=-0.092,P=N.S,n=45)。85例患者中Mon2计数峰值与第7天LVEF值呈负相关(r=-0.227,P=0.037,n=85)。前壁心梗组Mon2峰值计数与LVEF值呈负相关(r=-0.329,P=0.038,n=40),下壁心梗组Mon2峰值计数与LVEF值无相关性(r=-0.064,P=N.S,n=45)
7)Mon2计数和Mon2MPA计数相关性：第1天Mon2计数和Mon2MPA计数呈正相关(r=0.881,P<0.0001,n=100)；第3天Mon2计数和Mon2MPA计数呈正相关(r=0.841,P<0.0001,n=98)。
8) Logistic回归分析：以MACE事件的发生作为二分变量,经单变量、逐步回归多变量以及经传统心血管危险因素校正的多变量Logistic回归分析后显示,入院即刻的Mon2MPA计数是唯一与住院期间及出院后1个月MACE相关的独立危险因素(Mon2MPA每增加10cells/μL, OR=2.37[95%CI:1.265-4.44],0.007)。排除早期死亡病例,对98例完成全部流式细胞术分析的患者进行Logistic回归分析显示,STEMI后第3日Mon2计数是唯一与住院期间及出院后1个月MACE相关的独立危险因素(Mon2每增加10cells/μL, OR=1.248,[95%CI:1.029-1.513],P=0.024)受试者工作特征曲线(receiver operating characteristic curve, ROC curve)分析显示,STEMI后第3日Mon2计数对MACE事件发生的判别能力具有临床意义(AUC=0.823,[95%CI：0.679-0.964],P=0.016)。
9) Kaplan-Meier生存曲线分析：以第3日Mon2计数的中位数(43.4cells/μL)将98例患者分为两组,全部5例MACE均出现在Mon2计数>43.4cells/μL组(Log-rank检验P=0.0224)。
结论：本研究首次揭示了STEMI患者单核细胞亚群在急性期的动态变化规律,其中Mon2(CD14++CD16+)单核细胞在STEMI后第2天开始明显升高,第3天达峰值,随后缓慢下降。这一变化伴随着Mon2MPA的一致性改变。此外,本研究首次证实STEMI患者第3天Mon2数量和第1天Mon2MPA的数量是住院期间和出院后1个月MACE的独立预测因子。本研究首次将STEMI后单核细胞亚群的变化与心血管临床“硬终点”事件联系在一起,为STEMI患者危险分层提供了一个新的临床标志物。本研究的结论仍需要后续随访研究进一步证实。
Objective: Mounting evidence has shown that the imbalance of monocyte subset proportion and dysfunction is an important pathophysiological basis for many immune related diseases. Currently, human circulating monocytes are at least composed of three subsets with distinct physiological functions, including classical (CD14++CD16-,[Monl]), intermediate (CD14++CD16+,[Mon2]), and non-classical (CD14+CD16++,[Mon3]) monocytes. Among them, the "pro-inflammatory" Mon2subset has been received a great attention due to their active participation in cardiovascular pathophysiology. In addition, the formation of monocyte-platelet aggregates (MPA) is the structural basis for subsequent inflammatory and pro-thromboembolic activations. A recent study has confirmed a positive correlation between the Mon2monocyte subset quantity changes and elevated cardiac enzymes in patients with ST-segment elevation myocardial infarction (STEMI). These results indicate that changes in monocyte subsets after myocardial infarction, especially the increased number of Mon2monocytes, may be a novel marker for decompensated post-infarction heart failure and long-term prognosis. The present study was designed to investigate the following unresolved issues in a Chinese population suffered from STEMI:1) the dynamic profile of the monocyte subsets and their associations with MPAs in the acute phase (within7days) after STEMI;2) the prognostic values of monocyte subsets and MPAs for the occurrence of major cardiovascular events (MACE) after myocardial infarction.
Methods:A total of100consecutive STEMI patients admitted for emergency primary percutaneous coronary intervention (PCI) in the Heart Center of Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, were recruited in this study (78male, aged58.20±11.00;22female, aged64.11±9.10). Their venous blood was serially collected at time of admission, day2, day3, day5and day7after STEMI for flow cytometry (FCM) analysis of circulating monocyte subsets and MPAs using a four-color platform (CD14-FITC, CD16-PE, CD86-PE-Cy5and CD41-PE-Cy7). Transthoracic echocardiography was performed within24hours after symptom attack and on day7post infarction. According to laboratory test results on admission, the GRACE score, the CRUSADE score and the SYNTAX score based on coronary angiography were calculated. MACE, which was defined as cardiovascular death, fetal and non-fetal ischemic stroke, re-infarction, target vessel revascularization, and re-hospitalization due the heart failure and/or angina, were recorded in hospital and in one-month after discharge.
Results:
1) MACE occurrence:Among all100STEMI patients,48cases had left ventricular (LV) anterior wall infarction, and52cases with LV inferior wall infarction. A total of7MACE was recorded:4in hospital and3after discharge. Among the in-hospital MACE,1case suffered from non-fatal ischemic stroke, and another3cases died (one case finished only one FCM analysis, one case with two FCM tests, and one case finished all FCM tests). Among the3events occurred after discharge,1case died after discharge, and2cases underwent re-hospitalization for target vessel revascularization.
2) Dynamic changes of white blood cell (WBC) count, total monocyte and MPA count:The WBC count reached its plateau level when the first blood test was carried out on admission, and underwent a gradual decreasing trend thereafter. Total monocyte count gradually increased from the onset and reached the peak level on day3, and then presented with a decreasing trend. The total MPA count and MPA percent to total monocytes also underwent gradual decreasing trend from day1, and reached the nadir on day5.
3) Dynamic Changes of Monl and Monl MPA:Monl count was gradually increased from the onset and reached the peak on day3, then decreased till day5. Monl percent to total monocytes underwent a significantly decrease on day2, followed by an increasing trend, and reached the peak level on day3. Monl MPA count presented with a similar changing pattern with that of total MPA count.
4) Dynamic Changes of Mon2and Mon2MPA:Compared with day1, there was a rapid increase of the Mon2subset count [24.67cells/μL (14.96-45.73cells/μL) vs.48.78cells/μL (22.89-79.45cells/μL),P＜0.0001(shown as median with interquartile range)] as well as its percent to total monocytes [6.60%(4.38%-9.50%) vs.11.26%(7.56%-18.16%), P<0.0001] on day2after STEMI, peaking on day3[74.13cells/μL (27.77-86.27cells/μL)] followed by a gradual decrease, which was accompanied by a paralleled change in Mon2associated MPAs.
5) Dynamic Change of Mon3and Mon3MPA: Mon3count, Mon3percent to total monocytes, and Mon3MPA count were all gradually decreased from the onset to the first three days, followed by a gradual increase from day3. There was no obvious change in Mon3MPA percent during the investigation.
6) LVEF and Mon2count correlation analysis:Among the85patients who had undergone transthoracic echocardiography on day7, the accumulative effect of Mon2subset count (determined by area under curve [AUC] of Mon2count dynamics) was negatively correlated with LV ejection fraction (LVEF) on day7(Pearson r=-0.247,P=0.023, n=85). Specifically, the relationship between Mon2count AUC and LVEF was more obvious in patients suffered from anterior MI (Pearson r=-0.318,P=0.046, n=40), but not in patients with inferior wall MI (Pearson r=-0.092,P=N.S, n=45). In addition, the peak level of Mon2count and LVEF were negatively correlated (Pearson r=-0.227,P=0.037). Specifically, the relationship between peak Mon2count and LVEF was more obvious in patients suffered from anterior MI (Pearson r=-0.329,P=0.038, n=40), but not in patients with inferior wall MI (Pearson r=-0.064,P=NS, n=45).
7) The correlation between Mon2count and Mon2MPA count:The Mon2count and Mon2MPA count was positively correlated on day1(Pearson r=0.881, P<0.0001, n=100), and on day3(Pearson r=0.841,P<0.0001, n=98).
8) Logistic regression analysis:The risk factor adjusted multivariate stepwise Logistic regression analysis showed that day1Mon2MPA count was the only independent risk factor associated with in-hospital and one month MACE (for every10cells/μL increase, OR=2.37,[95%CI:1.265-4.44],P=0.007). After excluding2cases of early death who did not complete all flow cytometry analysis, Logistic regression analysis showed Mon2count on day3was the only independent risk factors for in-hospital and one month MACE (for every10cells/μL increase, OR=1.248,[95%CI:1.029-1.513],P=0.024). The receiver operating characteristic (ROC) curve analysis showed that Mon2count on day3 had a clinical acceptable value for discriminating STEMI patients with and without in-hospital and one month (AUC=0.823,[95%CI:0.679-0.964], P=0.016)
9) Using43.4cells/μL as the cutoff point value (median of Mon2count on day3, n=98), the Kaplan-Meier survival analysis showed that no MACE occurred in patients with Mon2count (day3)<43.4cells/μL (P=0.0224for Log-rank test).
Conclusions: The present study for the first time provides the detailed monocyte subset kinetics in acute phase after STEMI in humans. Specifically, a dramatic increase of the Mon2subset (CD14++CD16+) occurs on day2and peaks on day3, and then presents with a decreasing trend. The clinical significance of this dynamic profile is supported by the fact that Mon2count on day3and Mon2MPA count on day1, independently predict in-hospital and one month MACE in patients suffered from STEMI. This is the first study that linking monocyte subsets with "hard" clinical end points, and provides a new marker for risk stratification in patients with STEMI. Future long-term follow-up studies are required to validate our findings.
引文
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