ST段抬高心肌梗死患者急性期循环单核细胞亚群改变与远期预后：血管紧张素转换酶抑制剂与β受体阻滞剂的影响

发布时间：2018-12-16 01:08

【摘要】：目的:心肌梗死(myocardial infarction,MI)后,循环单核细胞被迅速激活并释放大量蛋白水解酶和活性氧,是引起后续主要不良心血管事件(major adverse cardiovascular events,MACE)的原因之一。根据单核细胞表面CD标志物的表达差异,人单核细胞分为三个亚群:经典型(CD14++CD16-,Mon1)、中间型(CD14++CD16+,Mon2)和非经典型(CD14+CD16++,Mon3)。此外,血小板被活化后与单核细胞结合形成单核细胞血小板聚集体(monocyte-platelet aggregates,MPA),参与多种病理生理过程。研究证实,Mon2及Mon2 MPA是MI患者发生MACE的独立危险因素。基础研究证实,血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitor,ACEI)可以抑制MI小鼠单核细胞从骨髓和脾脏的动员,进而可改善MI诱发的单核细胞增多,因此有助于解释ACEI的临床收益。MI后,激活的交感-肾上腺素轴在单核细胞的骨髓动员中发挥作用,提示β受体阻滞剂可能降低梗死区域的循环单核细胞数量。然而,目前尚缺乏ACEI和β受体阻滞剂对ST段抬高心肌梗死(ST-segment elevation myocardial infarction,STEMI)后单核细胞动态变化影响的证据,因此本研究旨在探讨STEMI患者急性期ACEI及β受体阻滞剂的临床应用对循环单核细胞数量和远期预后的影响。方法:入选2012年12月至2013年5月(队列1)及2015年1月至2015年12月(队列2)发病后24小时内就诊于武警后勤学院附属医院(平津医院)心脏中心接受急诊经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)并行外周血单核细胞亚群流式分析的STEMI患者。STEMI患者发病24小时内,在无禁忌的情况下,均常规口服应用ACEI及β受体阻滞剂。队列1患者分R%于入院即刻、第2、3、5及7天抽取外周血进行单核细胞亚群流式分析。队列2患者于入院第2天抽取外周血进行单核细胞亚群流式分析。随访患者3年内MACE的发生情况。计算队列1中每位STEMI患者单核细胞亚群轨迹的曲线下面积(Area Under Curve,AUC)和单核细胞计数的均数(average,Avg)作为各单核细胞亚群在整个急性期变化趋势的评价指标。结果:(1)队列1中收录了STEMI患者共96例。队列2中收录121例。总研究队列中:本研究最终纳入217例STEMI患者。3年的随访中共46例患者发生MACE,其中心源性死亡10例、非致死性缺血性卒中3例、再发MI 3例、心力衰竭15例、需再次行急诊或择期血运重建15例。(2)队列1:入院24小时内应用ACEI患者的Mon1 Avg、Mon1 MPA Avg、Mon2 Avg、Mon2 MPA Avg水平均低于入院期间未应用ACEI及入院24小时后应用ACEI患者(all P0.05)。入院24小时内应用β受体阻滞剂患者急性期各单核细胞亚群均数及亚群相关MPA均数显著低于入院期间未用β受体阻滞剂及入院24小时后应用β受体阻滞剂患者(all P0.05)。(3)队列1:与住院期间未应用ACEI及入院24小时后应用ACEI患者相比,入院24小时内应用ACEI患者Mon2 AUC更低(all P0.05)。与住院期间未应用β受体阻滞剂患者相比,入院24小时内应用β受体阻滞剂患者急性期的各单核细胞亚群AUC及亚群相关MPA AUC水平更低(all P0.05)。(4)总研究队列:与入院24小时内应用ACEI患者相比,住院期间未应用ACEI及入院24小时后应用ACEI患者的Mon2计数水平均更高(all P0.05)。与入院24小时内应用β受体阻滞剂患者相比,住院期间未应用β受体阻滞剂及入院24小时后应用β受体阻滞剂患者的Mon2计数值均更高(all P0.05)。(5)ROC曲线分析:队列1中及总研究队列中,Mon2计数的AUC分别是0.647(95%CI:0.521-0.773,P=0.024)及0.734(95%CI:0.655-0.814,P0.001),Mon2计数对MACE事件发生的判别能力均具有临床意义,提示Mon2计数是判别STEMI患者是否发生3年MACE较好的预测因子。(6)COX回归分析:总研究队列中,根据住院期间用药情况将STEMI患者分为四组,并用性别、BMI、门球时间、吸烟史、高血压史和糖尿病史等传统心血管疾病危险因素进行校正,与ACEI ANDβ-B组相比,None组患者发生MACE的风险增加了约1.2倍(HR 2.174,95%CI:1.014-4.794,0.045)。结论:本研究进一步证实,Mon2是影响STEMI患者3年MACE的独立危险因素;STEMI急性期患者早期应用ACIE及β受体阻滞剂可明显降低循环Mon2水平,并减少MACE的发生,改善预后。
[Abstract]:Objective: After myocardial infarction (MI), circulating mononuclear cells are rapidly activated and release a large amount of proteolytic enzyme and active oxygen, which is one of the causes of follow-up major adverse cardiovascular events (MACE). On the basis of the difference in the expression of CD markers on the surface of monocytes, human monocytes were divided into three subpopulations: typical (CD14 + + CD16-, Mon1), intermediate (CD14 + + CD16 +, Mon2), and non-typical (CD14 + CD16 + +, Mon3). In addition, the platelet is activated to form a monocyte-platelet aggregate (MPA) in combination with the monocytes to participate in a variety of pathophysiological processes. The study confirmed that Mon2 and Mon2 MPA were independent risk factors for MACE in MI patients. The basic study confirmed that the angiotensin-converting enzyme inhibitor (ACEI) can inhibit the mobilization of the mononuclear cells of the MI mice from the bone marrow and the spleen, and further improve the number of mononuclear cells induced by the MI, thus contributing to the interpretation of the clinical benefit of the ACEI. After MI, the activated sympathetic-epinephrine axis plays a role in the bone marrow mobilization of the monocytes, suggesting that the androgen receptor blocker may reduce the number of circulating monocytes in the infarct zone. However, there is a lack of evidence of the effects of ACEI and platelet receptor blockers on the dynamic changes of monocytes after ST-segment elevation myocardial infarction (STEMI), The purpose of this study is to study the effect of the clinical application of ACEI and VEGF in the acute phase of STEMI on the number of circulating monocytes and long-term prognosis. Methods: From December 2012 to May 2013 (Cohort 1) and from January 2015 to December 2015 (Cohort 2), the heart center of the Affiliated Hospital of the Military Police Logistics Academy (Pingjin Hospital) received emergency percutaneous coronary intervention. PCI) patients with STEMI in parallel peripheral blood monocyte subpopulation flow analysis. In the 24-hour period of onset of STEMI, ACEI and androgen receptor blockers were routinely administered orally in the absence of taboos. Peripheral blood was extracted from peripheral blood for subpopulation flow analysis at 2, 3, 5 and 7 days in Cohort 1. The patients with Cohort 2 were subjected to subpopulation-flow analysis of the peripheral blood on the second day of admission. The occurrence of MACE within 3 years of follow-up. The mean (average, Avg) of the subpopulation trajectory of the monocyte subpopulation in each STEMI patient in Cohort 1 was calculated as an evaluation index for each of the monocyte subpopulations in the entire acute phase. Results: (1) There were 96 patients with STEMI in Cohort 1. 121 cases were included in Cohort 2. In the total study cohort, 217 patients with STEMI were included in this study. In the 3-year follow-up, there were 46 patients with MACE, including 10 cases of cardiac death, 3 non-fatal ischemic stroke, 3 cases of MI, 15 cases of heart failure, and 15 cases of emergency or elective revascularisation. (2) Cohort 1: The level of Mon1 Avg, Mon1 MPA Avg, Mon2Ag, and Mon2 MPA Avg in patients with ACEI within 24 hours of admission was lower than that of ACEI and ACEI after 24 hours of admission (all P0.05). The mean number of sub-group and subgroup-related MPA in the acute stage of the patients who were admitted for 24 hours of admission was significantly lower than that of the patients who did not use the androgen receptor blocker and after 24 hours of admission (all P0.05). (3) Cohort 1: Compared with the patients who did not use ACEI during the hospitalization and after 24 hours of admission, the AUC of the Mon2 AUC was lower in the patients admitted to the hospital for 24 hours (all P0.05). The AUC and subgroup-related MPA AUC levels were lower in the acute phase of the patients admitted to the hospital for 24 hours compared to those who did not apply the androgen receptor blocker (all P0.05). (4) The total study cohort: compared with the patients who received ACEI within 24 hours of admission, the level of Mon2 in the patients who had not applied ACEI and ACEI after 24 hours of admission was higher (all P0.05). The number of Mon2 in the patients who did not use the antigen-receptor blocker during the hospitalization and after 24 hours of admission was higher (all P0.05) compared to the patients who were admitted to the hospital for 24 hours. (5) ROC curve analysis: in Cohort 1 and in the total study cohort, the AUC of the Mon2 counts was 0.647 (95% CI: 0.521-0.773, P = 0.024) and 0.734 (95% CI: 0.655-0.814, P0.001), and the ability of the Mon2 to count on the MACE event was clinically significant. It is suggested that the Mon2 count is a good predictor of whether the patients with STEMI have a 3-year MACE. (6) COX regression analysis: in the total study cohort, the STEMI patients were divided into four groups according to the medication during the hospitalization, and the risk factors of the traditional cardiovascular diseases such as sex, BMI, door ball time, smoking history, history of hypertension and the history of diabetes were corrected, compared with the ACEI AND A-B group, The risk of MACE in the None group increased by about 1. 2-fold (HR 2.174, 95% CI: 1,014-4.794, 0.045). Conclusion: The study further confirmed that Mon2 is an independent risk factor for the 3-year MACE in patients with STEMI. In the early stage of STEMI, the early application of ACIE and platelet receptor blockers can significantly reduce the level of circulating Mon2 and reduce the occurrence of MACE and improve the prognosis.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.22

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