ST段抬高心肌梗死患者急性期循環(huán)單核細胞亞群改變與遠期預后：血管緊張素轉(zhuǎn)換酶抑制劑與β受體阻滯劑的影響
發(fā)布時間：2018-12-16 01:08
【摘要】：目的:心肌梗死(myocardial infarction,MI)后,循環(huán)單核細胞被迅速激活并釋放大量蛋白水解酶和活性氧,是引起后續(xù)主要不良心血管事件(major adverse cardiovascular events,MACE)的原因之一。根據(jù)單核細胞表面CD標志物的表達差異,人單核細胞分為三個亞群:經(jīng)典型(CD14++CD16-,Mon1)、中間型(CD14++CD16+,Mon2)和非經(jīng)典型(CD14+CD16++,Mon3)。此外,血小板被活化后與單核細胞結(jié)合形成單核細胞血小板聚集體(monocyte-platelet aggregates,MPA),參與多種病理生理過程。研究證實,Mon2及Mon2 MPA是MI患者發(fā)生MACE的獨立危險因素�；A研究證實,血管緊張素轉(zhuǎn)換酶抑制劑(angiotensin-converting enzyme inhibitor,ACEI)可以抑制MI小鼠單核細胞從骨髓和脾臟的動員,進而可改善MI誘發(fā)的單核細胞增多,因此有助于解釋ACEI的臨床收益。MI后,激活的交感-腎上腺素軸在單核細胞的骨髓動員中發(fā)揮作用,提示β受體阻滯劑可能降低梗死區(qū)域的循環(huán)單核細胞數(shù)量。然而,目前尚缺乏ACEI和β受體阻滯劑對ST段抬高心肌梗死(ST-segment elevation myocardial infarction,STEMI)后單核細胞動態(tài)變化影響的證據(jù),因此本研究旨在探討STEMI患者急性期ACEI及β受體阻滯劑的臨床應用對循環(huán)單核細胞數(shù)量和遠期預后的影響。方法:入選2012年12月至2013年5月(隊列1)及2015年1月至2015年12月(隊列2)發(fā)病后24小時內(nèi)就診于武警后勤學院附屬醫(yī)院(平津醫(yī)院)心臟中心接受急診經(jīng)皮冠狀動脈介入治療(percutaneous coronary intervention,PCI)并行外周血單核細胞亞群流式分析的STEMI患者。STEMI患者發(fā)病24小時內(nèi),在無禁忌的情況下,均常規(guī)口服應用ACEI及β受體阻滯劑。隊列1患者分R%于入院即刻、第2、3、5及7天抽取外周血進行單核細胞亞群流式分析。隊列2患者于入院第2天抽取外周血進行單核細胞亞群流式分析。隨訪患者3年內(nèi)MACE的發(fā)生情況。計算隊列1中每位STEMI患者單核細胞亞群軌跡的曲線下面積(Area Under Curve,AUC)和單核細胞計數(shù)的均數(shù)(average,Avg)作為各單核細胞亞群在整個急性期變化趨勢的評價指標。結(jié)果:(1)隊列1中收錄了STEMI患者共96例。隊列2中收錄121例�？傃芯筷犃兄�:本研究最終納入217例STEMI患者。3年的隨訪中共46例患者發(fā)生MACE,其中心源性死亡10例、非致死性缺血性卒中3例、再發(fā)MI 3例、心力衰竭15例、需再次行急診或擇期血運重建15例。(2)隊列1:入院24小時內(nèi)應用ACEI患者的Mon1 Avg、Mon1 MPA Avg、Mon2 Avg、Mon2 MPA Avg水平均低于入院期間未應用ACEI及入院24小時后應用ACEI患者(all P0.05)。入院24小時內(nèi)應用β受體阻滯劑患者急性期各單核細胞亞群均數(shù)及亞群相關MPA均數(shù)顯著低于入院期間未用β受體阻滯劑及入院24小時后應用β受體阻滯劑患者(all P0.05)。(3)隊列1:與住院期間未應用ACEI及入院24小時后應用ACEI患者相比,入院24小時內(nèi)應用ACEI患者Mon2 AUC更低(all P0.05)。與住院期間未應用β受體阻滯劑患者相比,入院24小時內(nèi)應用β受體阻滯劑患者急性期的各單核細胞亞群AUC及亞群相關MPA AUC水平更低(all P0.05)。(4)總研究隊列:與入院24小時內(nèi)應用ACEI患者相比,住院期間未應用ACEI及入院24小時后應用ACEI患者的Mon2計數(shù)水平均更高(all P0.05)。與入院24小時內(nèi)應用β受體阻滯劑患者相比,住院期間未應用β受體阻滯劑及入院24小時后應用β受體阻滯劑患者的Mon2計數(shù)值均更高(all P0.05)。(5)ROC曲線分析:隊列1中及總研究隊列中,Mon2計數(shù)的AUC分別是0.647(95%CI:0.521-0.773,P=0.024)及0.734(95%CI:0.655-0.814,P0.001),Mon2計數(shù)對MACE事件發(fā)生的判別能力均具有臨床意義,提示Mon2計數(shù)是判別STEMI患者是否發(fā)生3年MACE較好的預測因子。(6)COX回歸分析:總研究隊列中,根據(jù)住院期間用藥情況將STEMI患者分為四組,并用性別、BMI、門球時間、吸煙史、高血壓史和糖尿病史等傳統(tǒng)心血管疾病危險因素進行校正,與ACEI ANDβ-B組相比,None組患者發(fā)生MACE的風險增加了約1.2倍(HR 2.174,95%CI:1.014-4.794,0.045)。結(jié)論:本研究進一步證實,Mon2是影響STEMI患者3年MACE的獨立危險因素;STEMI急性期患者早期應用ACIE及β受體阻滯劑可明顯降低循環(huán)Mon2水平,并減少MACE的發(fā)生,改善預后。
[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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R542.22
本文編號：2381599
[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.
【學位授予單位】：天津醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R542.22
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