| Objective: After experimental myocardial infarction(MI),circulating monocytes are activated and undergoing a rapid expansion.The proteolytic enzyme and reactive oxygen released by activated monocytes not only aggravate the injury of surviving myocardium after infarction,postpone the healing of infarct site,but also increase the instability of atherosclerotic plaque,which are main causes of adverse cardiovascular events in follow-up.Monocyte heterogeneity is widely acknowledged,and human monocytes can be classified into classical(CD14++CD16-,Mon1),intermediate(CD14++CD16+,Mon2),and nonclassical(CD14+CD16++,Mon3),which differ in the expression of CD14 and CD16.Moreover,the formation of monocyte-platelet aggregates(MPA),a sensitive marker for in vivo platelet activation,would further facilitate the adhension of monocyte to endothelial cells.Mon2 and Mon2 MPA are independent risk factors for MI and major adverse cardiovascular events(MACE).In the fundamental research,benefits of early angiotensin-converting enzyme inhibitors(ACEI)taking after MI can partially be attributed to its potent antiinflammatory impact on the splenic monocyte reservoir.MI liberats haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling.The progenitors then seeded the spleen,yielding a sustained boost in monocyte production.However,there is less evidence of whether ACEI and ?-blocker contribute to the dynamic changes of monocyte after STEMI,so the purpose of present study is to investigate the effects and clinical significance of ACEI and ?-blocker in dynamics of monocyte subsets and MAP of acute phase following STEMI.Methods: STEMI patients from December 2012 to May 2013(cohort 1)and January 2015 to December 2015(cohort 2)who admitted for emergency primary percutaneous coronary intervention(PCI)in the Heart Center of Pingjin Hospital were recruited.Without contraindications,STEMI patients were routinly treated with ACEI and ?-blocker within 24 hours.Peripheral blood of patients in cohort 1 was serially collected at time of admission,day2,3,5 and 7 after STEMI for flow cytometry(FCM)analysis of circulation monocyte subsets and MPA.Peripheral blood of patients in cohort 2 was collected at time of day2 after STEMI for FCM analysis.Then collected the information of drugs taking and recorded the MACE in 3 years.The area under curve(AUC)of dynamic change trajectory and the average of monocyte subsets and MAP were calculated.Results:(1)Cohort 1: A total of 96 STEMI patients admitted for PCI were recruited during a median follow-up of three years,29 cases of MACEs were recorded.Cohort 2: There were 121 STEMI patients recruited.Total cohort: Compared with patients without MACE,ones with MACE were older(P=0.021),more likely to have lower LVEF(P<0.001),higher Mon1,Mon2,Mon1 MPA and Mon2 MPA(all P<0.05),along with less taking of ACEI and ?-blocker(all P<0.05).(2)Cohort 1: Mon1 Avg?Mon1 MPA Avg?Mon2 Avg?Mon2 MPA Avg of EARLY ACEI(treated with ACEI within 24 hours)group was lower than NO ACEI group and LATE ACEI(treated with ACEI beyong 24 hours)group(all P<0.05).ALL monocyte subsets Avg and MPA Avg of EARLY ?-B(treated with ?-B within 24 hours)group were significantly lower than NO ?-B group and LATE ?-B(treated with ?-B beyong 24 hours)group(all P<0.05).(3)Cohort 1: Compared with patients of NO ACEI group,ones of EARLY ACEI group had lower Mon2 AUC [232.0(148.7,338.6)vs.392.6(247.9,588.0),P=0.013].Compared with patients of LATE ACEI group,ones of EARLY ACEI group had lower Mon2 AUC [232.0(148.7,338.6)vs.318.2(207.6,523.7),P=0.040].Every monocyte subset AUC and MPA AUC of EARLY ?-B group was significantly lower than NO ?-B group.Compared with patients of None group,every monocyte subset AUC and MPA AUC of ACEI AND ?-B group was significantly lower(all P<0.05).(4)Total cohort: Compared with patients of EARLY ACEI group,ones of LATE ACEI group and NO ACEI group had higher Mon2 count(P<0.05).Compared with patients of EARLY ?-B group,ones of LATE ?-B group and NO ?-B group had higher Mon2 count(P<0.05).Compared with patients of None group,Mon2 count of EARLY ACEI group,EARLY ?-B group and ACEI AND?-B group was significantly lower(all P<0.05).(5)ROC curve analysis: In cohort 1(AUC=0.647,95%CI: 0.521-0.773,P=0.024)and total cohort(AUC=0.734,95%CI: 0.655-0.814,P<0.001),Mon2 count on day2 had a clinical acceptable value for discrimination STEMI patients with and without MACE.(6)Cox regression analysis: Total cohort: Based on drug taking conditions,patients were divided into four groups: None,ACEI,?-B,ACEI AND ?-B.Compared with the ACEI AND ?-B group,the risk of MACE increased about 1 times(HR 1.974,95%CI: 1.201-3.315,0.039)in the patients of ?-B group,and the risk of MACE increased 0.6 times(HR 1.631,95%CI: 1.086-3.009,0.046)in the patients of ACEI group,and the risk of MACE increased 1.2 times(HR 2.174,95%CI: 1.014-4.794,0.045)in the patients of None group.Conclusion: Our study further certified that Mon2 is an independent risk factor for 3 years of MACE in patients with STEMI.Taking ?-blocker and/or ACEI at time of admission is able to decrease Mon2 of STEMI acute phase,and improve long-term survival.The sample of this study is small and the follow-up time is short,and subsequent studies need to be further validated in larger samples. |
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