| BackgroundIn recent years,with the development of social economy and the change of people's lifestyle,the incidence of coronary heart disease(CHD)has been increased year by year and increasingly younger,seriously threating human health.Acute coronary syndrome(ACS)is an important type of life-threatening coronary heart disease.Percutaneous coronary intervention(PCI)is an important method to treatment of CHD.PCI can effectively alleviate coronary artery stenosis,open occlusive coronary artery and reperfusion of ischemic myocardium in patients with acute coronary syndrome,significantly improve cardiac function and reduce disability and mortality in patients with ACS.At present,the number of PCI patients with ACS is increasing,and patients benefit significantly.However,reperfusion injury often occurs after PCI,resulting in slow or no reflow of coronary arteries,which endangers patients' lives.Clinically,the levels of myocardial ischemia-reperfusion injury(IRI)can be reflected by detecting the levels of myocardial injury markers,vascular endothelial injury markers and inflammatory markers.Therefore,how to reduce myocardial IRI and prevent slow blood flow or no-reflow in PCI treatment of ACS patients is an urgent problem for clinicians.Remote ischemic preconditioning(RIPC)is derived from ischemic preconditioning(IPC).In recent years,it has been found to have the same effect of alleviating myocardial IRI.Compared with IPC,it is easy to operate,less invasive,and clinically feasible.Although,some animal experiments have proved that IPC can alleviate the vascular endothelial function injury and inflammatory response caused by IRI in mice.Regrettably,RIPC is currently only used in PCI treatment studies of some patients with CHD.Some clinical studies showed that RIPC can reduced the release of myocardial injury markers and inflammatory factors,while some studies have showed that RIPC failed alleviate myocardial IRI after PCI.Now there are relatively few clinical studies on RIPC in ACS patients.No relevant clinical studies have found whether RIPC has an effective effect on both myocardial reperfusion injury and inflammatory response after PCI in ACS patients.The safety and efficacy clinical application RIPC has yet to be evaluated.ObjectiveTo explore the effects of RIPC on myocardial injury and endothelial function damage and vascular inflammation with detecting and analyzing the levels of CK-MB,cTnI,vWF,sICAM-1,sVCAM-l,hs-CRP,MPO and SOD in patients with ACS after PCI.Patients were followed up and recorded the incidence of major adverse cardiac events(MACE)at 6 months after PCI.To provide theoretical guidance for RIPC in patients with ACS before PCI and lay the foundation for further study of RIPC in cardiac protection mechanism.Methods336 patients with ACS who underwent PCI in the Department of Cardiology,Taian Central Hospital from October 2015 to December 2017 were enrolled.All patients were randomized assigned to control group(N=172)and RIPC group(N=164).The patients of RIPC group were given five times of five minutes ischemia(pressure maintained at 200mmHg)and five minutes reperfusion around the upper arm at 2h before surgery with the RIPC instrument.Control group did not receive RIPC.The levels of serum CK-MB,CK-MB,cTnI,sICAM-1,sVCAM-1,vWF,hs-CRP,MPO and SOD were measured in both groups at 6 am in the day of PCI,and 12 hours and 24 hours after PCI.The major adverse cardiac events including readmission,myocardial infarction,heart failure and death due to coronary heart disease were recorded at 6 months after PCI.All data in the study were analyzed and processed using SPSS20.0 statistical software.The measurement data were tested for normal distribution and homogeneity of variance.Normally distributed mesurement data are expressed as average plus or minus standard deviation.Skew distributed data are represented by the median(quartile).T test was used for continuous variables that conform to normal distribution and homogeneity of variance.Correct T test was adopted for the data with different variances obtained by Levene's Test for Equality of Variances.Counting data was expressed as percentages,and chi-square test or Fisher exact probability method was used to compare the rates or constituent ratios between groups.The levels of myocardial damage markers(CK-MB,cTnI),endothelial function indicators(vWF,sICAM-1,sVCAM-1)and serum inflammatory markers(hs-CRP,MPO,SOD)before and after pretreatmen between the groups were compared by the repeated measure of ANOVA.Lsd-t test was used for pairwise comparison between groups at different time points,and pairwise comparison between groups at different time points was conducted with paired t test.P<0.05 was considered to be statistically significant.Results1.RIPC group and the control group compared at baseline,there was no significant difference in general condition,such as age,sex,smoking,history of diabetes,hypertension,related laboratory examination and clinical drug use(P>0.05).2.There was no significant difference between the two groups in lesion vessel location,ACC/AHA classification,balloon dilatation,number of stents implanted,TIMI blood flow after operation,stent shedding or improper position,dosage of contrast medium and application of postoperative antithrombotic anticoagulant drugs(P>0.05).3.The baseline biomarkers including CK-MB?cTnI?vWF?sICAM-1?sVCAM-1?hs-CRP?MPO?SOD did not differ between RIPC group and control group before PCI(P>0.05).Biomarkers including CK-MB,cTnI,vWF,sICAM-1,sVCAM-1,Hs-CRP and MPO were significantly higher at 12 and 24 hours after PCI than those before PCI(P<0.05),but SOD was significantly lower at 12 and 24 hours after PCI(P<0.05).There was a significant difference in main factors between groups(P<0.001).The levels of markers(CK-MB,cTnI,vWF,sICAM-1,sVCAM-1,Hs-CRP,MPO)in RIPC group were all or partially lower than those in control group at 12 or 24 hours after PCI,whereas the levels of SOD in RIPC group were significantly higher than those in control group at 12 or 24 hours after PCI(P<0.001).4.Comparison of the proportion of patients with different levels of cTnI after PCI between the two groups:The proportion of patients with no more than ULN in RIPC group was significantly higher than that in the control group(P<0.05);The proportion of patients with ULN<cTnl<5 times of ULN and cTnI>5 times of ULN in RIPC group was not significantly different from that in the control group(P>0.05).5,No significant adverse reactions were observed during hospitalization and 6 months after PCI in patients accepting ischemic preconditioning.Compared with the control group,there was no significant difference in the incidence of MACE within 6 months after PCI in RIPC group.(P>0.05).Conclusions1.The application of RIPC before PCI is safe and effective in ACS patients.2.RIPC can alleviate the myocardial reperfusion injury,vascular endothelial injury and inflammatory response in patients with ACS after PCI,and improve coronary artery no-reflow and myocardial microcirculation.3.The cardioprotective mechanism of RIPC in patients with ACS after PCI may be related to decreasing the levels of CK-MB,cTnI,vWF,sICAM-1,sVCAM-1,MPO,hs-CRP and increasing the level of SOD after PCI through endogenous pathway,which provides a theoretical guidance for the application of RIPC in patients with ACS before PCI.4.RIPC did not show a reduction of MACE in ACS patients within 6 months after PCI.BackgroundPercutaneous coronary interention(PCI)has become the main treatment of coronary heart disease,especially in patients with ACS.With the extensive development of PCI,the use of contrast media in PCI is increasing,and the incidence of contrast-induced nephropathy(CIN)is also increasing,which is a common complication of interventional therapy for coronary heart disease.According to the definition of European Society of Urogenital Radiology.CIN refers that serum creatinine(Scr)level is increased by>25%or 0.5mg/dL(44umol/L)compared with the original basis after intravascular injection of contrast medium for 48-72h excluding other factors affecting renal function.CIN can prolong patient hospitalization time and increase the risk of dialysis and death.In addition to hydration treatment outside,CIN no specific effective treatment options,there is an urgent need to find new ways to reduce the incidence of CIN.At present,most studies have confirmed that the main mechanism of CIN originates from renal ischemia and reperfusion injury.Therefore,prevention of renal ischemia and hypoxia injury may be an effective measure to prevent CIN.Remote ischemic preconditioning(RIPC)is an effective endogenous protective mechanism against ischemic reperfusion injury.It is not only protects the heart,but also protects other organs such as the kidney and brain.Animal experiments have showed that RIPC can alleviate the reperfusion injury of ischemic myocardium.Studies on the prevention of CIN is still in the preliminary stage.However,the preventive effect of RIPC on CIN in the perioperative period of ACS patients has not been reported.ObjectiveThis study included patients with ACS who underwent elective coronary angiography(CAG)or percutaneous coronary intervention(PCI)to detect serum creatinine(Scr),glomerular filtration rate(eGFR),and cystatin C(CysC),?2 microglobulin ?2-MG)and neutrophil gelatinase-associated lipocalin(NGAL)before and after operation.The main adverse renal events and major adverse cardiovascular events(MACE)were recorded at 6 months tafter operation.The preventive effect of RIPC on CIN after interventional therapy and he prognosis of patients were evaluated.To explore the risk factors and protective factors of CIN,and provide a theoretical basis for the clinical application of RIPC in preventing CIN.Methods408 patients with ACS who were hospitalized for CAG or PCI treatment in the department of cardiology of Tai'an City Central Hospital from October 2015 to December 2017 were enrolled and randomized assign 208 to the control group and 200 to the RIPC group.The patients of RIPC group were given five times of 5-minute ischemia(pressure maintained at 200mmHg)and 5-minute reperfusion around the upper arm at 2h before surgery with the RIPC instrument.Control group did not receive RIPC.The general clinical data of the two groups were collected,and the clinical medication status,intraoperative contrast medium dosage and the characteristics of diseased vessels of the two groups were recorded.All patients received standard hydration therapy before CAG or PCI(intravenous infusion of 0.9%sodium chloride l.Oml/kg/h from 12 hours before surgery to 12 hours after surgery).The level of Scr,eGFR,Cys C,?2-MG,NGAL were measured in all patients at 6 am befor the day of CAG,and 4hNGAL,24h NGAL,24h and 72h Scr,eGFR,Cys C,?2-MG after surgery.The incidence of CIN was compared between the two groups..Six months follow-up was completed and the incidence of major adverse cardiac and renal events(dialysis or renal replacement therapy after contrast media use)was analyzed.The patients were divided 48 to CIN group and 360 to non-CIN group according to the occurrence of CIN.The general condition of the two groups was compared and the changes of renal function before and after CAG or PCI in CIN group were observed.Univariate and multivariate logistic regression analysis of risk factors for CIN were performed in the two groups to explore the risk factors of CIN.Results1.The baseline demographic characteristics,including age,sex,rate of smoking,combined disease and past medical history,preoperative assistant examination results,clinical drug use,features of coronary angiographic lesions,dosage of contrast medium,number of stents implantation and postoperative use of antithrombotic drugs,were similar in both groups(P>0.05).2.There were 48 patients with CIN in the RIPC group and the control group,including 13 patients in the RIPC group and 35 patients in the control group.The incidence of CIN in the RIPC group was significantly lower than that in the control group,with statistically significant differences(x2= 0.475,P=0.001).In patients who only undergoing CAG,CIN incidence in RIPC group was significantly lower than that in control group,and the difference was statistically significant(x2=6.746,P=0.009).In patients undergoing PCI,CIN incidence in RIPC group was significantly lower than that in control group(x2=4.749,P=0.029).In the control group,CIN incidence in PCI patients was significantly higher than that in CAG patients(x2=5.215,P=0.022).In the RIPC group,CIN incidence in PCI patients was significantly higher than that in CAG patients(x2=4.763,P=0.029).3.Comparison of renal injury indexes between two groupsAccording to ANOVA of repeated measurement of two factors,the differences of renal function indicators including Scr,eGFR,CysC,?2-MG and NGAL levels between the two groups were statistically significant(Fgroup= 26.628,P<0.001;Fgroup-5.368,P=0.021;Fgroup=152.198,P<0.001;Fgroup= 27.663,P<0.001;Fgroup=13.014,P<0.001).The differences of all indicators' levels in different time were statistically significant(Ftime=44.638,P<0.001;Ftime=30.462,P<0.001;Ftime=313.557,P<0.001;Ftime=12.307,P<0.001;Ftime=53.778,P<0.001).The variation trend of Scr,CysC,?2-MG and NGAL levels over time varied with different groups(Fgroup×time=13.299,P<0.001;Fgroup×time=88.580,P<0.001;Fgroup×time=8.266,P<0.001;Fgroup×time=9.320,P<0.001).Comparison of the differences in different time in each group showed that the levels of Scr,CysC,and ?2-MG at 24h after surgery were all higher than the preoperative level(P<0.05),and the level of eGFR at 24h after surgery was lower than the preoperative level(P<0.05);and the levels of CysC,and eGFR were no statistically significant difference at 72h after surgery(P>0.05),but the levels of Scr and ?2-MG at 72h after surgery was higher than the preoperative level(P<0.05).The 4h postoperative level of NAGL in both the control group and the treatment group was lower than that before surgery(P<0.05),while the 24h postoperative level was not statistically significant(P>0.05).Comparison of the differences between the two groups at the same time point showed that no statistical significance between the two groups before the operation(P>0.05);Scr and CysC levels in the RIPC group were significantly lower than those in the control group(P<0.05)24 h after surgery,and the level of eGFR at 24h after surgery was higher than the control group(P<0.05);the level of Scr and ?2-MG at 72h after surgery in the RIPC group was lower than that in the control group(P<0.001);the level of NGAL at 4h after surgery in RIPC treatment group was lower than that of control group(P<0.05).4.History of diabetes,high blood pressure,level of hemoglobin,CysC,Scr,eGFR at admission,LV,LVEF,dosage of contrast medium,treatment with CAG and PCI and RIPC processing was statistically significant different between CIN and non-CIN group(P<0.05),while other general conditions such as age,sex,body mass index,hyperlipidemia did not differ between the two groups(P>0.05).5.Univariate and multivariate logistic regression analysis were used to explore the risk factors and protective factors of CIN.Include age,sex,body mass index,history of hyperlipidemia,diabetes history,history of high blood pressure,hemoglobin,preoperative CysC,preoperative Scr,eGFR,left ventricular size(LV),left ventricular ejection fraction,dosage of contrast medium,CAG,PCI and the preconditioning of RIPC processing into the logistic regression analysis model.Univariate analysis results showed that diabetes mellitus(OR=2.061,95%CI 1.101?3.857,P=0.024),hypertension(OR=1.968,95%CI 1.033-3.750,P=0.039),hemoglobin(OR=1.022,95%CI 1.000-1.045,P=0.045),preoperative CysC(OR=15.569,95%CI 7.665?30.873,P<0.001),preoperative Scr(OR=1.060,95%CI 1.040?1.081,P<0.001),preoperative eGFR(OR=0.95,95%CI 0.937?0.972,P<0.001),LV(OR=1.067,95%CI 1.015?1.121,P=0.011),LVEF(OR=1.082,95%CI 1.019?1.148,P=0.010),contrast medium dosage(OR=1.012,95%CI 1.006?1.018,P<0.001),CAG(OR=0.393,95%CI 0.212?0.728,P=0.003),PCI(OR=2.544,95%CI 1.373-4.713,P=0,003)are risk factors for promoting CIN occurrence after surgery,while preoperative RIPC treatment(OR=0.344,95%CI 0.176?0.671,P=0.002)are protective factors for reducing CIN risk after surgery.Multiple regression analysis showed that diabetes mellitus(OR=1.978,95%CI 1.176-4.215,P=0.031),preoperative CysC(OR=11.490,95%CI 9.079?22.921,P<0.001),preoperative Scr(0R=1,186,95%CI 1.094?1.251,P=0.009),preoperative eGFR(OR=0.918,95%CI 0.901-0.985,P=0.017),contrast medium dosage(OR=1.158,95%CI 1.061?1.965,P=0.01),PCI(OR=2.010,95%CI 1.224?3.300,P=0.018)are independent predictors of CIN occurrence,while preoperative RIPC treatment(OR=0.450,95%CI 0.203-0.731,P=0.026)is a protective factor for reducing CIN occurrence after surgery.6.No significant adverse reactions were observed during hospitalization and 6 months after CAG or PCI in patients accepting ischemic preconditioning.After 6 months of follow-up,there were no statistically significant differences in the main adverse renal events and MACE in the two groups(P>0.05).Conclusions1.Preoperative application of RIPC in patients with ACS is safe and effective,with clinical feasibility.2.RIPC can relieve the postoperative renal function damage of ACS patients undergoing CAG or PCI,reduce the incidence of CIN and the extent of renal impairment.3.History of diabetes mellitus,renal insufficiency,and dosage of contrast media were independent risk factors for CIN.Preoperative remote ischemic preconditioning is a protective factor in reducing the incidence of CIN after operation.4.RIPC can prevent CIN after PCI in patients with ACS,and its mechanism may be related to reducing the level Scr,CysC,?2-MG and NGAL.5.RIPC failed to reduce the incidence of major adverse renal events and complex cardiovascular events in ACS patients 6 months after operation. |
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