| Background and objects: In-stent restenosis(ISR)is an independent risk factor for major adverse cardiovascular events(MACE)and poor long-term prognosis.Although the prevalence of drug-eluting stents and intensive lipid-lowering therapy can significantly reduce the incidence of ISR,domestic and foreign studies show that about10% of patients will still present ISR after PCI.Apolipoprotein A-Ⅰ(apo A-Ⅰ),as the main protein component of HDL,is mainly involved in the cholesterol reverse transport and the regulation of lipid metabolism.Moreover,recent studies have shown that apo A-Ⅰ can inhibit the occurrence and development of in-stent restenosis by inhibiting inflammation,SMC proliferation,angiogenesis and platelet activation.However,there has been no clinical study on the relationship between apo A-Ⅰ and in-stent restenosis and its long-term prognosis in coronary heart disease.Whether apo A-Ⅰ has a protective effect on ISR and whether it affects the long-term prognosis of coronary heart disease after PCI remains unknown.Therefore,the objects of this study is to investigate the correlation between apo A-Ⅰ and in-stent restenosis,as well as the effect of apo A-Ⅰ on long-term clinical prognosis of patients with coronary heart disease after PCI through retrospective case-control and retrospective cohort study.Methods: This study contained two parts: Part I explored the correlation between apo A-Ⅰ and intrastent restenosis and the prediction model;Part II explored the correlation between apo A-Ⅰ and long-term clinical prognosis and the predictive value.In part Ⅰ,according to the inclusion criteria and exclusion criteria,604 patients with coronary heart disease after PCI were enrolled respectively into the study of early instent restenosis(stent implantation time ≤ 12 months)and late in-stent restenosis(stent implantation time > 12 months).In the study of early-ISR,after comparing the clinical data of ISR group and non-ISR group,univariate and multivariate Logistic regression analysis were used to explore the independent risk factors and their OR value of the early-ISR;the prediction model was established by ROC analysis,and the linear correlation of apo A-Ⅰ was explored by quartile analysis;In the study of late-ISR,the confounding factors were eliminated by correlation analysis,stratified analysis and propensity score matching(PSM),and the independent risk factors and their OR values of the late ISR were explored by univariate and multivariate Logistic regression analysis;the prediction model was established by ROC analysis,and the linear correlation of apo A-Ⅰ was explored by quartile analysis.In part Ⅱ,the homologous patient database was used from the first part,and according to the cut-off value of apo A-Ⅰ obtained in the first part of the study,the enrolled patients were divided into high apo A-Ⅰ group(apo A-Ⅰ≥ cut-off value)and low apo A-Ⅰ group(apo A-Ⅰ< cut-off value),and the PSM was used to perform 1:1 casecontrol matching,48-month major adverse cardiovascular events(MACE)were used as the study endpoint,where MACE was defined as the compound endpoint of all-cause death,recurrent myocardial infarction,and re-vascularization.Clinical outcomes of the two groups were followed up respectively.The influence of apo A-Ⅰ on long-term prognosis of coronary heart disease after PCI was investigated by univariate and multivariate Cox regression analysis.Results:Part Ⅰ Research results:(1)In the study of early-ISR,the incidence of early-ISR was8.8%.Multivariate Logistic regression analysis indicated that apo A-Ⅰ and Hb A1 c were the independent risk factors of early-ISR.The incidence of early-ISR was negatively correlated with the level of apo A-Ⅰ.The OR value of apo A-Ⅰ was 0.013.ROC analysis showed that the cut-off value of apo A-Ⅰ was 1.275 g/ L,and that of Hb A1 c was 6.63%.The input of apo A-Ⅰ and Hb A1 c level into the prediction model simultaneously could predict the incidence of early-ISR.(2)In the study of late-ISR,subgroup analysis was carried out according to the achievement of intensive lipid lowering(LDL-c ≤1.8mmol/l).In the intensive lipid-lowering subgroup,the incidence of late-ISR was15.7%;multivariate Logistic regression analysis showed that the level of apo A-Ⅰ,stent implantation time and diabetes history were independent risk factors of late-ISR,and the OR value was 0.037,1.017 and 2.853 respectively.ROC analysis showed that the cut-off value of apo A-Ⅰ was 1.275 g/L,and that of stent implantation time was 20 months.Through the prediction model of combined diagnosis of apo A-Ⅰ,stent implantation time and diabetes history,the incidence of late-ISR in patients with intensive lipid-lowering could be better predicted.In the subgroup without intensive lipid lowering,the incidence of ISR was 27.1%.The 1:1 case-control matching was conducted by propensity score.After PSM,multivariate Logistic regression analysis still indicated that apo A-Ⅰ was an independent risk factor for late-ISR,and the quartile analysis suggested that the incidence of late-ISR had a negative linear correlation with apo A-Ⅰ level.ROC analysis showed that the cut-off value of apo A-Ⅰ was 1.235g/L and the AUC was 0.756,which could be used as a considerable predictor of late-ISR.Part Ⅱ Research results: apo A-Ⅰ cut-off value(1.275g/L)from the first part of the study was used as the criteria for grouping.Patients were divided into high apo A-Ⅰgroup(≥1.275g/L)and low apo A-Ⅰ group(<1.275g/L),and then 1:1 case-control matching was performed by PSM.After matching,the median follow-up time of high apo A-I group was 43 months.The median follow-up time was 42 months in low apo AI group.The incidence of MACE was lower in the high apo A-I group than in the low apo A-I group(14.5% vs 27.1%,P=0.008),and the incidence of re-vascularization was lower than in the low apo A-I group(8.3% vs 17.9%,P=0.016),and the rates of allcause death and recurrent myocardial infarction were similar between the two groups.Univariate Cox regression analysis showed that high levels of apo A-Ⅰ(>1.275g/L)reduced the risk of MACE,while poor glycemic control(Hb A1c>6.5%)increased the incidence of MACE.Multivariate Cox regression analysis showed that high level of apo A-Ⅰ could reduce the risk of MACE after adjusting for confounding factors,and HR was 0.522.The incidence of cumulative MACE in high apo A-I group was lower than that in low apo A-Ⅰ group,and the difference was statistically significant.Conclusion: apo A-Ⅰ is an independent risk factor of ISR after PCI.The incidence of ISR is negatively correlated with the level of apo A-Ⅰ.and the anti-ISR effect of apo A-Ⅰ is not dependent on the level of HDL-c.Moreover,by the combined diagnosis of apo A-Ⅰ and clinical indicators,we can predict the incidence of early-ISR,and the lateISR in patients with intensive lipid-lowering therapies.At the same time,apo A-Ⅰ also has a certain predictive value for the long-term clinical prognosis of patients with coronary heart disease after PCI.High level of apo A-Ⅰ can reduce the risk of MACE and improve the clinical prognosis of patients. |
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