Research On The Early Warning Value Of Pericoronal Fat Attenuation Index And Fractional Flow Reserve Based On CCTA For Coronary Arteriosclerosis And Major Adverse Cardiac Events

Objective:Epicardial adipose tissue（EAT）as visceral adipose tissue,is closely adjacent to coronary artery and myocardial tissue.In recent years,evidence-based medicine has confirmed that the occurrence and development of coronary atherosclerotic heart disease（CAD）and the occurrence of various cardiovascular adverse events are closely related to EAT.EAT can secrete a large amount of anti-inflammatory or pro-inflammatory factors according to the pathophysiological process of coronary arteries.To understand the molecular mechanism of the interaction between EAT and coronary artery,can provide reference for the development of drug therapy in the future.The EAT located around the coronary arteries is called Peri-coronary adipose tissue（PCAT）,which is associated with the development of CAD and major adverse cardiovascular events.The fat attenuation index（FAI）of the PCAT is a marker of coronary artery wall inflammation.Therefore,FAI can be used to analyze inflammation quantitatively.Assessing the extent of atherosclerosis and the status of PCAT can help to reveal the role of inflammation in the formation and progression of atherosclerosis.Fractional flow reserve（FFR）is defined as the ratio of the maximum blood flow supplied to the distal end of the coronary artery with stenotic lesions to the maximum blood flow of the distal end without stenotic lesions.It is the gold standard for assessing coronary physiology currently.In clinical practice,because FFR is an invasive examination and has the disadvantage of high cost,only about 10-20%of revascularization is performed under the guidance of FFR,and clinical treatment strategies are limited.Therefore,there is an urgent need for a non-invasive functional imaging examination.Fractional flow reserve（CT-FFR）based on CCTA appears in a timely manner.It is a non-invasive method to assess the hemodynamic changes of coronary stenosis.It can identify the hemodynamic changes caused by CAD accurately and reduce the economic cost of inspection.The purpose of this study was to clarify the correlation between PCAT parameters based on Dual-layer spectrum detector CT（SDCT）and coronary stenosis,and to study the PCAT parameters of SDCT,40ke V single-level image attenuation index,slope of spectral curve,effective atomic number,and changes in epicardial fat volume,and to analyze the effect of coronary artery wall inflammation on PCAT quantitatively,and then to explore and warn the occurrence of coronary atherosclerosis,development and prognosis of the most appropriate imaging indicators of pericoronary inflammation.At the same time,CT-FFR can evaluate the functional status of coronary blood flow,and to explore whether CT-FFR and FAI combined with coronary stenosis degree can provide incremental value for the prediction performance of major adverse cardiovascular events（MACE）.Methods:1.Three groups of patients were retrospectively analyzed:the normal group,the non-significant stenosis group and the significant stenosis group（n=33 for each group）.They were randomly selected,a total of 99 people,of which the significant stenosis group received coronary angiography within 2 weeks.SDCT quantitatively evaluated the EFV and the attenuation index(FAI_40kev),the slope of the spectral curve(λ_HU),and the effective atomic number（Eff-Z）of the narrowest part of the diseased tissue.2.Patients in the significant stenosis group underwent CAG examination within 2weeks after informed consent.CAG was performed according to standard techniques.At least two views were obtained in different planes for each coronary artery.Captured images of the most severe stenosis,and assessed the severity of coronary artery stenosis（diameter reduction≥50%）by an experienced observer who knew the patient’s clinical history but was unaware of the coronary artery CTA results.3.Patients with coronary heart disease who underwent coronary CTA examination and the results showed moderate and severe lesions in one or more coronary arteries（stenosis degree of 50%to 90%）,refused the suggestion of coronary intervention and coronary artery bypass grafting,and chose oral medication were collected.At the same time,CT-FFR and FAI were measured and general clinical data were collected.All patients（157 cases）were followed up for at least 1 year.The discharge time of patients was recorded as the beginning,and the follow-up time ended in August 2021,with a follow-up period of 12-56 months,and a median follow-up of 18.2 months（interquartile range11.2-25.8 months）.Subjects developed MACE（ie,readmission for unstable angina,nonfatal myocardial infarction,revascularization,and cardiac death）as the follow-up endpoint.According to whether there was MACE or not,they were divided into MACE group and non-MACE group（there was no MACE at the end of follow-up）.4.Statistical analysis:All data of a total of 99 patients in the normal group,the non-significant stenosis group and the significant stenosis group were analyzed by SPSS20.0（IBM,Armonk,NY）and SAS 9.4（IBM,Armonk,NY）software for statistical analysis.Quantitative data were described as mean±standard deviation（SD）.Categorical variables were expressed as numbers or percentages.Multivariate analysis of variance and Duncan’s multiple range test were used to compare the basic information of the three groups.A multiple linear regression analysis was performed to evaluate the relationship between FAI_{40ke V},λ_HU,Eff-Z,EFV and significant stenosis.Z-test was used to compare AUC between models.P<0.05 was considered as statistically significant.All data were analyzed by SPSS 22.0 statistical software package.Measurement data were expressed as mean±standard deviation（x±s）;and the count data were expressed in percentage（%）.Comparison between the two groups was used two independent samples t test,χ2 test.FAI,CT-FFR,CCTA coronary stenosis degree,FAI plus coronary stenosis degree,CT-FFR plus coronary stenosis degree and FAI plus CT-FFR and coronary stenosis degree were compared between MACE group and non-MACE group.Univariate and multivariate Logistic regression analysis was performed on FAI,CT-FFR and the degree of coronary stenosis to analyze the independent risk factors of MACE.Drew receiver operating characteristic（ROC）curve to analyze the influence of FAI,CT-FFR,coronary stenosis degree,FAI plus coronary stenosis degree,CT-FFR plus coronary stenosis degree and FAI plus CT-FFR and coronary stenosis degree on major adverse cardiac events,and the predictive value of FAI plus CT-FFR and coronary stenosis degree on MACE was compared.The area under the ROC curve（AUC）was used to evaluate the diagnostic performance of FAI plus CT-FFR and coronary stenosis degree in predicting MACE.P<0.05 was considered as statistically significant.Results:1.There were significant differences in SDCT PCAT parameters(FAI_{40ke V},λ_HU,Eff-Z and EFV)among the three groups（P<0.05）.The FAI_{40ke V},λ_HU,Eff-Z in the significant stenosis group was significantly different from the normal group and the non-significant stenosis group（P<0.05）.There were statistically significant differences in FAI_{40ke V},λ_HU,Eff-Z between the non-significant stenosis group and the significant stenosis group（P<0.05）.The EFV of the normal group was significantly lower than that of the non-significant stenosis group and the significant stenosis group（P<0.001）.Univariate and multivariate logistic regression analysis determined that FAI_{40ke V}（OR=1.50,95%CI 1.01to 1.09）andλ_HU（OR=6.81,95%CI 1.87 to 24.86）were independent predictors of significant stenosis.FAI_{40ke V} andλ_HU had good discrimination,with AUC of 0.84 and 0.80,respectively.2.Compared with the non-MACE group,the triglyceride in the MACE group wasstatistically significant（P<0.05）,but the mean value was within the normal range.Through De Long test,there was no significant difference in AUC between FAI,FFR and coronary stenosis degree（all P>0.05）.The combined predictive performance of FAI,CT-FFR and coronary stenosis degree was significantly improved,and there were significant statistical differences compared with the single index and the combination of the two indexes（all P<0.05）.Conclusion:1.The PCAT parameters of SDCT change with the degree of stenosis(FAI_40kev andλ_HU decreased with the progression of stenosis,and EFV increases with the progression of stenosis in the early stage,but does not change significantly in the later stage).FAI_40kev andλ_HU are independent risk factors for severe coronary stenosis,and EFV helps to make up for the relatively insensitive PCAT index in the early stage of coronary heart disease.The PCAT parameters and EFV of SDCT may help to indicate the degree of disease progression,and may become imaging markers for the occurrence,development and prognosis of coronary heart disease.2.CCTA-based coronary stenosis,FAI and FFR are important predictors of the risk of major adverse cardiac events.CT-FFR can reflect the physiological function of coronary artery,and FAI can reflect the inflammatory state of coronary artery.CT-FFR and FAI combined with the degree of coronary stenosis can provide incremental value for predicting MACE,so as to identify high-risk patients and initiate risk reduction measures.