Changes And Clinical Significance Of Plasma IL-33,NF-kB And PICP Levels In Patients With Chronic Atrial Fibrillation

Objective:Atrial fibrillation（AF）is one of the most common tachyarrhythmias in clinic.Studies have shown that the prevalence of AF in the world is increasing significantly and tends to be younger.Because AF can bring a higher risk of thromboembolism and hemodynamic disorders,it is very important to explore its pathogenesis and prevent it.It has been shown that inflammatory response and inflammatory factors are involved in the pathological process of AF.Interleukin 33（IL-33）is an inflammatory factor belonging to the IL-1 family.It can activate nuclear factor kB（NF-KB）and mitogen activated protein kinase（MAPK）through the growth stimulation expression gene 2（ST2）receptor,and then promote the production of corresponding cytokines.Activated NF-KB can promote the accumulation of type I collagen.Type I collagen is an important part of cell matrix.Excessive collagen formation can lead to myocardial fibrosis.PICP is the decomposition product of type I fibrous collagen.Previous studies have shown that the levels of serum IL-33 and ST2 in patients with heart failure,chronic pulmonary heart,chronic hepatitis B and acute myocardial infarction with preserved ejection fraction are increased,and are positively correlated with the severity of the disease.Recent studies have found that the levels of serum NF-KB and PICP in patients with AF are significantly increased,and are correlated with the size of left atrium and the degree of atrial fibrosis,However,at present,the research on IL-33 in AF is very rare and inconsistent with the results obtained.The relationship between IL-33,NF-KB and PICP is not clear.Therefore,we study the role of IL-33,NF-KB and PICP in AF patients,so as to provide new diagnosis and treatment ideas for clinical treatment of AF.Method:1.Object selection According to the AF classification method of "2016 European Society of Cardiology Guidelines for the Management of AF",AF patients were divided into paroxysmal atrial fibrillation（PaAF）group,persistent AF（Persistent atrial fibrillation,Pe AF）group and permanent AF（Permanent atrial fibrillation,Pm AF）group.A total of 84 patients with non-valvular AF who were hospitalized in the Second Hospital of Jilin University from October 2020 to October 2021 were selected.There were 56 male patients and 28 female patients,aged 68.1±8.73 years.Including 32 patients in PaAF group,including 21 male patients and 11 female patients,aged 68.41±9.09years;26 patients in Pe AF group,including 18 male patients and 8 female patients,aged 66.42±10.07 years;Pm AF group,26 patients,There were 17 male patients and 9female patients,aged 69.38±6.65 years old.And 25 SR patients,including 8 male patients and 17 female patients,aged 53.64±8.24 years old,with no history of AF.This study has been reviewed by the ethics committee to ensure that the rights and safety of the subjects are protected,and the patients and their families are fully communicated and signed informed consent.Collect general information,past medical history,medication history,laboratory tests and echocardiography.Associated with valvular heart disease such as: mitral valve disease,valvular surgery;dilated cardiomyopathy,poor cardiac function（NYHA class III-IV）,recent surgical history,recent（1-3 months）acute Myocardial infarction,acute severe infection,malignant tumors of various systems,autoimmune system diseases,endocrine system diseases,etc.outside the scope of this study.2.Experimental method All the enrolled patients collected 3ml of pre-prandial venous blood after waking up in the early morning,and kept them in the anticoagulation vacuum blood collection tube.After standing for 10-20 minutes,the blood collection tube was placed in a centrifuge at 3000 rpm for 15 minutes.After centrifugation,the supernatant was placed in a 1ml centrifuge tube with a pipette,marked on the centrifuge tube,and stored in a-80°C refrigerator for cryopreservation.Plasma levels of IL-33,NF-kB and PICP were determined after 30 minutes at room temperature in the centrifuge tube.And the relevant values of the patient’s heart were detected by an experienced color Doppler.3.Statistical methods SPSS 25.0 software was used for data analysis.Measurement data conforming to normal distribution are expressed as mean ± standard deviation（?x±s）;measurement data conforming to skewed distribution are expressed as median + interquartile range[M（QR）];The ratio（%）is expressed.When comparing between groups,t test or analysis of variance should be used for data that conform to normal distribution and homogeneity of variance;rank sum test should be used for comparison of data that is not normally distributed or not conforming to homogeneity of variance analysis;comparison of enumeration data should use card square inspection.Linear correlation was used to analyze the correlation between the two groups.Logistic regression analysis was used to predict the independent risk factors of AF,and the obtained risk factors were evaluated by receiver operating characteristic（ROC）curve,and the sensitivity and specificity as well as the best predictive value were calculated.P<0.05 means the difference is statistically significant.Result:1.The plasma levels of IL-33,NF-kB and PICP in the AF group were significantly higher than those in the SR group,and the LAD in the AF group was significantly larger than that in the SR group（all P<0.05）.2.The plasma levels of IL-33,PICP and NF-kB in the Pm AF group were significantly higher than those in the PaAF group（all P<0.05）;the plasma levels of IL-33 and PICP in the Pm AF group were significantly higher than those in the Pe AF group（P<0.05）.Compared with the PaAF group,the plasma IL-33 level in the Pe AF group was significantly higher than that in the PaAF group（P<0.05）.-kB and PICP levels were not statistically different between the two groups（all P>0.05）.3.Compared with the EHRA I group,the plasma IL-33,NF-kB and PICP levels in the EHRA III group were significantly increased（all P<0.05）;The plasma level of kB was significantly increased（all P<0.05）,while there was no significant difference in the plasma level of PICP between the two groups（P>0.05）.increased（P<0.05）,while the levels of NF-kB and PICP were not significantly different between the two groups（both P>0.05）.4.There was a positive correlation between plasma IL-33 and NF-kB levels in AF group（r=0.756,P<0.05）;there was a positive correlation between IL-33 and PICP levels（r=0.479,P<0.05）;NF-kB There was a positive correlation with the level of PICP（r=0.385,P<0.05）.There was a positive correlation between plasma IL-33 level and LAD in AF group（r=0.303,p<0.05）,and a positive correlation between plasma PICP level and LAD in AF group（r=0.247,p<0.05）.5.Multivariate Logistic regression analysis showed that the odds ratio（OR）of IL-33 = 1.013,95% confidence interval（Confidence interval,CI）= 1.001-1.025),age（OR = 1.198,95% CI = 1.076-1.333）and gender（OR=0.090,95%CI=0.014-0.595）.6.The results of ROC analysis showed that the AUC of IL-33 was 0.793（95%CI=0.703-0.883）,and the AUC threshold was 294.32pg/ml（sensitivity 67.9%,specificity 88%）.Conclusion:1.IL-33,NF-KB and PICP are involved in the occurrence and development of AF.IL-33 may mediate atrial remodeling of AF through NF-KB pathway.2.IL-33,NF-KB and PICP are indicators to judge the severity of AF.3.IL-33 is an independent risk factor for predicting the occurrence of AF.