Study On The Relationship Between Trimethylamine Oxide,a Metabolite Of Intestinal Flora,and Atrial Fibrillation And Its Prognosis

Objective:To investigate the relationship between Trimethylamine oxide(TMAO),a metabolite of intestinal flora,and Atrial fibrillation(AF)and its prognostic value in patients with AF.Methods:In this study,a total of 123 AF patients admitted to the First People’s Hospital of Zigong City from October 2019 to July 2020 were selected as the experimental group,and 41 patients with sinus rhythm who were hospitalized during the same period were selected as the control group.Liquid chromatography-tandem mass spectrometry(LC-MS/MS)was used to determine the plasma TMAO levels of the two groups of subjects.The clinical baseline data,laboratory test indicators and echocardiographic data of subjects in the two groups were recorded in detail,and the correlation between plasma TMAO level and AF-related influencing factors was analyzed.All the subjects were followed up after discharge.The primary endpoint indexes of patients between two groups—major adverse cardiovascular events(MACE)and secondary endpoint indexes(all-cause death,heart failure,cardiovascular readmission,catastrophic hemorrhage,and systemic embolism)were analyzed and compared.AF patients were divided into A,B,C and D groups according to the quartile of baseline plasma TMAO level.The risk of endpoint indicators in the four groups was analyzed by univariate and multivariate Logistic regression.The predictive value of plasma TMAO level on the prognosis of AF patients was analyzed by receiver operating characteristic(ROC)curve.Results:1.Compared with the sinus rhythm group,the plasma TMAO level in the AF group was significantly higher(P<0.05);the AF group was older(73.34±10.72 vs 66.66±9.92,P<0.05);the AF group was in patients with heart valve disease number of patients,number of patients with heart failure,uric acid level,blood creatinine level,Cystatin C(Cys-C)level,hypersensitive C-reactive protein(hs-CRP)level,D-Dimer level,brain natriuretic peptide(BNP)level,left atrial diameter(LAD)value,left ventricular end diastolic diameter(LVED)valuewas significantly higher than that of the control group(all P<0.05).The left ventricular ejection fraction(LVEF)in the AF group was significantly lower than that in the control group.Two groups of gender,smoking history,hypertension,type 2 diabetes,dilated cardiomyopathy,coronary heart disease,chronic obstructive pulmonary diseases(COPD),mixed hyperlipidemia,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),homocysteine(Hcy),red blood cell distribution width(RDW),cardiac troponin I(CTnI)were not statistically different.2.The results of multivariate logistic regression analysis showed that hs-CRP,BNP,LAD,TMAO are independent risk factors for AF.3.The plasma TMAO level in the AF group was positively correlated with age(p=0.263,P=0.003),creatinine level(ρ=0.386,P<0.001),and Cys-C(ρ=0.290,P=0.001).There is no correlation with heart valve disease,heart failure,uric acid,hs-CRP,D-dimer,BNP,LAD,LVED,LVEF(all P>0.05).4.All subjects were followed up for an average of 8.8 months after discharge.Comparative analysis of the primary endpoint of the test group and the control group:The AF group had a higher risk of MACE as the primary endpoint(RR=5.667,95%CI:1.040-33.130,P<0.05);for the secondary endpoints,the risk of heart failure(RR=6.444,95%CI:2.380-18.960,P<0.01)and cardiovascular disease readmission(RR=4.800,95%CI:2.252-11.120,P<0.01)is also significantly increased.5.According to the quartile of plasma TMAO levels,all patients with AF are divided into A(<1.74 μmol/L),B(1.74～3.27 μmol/L),C(3.28～5.13μmol/L),and D(>5.13 μmol/L).The incidence of MACE,heart failure,and cardiovascular disease readmission in all AF subjects increased with the increase of TMAO quartile level.The incidence of MACE in group D was significantly higher than that in group A(P<0.05).Compared with patients in group A,the risk of heart failure in group C and group D was significantly increased by 5.45 times(OR=5.45,95%CI:1.73-17.16,P<0.01)and 21.67 times(OR=21.67,95%CI:5.86-80.11,P<0.01);the risk of cardiovascular disease readmission for patients in group B and C was significantly increased by 3.91 times(OR=3.91,95%CI:1.26-12.16,P<0.01),8.33 Times(OR=8.33,95%CI:2.59-26.86,P<0.01).After adjusting for age,Cys-C,creatinine and other variables using a multivariate logistic regression model,AF patients with elevated plasma TMAO plasma levels,the risk of heart failure(group C OR=7.00,95%CI:1.96-24.92,P<0.01)(group D OR=24.70,95%CI:5.21-117.06,P<0.01)and cardiovascular disease readmission(group B OR=4.52,95 ^CI:1.23-16.58,P<0.05)(group C OR=9.26,95%CI:2.58-33.27,P<0.01)is still significantly increased.6.Through ROC curve analysis,the area under the curve(AUC)predicted by plasma TMAO for MACE in AF patients is 0.845(95%CI:0.763～0.927,P<0.001),the diagnostic cut-off value is 4.634μmol/L,and the sensitivity is 88.2%,the specificity is 77.4%;the AUC of plasma TMAO predicting heart failure in AF patients is 0.771(95%CI:0.686～0.856,P<0.001),the diagnostic cut-off value is 4.520μmol/L,the sensitivity is 60.3%,and the specificity is 89.2%;the predicted AUC of plasma TMAO for cardiovascular disease in AF patients was 0.835(95%CI:0.765～0.904,P<0.001),the diagnostic cut-off value was 4.454μmol/L,the sensitivity was 58.3%,and the specificity was 98.0%.Conclusions:1.The plasma TMAO level in the AF group was significantly higher than that in the sinus rhythm group.2.Independent of traditional risk factors,elevated plasma TMAO levels were a risk factor for AF.3.Plasma TMAO levels in AF patients are positively correlated with age,creatinine levels,and Cys-C levels.4.Elevated plasma TMAO levels in patients with AF have been associated with increased risk of MACE,heart failure,and cardiovascular readmission.Plasma TMAO levels perform well for predicting MACE,heart failure,and cardiovascular readmission risks in patients with AF,and can be used for prediction and risk stratification in patients with AF.