Association Of Gut Microbiota Metabolites And Inflammatory Levels With Coronary Atheromatous Plaque In Acute NSTEMI Patients With Diabetes Mellitus

ObjectiveThe aim of this study is to compare the levels of serum trimethylamine oxide(TMAO)and phenylacetylglutamine(PAGln),as well as the levels of serum inflammatory indicators in two groups of people with acute non ST segment elevation myocardial infarction(NSTEMI)and acute non ST segment elevation myocardial infarction with type 2 diabetes mellitus(NSTEMI+T2DM),and to explore the correlation between these indicators and the severity of coronary atherosclerotic plaque.MethodsA total of 112 patients with acute non-ST-segment elevation myocardial infarction(NSTEMI)admitted to Fuwai Hospital Chinese Academy of Medical Sciences Shenzhen from April 2020 to April 2022 were collected.According to the history of type 2 diabetes mellitus,they were divided into NSTEMI group(n = 70),NSTEMI+T2DM group(n = 42).General data and 15 ml blood samples of all subjects were collected,of which 10 ml was used for routine laboratory biochemical index testing,including serum creatinine(Cr),high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),creatine kinase(CK),creatine kinase isoenzyme(CK-MB),D-dimer,NT-pro BNP,high-sensitivity troponin I(hs-c TNI),high-sensitivity troponin T(hs-c TNT),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL),low-density lipoprotein cholesterol(LDL),random blood glucose(Glu),glycosylated hemoglobin(Hb A1C),etc.Another 5ml of serum was obtained after centrifugation.IL-1β and HMGB1 were detected by ELISA,and intestinal metabolites TMAO and PAGln were detected by mass spectrometry multi-reaction monitoring(MRM).SYNTAX I and Gensini scoring systems were used to score the severity of coronary atherosclerotic plaque in all patients.The SYNTAX I and Gensini scores were further divided into medium-high risk(score ≥23points)and low-risk(score < 23 points).Binary logistic regression was used to analyze the correlation between serum gut microbiota metabolite levels,inflammation levels and the severity of coronary atherosclerotic plaques.ROC curves were used to assess the predictive value of PAGln and IL-1β for the severity of coronary atherosclerotic plaques.ResultsThere was no significant difference in baseline data such as gender,age,blood pressure,heart rate,medical history,and left ventricular ejection fraction between the two groups in the NSTEMI and NSTEMI + T2 DM groups(P > 0.05),nor in laboratory parameters: D-dimer,cardiac enzymes,troponin,and lipid levels(P >0.05);but random blood glucose and glycosylated hemoglobin were significantly increased in the NSTEMI + T2 DM group(P < 0.05).There was no difference in TMAO between the two groups(46.55 ± 25.89ng/ml vs 46.31 ± 25.34ng/ml)(P>0.05).However,PAGln was significantly different(15.00 ± 7.74ng/ml vs 19.44 ±9.95ng/ml)(P<0.05).There were no significant differences in hs-CRP and IL-6(P >0.05),but there were significant differences in IL-1β and HMGB1(P < 0.05)between two groups.In the NSTEMI group,the number of multiple vessel disease(MVD)cases was 22(31.43%),while in the NSTEMI+T2DM group,the number of multiple vessel disease(MVD)cases was 20(47.62%),and there was no significant difference between the two groups.There was no significant difference in SYNTAX I scores between the two groups(21.08 ± 10.45 vs 23.74 ± 12.12,P>0.05),but there was significant difference in Gensini scores(42.56 ± 25.43 vs 53.00 ± 27.39,P<0.05).Binary Logistic regression analysis showed that serum PAGln and IL-1β levels were independently correlated with Gensini high risk score after adjusting for age,sex,body mass index,diabetes history,hypertension history,smoking history,renal function,LDL and other coronary heart disease risk factors.ROC curve was used to evaluate the predictive value of PAGln and IL-1β for the severity of coronary atherosclerotic plaque by Gensini score.The AUC of PAGln and IL-1β was 0.826 and0.779,and the combined predictive AUC of both was 0.862.ConclusionCompared with NSTEMI patients,PAGln,IL-1β and HMGB1 were significantly increased in NSTEMI patients with T2 DM.PAGln and IL-1β were significantly correlated with the severity of coronary atherosclerotic plaque in NSTEMI patients and had predictive value,and the combination of them had higher predictive value.