The Prognostic Value Of Plasma Trimethylamine N-oxide Levels In Cerebrovascular Diseases

Background and purpose:Trimethylamine N-oxide(TMAO)is associated with cardiovascular disease and atherosclerosis.The purpose of this study was to assess the prognostic value of plasma Trimethylamine N-oxide levels in cerebralvascular diseases.1)to evaluate the association between plasma TMAO levels and acute ischemic stroke and carotid plaque stability;2)to determine whether a relatively high plasma TMAO level is associated with an increased risk of poor outcome in ischemic stroke patients.3)to investigate the relationship between the clinical outcomes and plasma TMAO concentrations in patients with acute intracerebral hemorrhage.Methods:Patients with acute ischemic stroke and cerebral hemorrhage in Huaian hospital affiliated to Xuzhou medical university from June 2017 to October 2019 were included.Plasma TMAO level was measured for all subjects after enrollment,and NIHSS score and carotid artery color doppler ultrasound were conducted,and relevant clinical and laboratory data were collected.A cross-sectional case-control study design was used to assess the differences of TMAO levels in different TOAST subtypes and the correlation between TMAO level and NIHSS score in acute ischemic stroke patients;Functional outcomes of patients with ischemic stroke and intracerebral hemorrhage were evaluated using a prospective cohort study design.Three months after the onset of stroke,the modified Rankin scale(mRS)was used to assess the clinical functional outcome,which was divided into two categories:good outcome(mRS 0-2)and poor outcome(mRS 3-6).Multivariate Logistic regression analysis was used to assess the relationship between TMAO level and poor functional outcome and death in acute ischemic stroke at 3 months.Logistic regression and Multiple-adjusted spline regression model were used to evaluate the relationship between TMAO level and functional outcome and early neurological function deterioration(END)and hematoma enlargement(HE)in patients with cerebral hemorrhage at 3 months,respectively.Results:1.The TMAO level in ischemic stroke group was higher than that in the control group,and the TMAO level was positively correlated with the NIHSS score in stroke group(r=0.523,P<0.01).There was statistically significant difference in TMAO levels in different subtypes of TOAST(P=0.003).No statistical differences were detected between the LAA subtype and CE subype and also no statistical difference between LAA subtype and SAO subtype,but there was a statistical difference between CE subtype and SAO subtype(adjusted,P=0.004).Internal carotid plaques were presented in 204 patients,and there was statistically significant differences in TMAO level between the stable plaque group and the vulnerable plaque group(P=0.004).Logistic regression analysis showed that after adjusting for potential confounders,the highest quartile of TMAO levels suggested a higher risk of vulnerable plaques(OR=4.01,95%CI 1.56-10.34,P=0.004).The optimal cutoff value of TMAO level for predicting vulnerable plaque was 5.0 μmol/L,the sensitivity and specificity were 40.9%and 83.0%,respectively.2.Of the 225 acute ischemic stroke patients included in the analysis,the median TMAO concentration was 3.8 μmol/L(interquartile range,1.9-4.8 μmol/L).At 3 months after admission,poor functional outcome was observed in 116 patients(51.6%),and 51 patients had died(22.7%).After adjusting for potential confounders,patients with TMAO levels in the highest quartile were more likely to have higher risks of poor functional outcome(compared with the lowest quartile,OR=3.63,95%CI 1.34-9.82,P=0.011)and mortality(OR=4.27,95%CI 1.07-17.07,P=0.040).3.There were 307 intracerebral hemorrhage patients(57.7%male)with a mean age of 66.8 years included in the study.The median TMAO levels was 3.2μmol/L.END,HE,and 3-month poor outcome were detected in 59(19.2%),54(17.6%),and 203(66.1%)patients,respectively.After adjusting for potential confounders,the odds ratio for the highest quartile of TMAO compared with the lowest quartile was 2.58(95%CI 1.03-6.46)for 3-month poor outcome.Furthermore,multiple-adjusted spline regression model showed a linear association between TMAO levels and poor outcome at 3 months(P=0.033 for linearity).Similar significant findings were observed when functional outcome was analysised by continuous mRS score.No association was found between TMAO levels and END and HE.Conclusion:1.TMAO levels were associated with the severity of acute ischemic stroke,and the TMAO level varies among different subtypes of ischemic stroke.TMAO levels were related to the stability of internal carotid plaque;2.Our data suggest that a high plasma TMAO level upon admission may predict unfavorable clinical outcomes in acute ischemic stroke patients;3.The present study demonstrated that increased TMAO levels were independently correlated with 3-month function outcome after intracerebral hemorrhage.