title: Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction.
abstract: BACKGROUND
  Risk stratification in acute myocardial infarction (MI) remains a clinical challenge. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, was investigated for its ability to assist in risk stratification for acute MI hospitalizations.
  
  
  METHODS
  TMAO was analyzed in 1079 acute MI patients. Associations with adverse outcome of all-cause mortality or reinfarction (death/MI) for shorter (6-month) and longer (2-year) terms were assessed and compared to other cohort-specific biomarkers. Added value in risk stratification by combined use with the Global Registry of Acute Coronary Events (GRACE) score was also investigated.
  
  
  RESULTS
  TMAO independently predicted death/MI at 2 years [292 events, hazard ratio 1.21 (95% CI, 1.03-1.43), P = 0.023], but was not able to predict death/MI at 6 months (161 events, P = 0.119). For death/MI at 2 years, TMAO retained independent prediction of risk (P = 0.034) and improved stratification even after addition of multiple alternative and contemporary biomarkers previously shown to provide added prognostic value in this cohort. From these contemporary biomarkers, TMAO remained the only significant predictor of outcome. Further, TMAO improved risk stratification for death/MI at 6 months by down-classifying risk in patients with GRACE score >119 and plasma TMAO concentration ≤3.7 μmol/L.
  
  
  CONCLUSIONS
  TMAO levels showed association with poor prognosis (death/MI) at 2 years and superiority over contemporary biomarkers for patients hospitalized due to acute MI. Furthermore, when used with the GRACE score for calculating risk at 6 months, TMAO reidentified patients at lower risk after initial categorization into a higher-risk group and showed usefulness as a secondary risk stratification biomarker.
authors.affiliation: Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK; ts263@le.ac.uk.|Jichi Medical University, Tochigi-ken, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Liam M
authors.initials: LM
authors.lastname: Heaney
authors.affiliation: Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.|Department of Cancer Studies, University of Leicester, RKCSB, Leicester, UK.
authors.forename: Donald J L
authors.initials: DJ
authors.lastname: Jones
authors.affiliation: Department of Cardiovascular Sciences and NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
authors.forename: Leong L
authors.initials: LL
authors.lastname: Ng
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D008744:Methylamines; C005855:trimethyloxamine