title: The Relationship Between Trimethylamine-N-Oxide and Prevalent Cardiovascular Disease in a Multiethnic Population Living in Canada.
abstract: BACKGROUND
  Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events.
  
  
  METHODS
  In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched control subjects), L-carnitine and TMAO concentrations were assessed using validated analytical approaches.
  
  
  RESULTS
  The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM. The relative levels of the samples did not appreciably change after 3 freeze-thaw cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association between L-carnitine levels and prevalent CVD was found, with adjustment for covariates (odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant, graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval, 1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol intake, the association remained significant. No significant association between carotid intimal medial thickness and L-carnitine (P = 0.64) or TMAO (P = 0.18) was found.
  
  
  CONCLUSIONS
  Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support an association between TMAO with prevalent CVD in a multiethnic population. This finding requires replication in larger studies in which dietary intake and stored serum samples exist.
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. Electronic address: Andrew.Mente@phri.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mente
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Chalcraft
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Handan
authors.initials: H
authors.lastname: Ak
authors.affiliation: Six Nations Health Services, Ohsweken, Ontario, Canada.
authors.forename: A Darlene
authors.initials: AD
authors.lastname: Davis
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Lonn
authors.affiliation: Six Nations Health Services, Ohsweken, Ontario, Canada.
authors.forename: Ruby
authors.initials: R
authors.lastname: Miller
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Murray A
authors.initials: MA
authors.lastname: Potter
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McQueen
mesh_terms: D002170:Canada; D002318:Cardiovascular Diseases / Q000097:blood* / Q000208:ethnology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D016877:Oxidants / Q000097:blood*
chemical_list: D008744:Methylamines; D016877:Oxidants; C005855:trimethyloxamine