title: Elevated plasma dimethylglycine is a risk marker of mortality in patients with coronary heart disease.
abstract: OBJECTIVE
  To investigate whether plasma dimethylglycine was associated with and improved risk prediction of mortality among patients with coronary heart disease (CHD).
  
  
  METHODS
  By Cox modelling, we explored the association between plasma dimethylglycine and mortality in two independent cohorts of patients with suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding plasma dimethylglycine to established CHD risk factors.
  
  
  RESULTS
  Median follow-up time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across both cohorts, elevated plasma dimethylglycine levels were linearly associated with increased risk of all-cause mortality (age and gender adjusted hazard ratios (95% confidence interval, CI) were 1.72 (1.21-2.46) and 1.76 (1.42-2.18) when comparing the fourth versus the first plasma dimethylglycine quartile in patients with SAP and AMI, respectively). There was a particularly strong risk association between plasma dimethylglycine and cardiovascular, as compared with non-cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94 (1.21-3.11) and 1.43 (0.83-2.47) among patients with SAP and 1.97 (1.50-2.59) and 1.44 (1.02-2.04) among patients with AMI, respectively). The relationship between dimethylglycine and all-cause and cardiovascular mortality was only slightly attenuated in analyses adjusted for established CHD risk factors. Plasma dimethylglycine also improved risk prediction for all-cause and cardiovascular mortality, and especially among patients with AMI.
  
  
  CONCLUSIONS
  Elevated plasma dimethylglycine was associated with and improved risk prediction of mortality in patients with suspected or verified CHD. This relationship was stronger for death from cardiovascular, as compared with non-cardiovascular, causes.
authors.affiliation: Department of Clinical Science, University of Bergen, Norway gard.frodahl.svingen@helse-bergen.no.
authors.forename: Gard F T
authors.initials: GF
authors.lastname: Svingen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Hall
authors.initials: H
authors.lastname: Schartum-Hansen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Pedersen
authors.affiliation: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seifert
authors.affiliation: Norwegian Cardiovascular Disease Registry, Norwegian Institute of Public Health, Norway.
authors.forename: Marta
authors.initials: M
authors.lastname: Ebbing
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Kaare H
authors.initials: KH
authors.lastname: Bønaa
authors.affiliation: Department of Clinical Science, University of Bergen, Norway Hormone Laboratory, Haukeland University Hospital, Bergen, Norway KG Jebsen Centre for Diabetes Research, Bergen, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
authors.affiliation: Department of Clinical Science, University of Bergen, Norway Department of Cardiology, Stavanger University Hospital, Norway.
authors.forename: Dennis W T
authors.initials: DW
authors.lastname: Nilsen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Nordrehaug
authors.affiliation: Department of Rheumatology, Haukeland University Hospital, Bergen, Norway Department of Global Public Health and Primary Care, University of Bergen, Norway.
authors.forename: Jannike
authors.initials: J
authors.lastname: Øyen
authors.affiliation: Department of Clinical Science, University of Bergen, Norway Department of Heart Disease, Haukeland University Hospital, Bergen, Norway KG Jebsen Centre for Diabetes Research, Bergen, Norway.
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
mesh_terms: D060050:Angina, Stable / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D009664:Norway; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000097:blood; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C025138:dimethylglycine; C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase; D012521:Sarcosine
keywords: Angina pectoris; acute myocardial infarction; coronary heart disease; dimethylglycine; mortality