title: Symmetrical dimethylarginine predicts mortality in the general population: observations from the Dallas heart study.
abstract: OBJECTIVE
  Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years.
  
  
  RESULTS
  SDMA and ADMA were measured by liquid chromatography-tandem mass-spectrometry (n=3523), coronary artery calcium by electron-beam computed tomography, and abdominal aortic wall thickness by MRI. In unadjusted analyses, categories of increasing SDMA and ADMA were associated with higher prevalence of cardiovascular risk factors, increased risk markers, and all-cause and cardiovascular mortality (median follow-up, 7.4 years). After adjustment for age, sex, and race, traditional cardiovascular risk factors, and renal function, SDMA and ADMA analyzed as continuous variables were associated with coronary artery calcium >10, but only SDMA was associated with abdominal aortic wall thickness. SDMA, but not ADMA, was associated with cardiovascular mortality (hazard ratio per log unit change, 3.36 [95% confidence interval, 1.49-7.59]; P=0.004). SDMA and ADMA were both associated with all-cause mortality, but after further adjustment for N-terminal pro-brain-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin T, only SDMA was associated with all-cause mortality (hazard ratio per log unit change, 1.86 [95% confidence interval, 1.04-3.30]; P=0.01).
  
  
  CONCLUSIONS
  SDMA, but not ADMA, was an independent predictor of all-cause and cardiovascular mortality in a large multiethnic population-based cohort.
authors.affiliation: From the Department of Internal Medicine, Division of Cardiology (M.O.G., C.R.A., A.K., J.A.d.L., D.K.M.) and the Donald W. Reynolds Cardiovascular Clinical Research Center (C.R.A., A.K., J.A.d.L., D.K.M.), University of Texas Southwestern Medical Center, Dallas, TX; Institute of Clinical Pharmacology and Toxicology and Cardiovascular Research Center (N.L., E.S., M.A., D.A., R.H.B.), University Medical Center Hamburg-Eppendorf, and German Center for Cardiovascular Research, Partner Site Hamburg/Lübeck/Kiel (E.S., D.A., R.H.B.), Hamburg, Germany; and Leeds Institute of Genetics, Health and Therapeutics, Leeds, United Kingdom (P.J.G.).
authors.forename: M Odette
authors.initials: MO
authors.lastname: Gore
authors.forename: Nicole
authors.initials: N
authors.lastname: Lüneburg
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Maike
authors.initials: M
authors.lastname: Anderssohn
authors.forename: Amit
authors.initials: A
authors.lastname: Khera
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grant
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology
chemical_list: C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: atherosclerosis; mortality; population; risk factors