title: Incidence of all-cause and cardiovascular mortality predicted by symmetric dimethylarginine in the population-based study of health in pomerania.
abstract: BACKGROUND
  L-Arginine and its dimethylated derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been associated with cardiovascular (CV) and all-cause mortality in populations at risk. The present study aimed to investigate the prognostic value of L-arginine and its derivatives in the general population.
  
  
  RESULTS
  We evaluated 3,952 individuals (1,936 men and 2,016 women) aged 20-81 (median (IQR) 51 (37; 64) years) from the population-based Study of Health in Pomerania (SHIP). Associations of continuous [per standard deviation (SD) increase] and categorized (age- and sex-specific tertiles) serum L-arginine, ADMA, and SDMA concentrations with all-cause and cause-specific mortality were analysed. During a median (IQR) follow-up period of 10.1 (9.3; 10.8) years (38,476 person-years), 426 deaths (10.8%) were observed, including 139 CV deaths (3.5%), and 150 cancer deaths (3.8%). After multivariable adjustment, we revealed a positive association of SDMA with all-cause [hazard ratio (HR) per SD increase: 1.16, 95% confidence interval (CI): 1.07-1.25] and CV mortality [HR: 1.19, 95% CI: 1.05-1.35]. In contrast, we did not observe any association of SDMA with cancer mortality. Neither L-arginine nor ADMA were associated with all-cause or CV mortality.
  
  
  CONCLUSIONS
  SDMA, but not ADMA, is an independent predictor of all-cause and CV mortality in a large population-based cohort of European ancestry.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, Germany.
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.affiliation: Department of Internal Medicine B/Cardiology, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dörr
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany.
authors.forename: Heyo K
authors.initials: HK
authors.lastname: Kroemer
authors.affiliation: DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, Germany; Institute of Community Medicine, Department SHIP/Clinical Epidemiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site, Greifswald, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine