title: Symmetric dimethylarginine, high-density lipoproteins and cardiovascular disease.
abstract: OBJECTIVE
  The vascular effects of high-density lipoproteins (HDL) differ under certain clinical conditions. The composition of HDL is modified in patients with chronic kidney disease (CKD). As a consequence, uremic HDL induces endothelial dysfunction. We have previously shown that accumulation of symmetric dimethylarginine (SDMA) in HDL causes these adverse effects of HDL in CKD. The aim of the study is to determine the impact of the accumulation of SDMA on the association between HDL and mortality.
  
  
  RESULTS
  Mortality, renal function, serum SDMA and HDL-cholesterol (HDL-C) were assessed in the LURIC study including 3310 subjects undergoing coronary angiography. All-cause mortality was 30.0% during median follow-up of 9.9 years. Serum SDMA levels significantly predicted all-cause and cardiovascular mortality, and were significantly correlated with SDMA accumulation in HDL. Notably, higher serum SDMA was independently associated with lower cholesterol efflux (P = 0.004) as a measure of HDL functionality. In subjects with low SDMA levels, higher HDL-C was associated with significantly lower mortality. In contrast, in subjects with high SDMA, HDL-C was associated with higher mortality. These findings were confirmed in 1424 participants of the MONICA/KORA S3 cohort. Of note, we derived an algorithm allowing for calculation of biologically effective HDL-C' based on measured HDL-C and SDMA. We corroborated these clinical findings with invitro evidence showing that SDMA accumulation abolishes the anti-inflammatory and regenerative properties of HDL.
  
  
  CONCLUSIONS
  The data identify SDMA as a marker of HDL dysfunction. These findings highlight on the pivotal role of SDMA accumulation in HDL as a mediator of pre-mature cardiovascular disease in patients with CKD.
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zewinger
authors.affiliation: Mannheim Medical Faculty, Medical Clinic V (Nephrology • Hypertensiology • Endocrinology • Diabetology • Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.|Institute of Nutrition, Dornburger Strasse, 07743 Friedrich Schiller University Jena, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse, 8091 Zurich, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Rohrer
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Triem
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Jennings
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Petrakis
authors.affiliation: Mannheim Medical Faculty, Medical Clinic V (Nephrology • Hypertensiology • Endocrinology • Diabetology • Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dressel
authors.affiliation: Department of Internal Medicine V, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Lepper
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz, 8036 Graz, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.affiliation: Department of Internal Medicine, Medical University of Innsbruck, Christoph-Probst-Platz, 6020 Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritsch
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstaedter Landstrasse 1, 85764 Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstaedter Landstrasse 1, 85764 Munich, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Heier
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstaedter Landstrasse 1, 85764 Munich, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II, Ingolstaedter Landstrasse 1, 85764 Munich, Germany.|Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Albert-Einstein-Allee, 89081 Ulm, Germany.
authors.forename: Tonia
authors.initials: T
authors.lastname: de Las Heras Gala
authors.affiliation: Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Albert-Einstein-Allee, 89081 Ulm, Germany.|German Centre of Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.|Deutsches Herzzentrum München, Technische Universität München, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Epidemiology and Medical Informatics, Campus Homburg/Saar, Saarland University, Institute for Medical Biometry, Kirrberger Strasse, 66421 Homburg/Saar, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagenpfeil
authors.affiliation: University Medical Center Hamburg-Eppendorf, Institute of Experimental and Clinical Pharmacology and Toxicology, Martinistrasse, 20246 Hamburg, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: University Medical Center Hamburg-Eppendorf, Institute of Experimental and Clinical Pharmacology and Toxicology, Martinistrasse, 20246 Hamburg, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: Department of Internal Medicine III, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Laufs
authors.affiliation: Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse, 8091 Zurich, Switzerland.
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.affiliation: Department of Cardiology, Charité University Hospital, Hindenburgdamm, 12203 Berlin, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: University Heart Center Zurich, Department of Cardiology, University Hospital and Center for Molecular Cardiology, University of Zurich, Rämistrasse, 8091 Zurich, Switzerland.|Center of Molecular Cardiology, University of Zurich, Wagistrasse, 8952 Zurich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Mannheim Medical Faculty, Medical Clinic V (Nephrology • Hypertensiology • Endocrinology • Diabetology • Rheumatology), University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz, 8036 Graz, Austria.|Synlab Academy, Synlab Holding Deutschland GmbH, P5, 7, 68161 Mannheim and Augsburg, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz, 8036 Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Department of Internal Medicine IV, Kirrberger Strasse, 66421 Homburg/Saar, Saarland University Medical Centre, Germany.
authors.forename: Thimoteus
authors.initials: T
authors.lastname: Speer
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000401:mortality*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D008075:Lipoproteins, HDL; C024917:symmetric dimethylarginine; D001120:Arginine
keywords: Cardiovascular risk; High-density lipoproteins; Kidney disease; Symmetric dimethylarginine