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Clinical Chemistry and Laboratory Medicine (CCLM)

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Plasma symmetric dimethylarginine reference limits from the Framingham offspring cohort

Edzard Schwedhelm1, 2 / Vanessa Xanthakis3, 5, 6 / Renke Maas4 / Lisa M. Sullivan3, 5 / Dorothee Atzler1 / Nicole Lüneburg1 / Nicole L. Glazer5, 6 / Ulrich Riederer7 / Ramachandran S. Vasan5, 6, 8 / Rainer H. Böger1, 2

1Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

2Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

3Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

4Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen, Erlangen, Germany

5Framingham Heart Study, Framingham, MA, USA

6Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA

7Institute of Pharmacy, University of Hamburg, Hamburg, Germany

8Cardiology Sections, Department of Medicine, Boston University School of Medicine, Boston, MA, USA

Corresponding author: Edzard Schwedhelm, Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Fax: 49-40-741059757

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 49, Issue 11, Pages 1907–1910, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/cclm.2011.679, August 2011

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Background: Symmetric dimethylarginine (SDMA) is a by-product of protein methylation. Once released from proteins, SDMA is eliminated by the kidneys; consequently, plasma concentration has been suggested as a sensitive marker of renal function. Furthermore, recent work implicates SDMA in the pathogenesis of cardiovascular disease. To date, reference limits for SDMA plasma concentrations in healthy individuals are lacking.

Methods: This study defined reference limits for plasma SDMA concentrations in 840 relatively healthy individuals of the Offspring Cohort from Framingham Heart Study (mean age 56 years, 61% women). Plasma SDMA concentrations were determined by LC-MS/MS using a stable isotope dilution assay.

Results: The median SDMA concentration in the reference sample was 0.37 μmol/L (Q1, Q3:0.32, 0.43 μmol/L) and the reference limits were 0.225 and 0.533 (2.5th and 97.5th percentile). In a multivariable regression model, serum creatinine, age and total homocysteine were positively associated with SDMA (p<0.001 for all), whereas the body mass index and diastolic blood pressure were inversely related to SDMA (p-values<0.01 and 0.03, respectively).

Conclusions: This study reports plasma SDMA reference limits from the community-based Framingham Heart Study. Plasma SDMA concentration was related positively to advancing age, but inversely to renal function. These reference limits may allow the identification of individuals with raised plasma SDMA concentrations.

Keywords: Framingham Heart Study; LC-MS/MS; symmetric dimethylarginine

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