High Plasma Dimethylarginine Levels are Associated with Adverse Clinical Outcome After Stroke

Hans Worthmann; Shufen Chen; Jens Martens-Lobenhoffer; Na Li; Milani Deb; Anita Blanka Tryc; Annemarie Goldbecker; Qiang Dong; Jan Thomas Kielstein; Stefanie Margarethe Bode-Böger; Karin Weissenborn

doi:10.5551/jat.8144

Original Article

High Plasma Dimethylarginine Levels are Associated with Adverse Clinical Outcome After Stroke

Hans Worthmann, Shufen Chen, Jens Martens-Lobenhoffer, Na Li, Milani Deb, Anita Blanka Tryc, Annemarie Goldbecker, Qiang Dong, Jan Thomas Kielstein, Stefanie Margarethe Bode-Böger, Karin Weissenborn

Author information

Hans Worthmann
Department of Neurology, Hannover Medical School
Shufen Chen
Department of Neurology, Hannover Medical School
Department of Neurology, Huashan Hospital, Fudan University
Jens Martens-Lobenhoffer
Department of Clinical Pharmacology, Otto-von-Guericke-University of Magdeburg, University Hospital
Na Li
Department of Neurology, Hannover Medical School
Center for Systems Neuroscience (ZSN)
Milani Deb
Department of Neurology, Hannover Medical School
Anita Blanka Tryc
Department of Neurology, Hannover Medical School
Annemarie Goldbecker
Department of Neurology, Hannover Medical School
Qiang Dong
Department of Neurology, Huashan Hospital, Fudan University
Jan Thomas Kielstein
Department of Nephrology and Hypertension, Hannover Medical School
Stefanie Margarethe Bode-Böger
Department of Clinical Pharmacology, Otto-von-Guericke-University of Magdeburg, University Hospital
Karin Weissenborn
Department of Neurology, Hannover Medical School
Center for Systems Neuroscience (ZSN)

Keywords: Asymmetric dimethylarginine(ADMA), Symmetric dimethylarginine(SDMA), L-arginine, Stroke, Outcome

JOURNAL OPEN ACCESS

2011 Volume 18 Issue 9 Pages 753-761

DOI https://doi.org/10.5551/jat.8144

View "Advance Publication" version (May 12, 2011).

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Abstract

Aim: Increased levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been observed in patients with cardiovascular risk factors and atherosclerosis and in patients with a history of stroke. The role of ADMA and its analogue symmetric dimethylarginine (SDMA) in acute ischemic stroke is yet unclear. We hypothesized that plasma dimethylarginine levels increase in the hyper-acute phase after ischemic stroke and that their time course is related to stroke outcome.
Methods: Plasma dimethylarginines ADMA and SDMA and L-arginine levels were measured in 67 patients at 6, 12, 24 hours, as well as 3 and 7 days after stroke onset using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS). Data were compared to control data from 32 age-adjusted healthy volunteers. Clinical outcome was assessed using the modified Rankin Scale (mRS) at 90 days after stroke.
Results: At baseline, plasma ADMA levels were higher in stroke patients than in controls, whereas plasma SDMA and L-arginine levels did not differ from control subjects. The time courses of ADMA and SDMA were related to the clinical outcome. Binary logistic regression analysis showed that ADMA levels of ≥ 0.566 µmol/L at day 3, ≥ 0.530 µmol/L at day 7 and SDMA levels of ≥ 0.59 µmol/L at 24 hours predicted an unfavorable clinical outcome.Conclusions: An increase of both ADMA and SDMA plasma levels within the first 72 hours after the onset of ischemic stroke predicts a poor outcome.

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