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Volume 205, Issue 1, Pages 261-265 (July 2009)


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Asymmetric and symmetric dimethylarginines are of similar predictive value for cardiovascular risk in the general population

Stefan Kiechla, Terry Leeb, Peter Santerc, Graham Thompsond, Sotirios Tsimikase, Georg Eggerf, David W. Holtb, Johann Willeita, Qingbo Xud, Manuel MayrdCorresponding Author Informationemail address

Received 29 August 2008; received in revised form 20 October 2008; accepted 30 October 2008. published online 19 December 2008.

Abstract 

Objectives

Asymmetric dimethylarginine (ADMA) has raised considerable interest, as it is an endogenous inhibitor of nitric oxide synthesis. While increased plasma levels of ADMA have been reported in different cardiovascular disease states, its association with symmetric dimethylarginine (SDMA) has not been evaluated in a prospective population-based study.

Methods and results

We performed a mass spectrometry-based analysis of ADMA and SDMA in the plasma of 572 participants of the Bruneck study. Levels of ADMA and SDMA were significantly correlated with each other (r=0.189, p<0.001). Age and parameters of renal function, however, showed a stronger influence on SDMA than on ADMA. Both ADMA and SDMA were predictive of cardiovascular disease in multivariate analysis and the associated hazard ratios over the 5-year observation period were of similar strength: 3.86 (1.36–10.9) and 7.91 (1.94–32.3) for ADMA and SDMA, respectively (p=0.011 and 0.004). Separate analyses focused on quintile groups of SDMA revealed that the increase in cardiovascular risk was mainly confined to the top category (>0.80μmol/L).

Conclusion

This study argues against an exclusive ADMA effect in mediating cardiovascular risk. Instead, SDMA, its supposedly inactive counterpart, has similar diagnostic value in this large prospective cohort.

a Department of Neurology, Medical University Innsbruck, Innsbruck, Austria

b Analytical Unit, St. George's, University of London, London, UK

c Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy

d Cardiovascular Division, King's College London, London, UK

e Department of Medicine, University of California San Diego, La Jolla, USA

f Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy

Corresponding Author InformationCorresponding author at: Cardiovascular Division, BHF Centre, King's College, University of London, 125 Coldharbour Lane, London SE5 9NU, UK. Tel.: +44 20 7848 5238; fax: +44 20 7848 5296.

PII: S0021-9150(08)00775-2

doi:10.1016/j.atherosclerosis.2008.10.040


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