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

Kiechl, Stefan; Lee, Terry; Santer, Peter; Thompson, Graham; Tsimikas, Sotirios; Egger, Georg; Holt, David W.; Willeit, Johann; Xu, Qingbo; Mayr, Manuel

doi:10.1016/j.atherosclerosis.2008.10.040

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

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

Stefan Kiechl
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
Terry Lee
- Analytical Unit, St. George's, University of London, London, UK
Peter Santer
- Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy
Graham Thompson
- Cardiovascular Division, King's College London, London, UK
Sotirios Tsimikas
- Department of Medicine, University of California San Diego, La Jolla, USA
Georg Egger
- Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy
David W. Holt
- Analytical Unit, St. George's, University of London, London, UK
Johann Willeit
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
Qingbo Xu
- Cardiovascular Division, King's College London, London, UK
Manuel Mayr
- Cardiovascular Division, King's College London, London, UK
- Corresponding 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.

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.

Keywords: Mass spectrometry, Risk factors, Atherosclerosis, Dimethylarginines