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Clinical Chemistry 53: 273-283, 2007. First published December 21, 2006; 10.1373/clinchem.2006.076711
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(Clinical Chemistry. 2007;53:273-283.)
© 2007 American Association for Clinical Chemistry, Inc.


Endocrinology and Metabolism

Asymmetrical Dimethylarginine Independently Predicts Total and Cardiovascular Mortality in Individuals with Angiographic Coronary Artery Disease (The Ludwigshafen Risk and Cardiovascular Health Study)

Andreas Meinitzer1, Ursula Seelhorst2, Britta Wellnitz2, Gabriele Halwachs-Baumann1, Bernhard O. Boehm3, Bernhard R. Winkelmann4 and Winfried März5,a

1 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
2 LURIC Database nonprofit LLC, Freiburg, Germany.
3 Division of Endocrinology, Department of Medicine, University Hospital, Ulm, Germany.
4 Cardiology Group, Frankfurt-Sachsenhausen, Germany.
5 Synlab Center of Laboratory Diagnostics Heidelberg, Heidelberg, Germany.

aAddress correspondence to this author at: Synlab Center of Laboratory Diagnostics Heidelberg, PO Box 10 47 80, D-69037 Heidelberg, Germany. Fax 0049-6221-793-111; e-mail maerz{at}synlab.de.

Background: Asymmetrical dimethylarginine (ADMA) is increased in conditions associated with increased risk of atherosclerosis. We investigated the use of ADMA to predict total and cardiovascular mortality in patients scheduled for coronary angiography.

Methods: In 2543 persons with and 695 without coronary artery disease (CAD) identified by angiography we measured ADMA and recorded total and cardiovascular mortality during a median follow-up of 5.45 years.

Results: ADMA was correlated positively to age, female sex, diabetes mellitus, former and current smoking, and C-reactive protein and inversely to HDL cholesterol and triglycerides. ADMA was not associated with body mass index, hypertension, LDL cholesterol, or the presence or absence of angiographic CAD. Glomerular filtration rate and homocysteine were the strongest predictors of ADMA. At the 2nd, 3rd and 4th quartile of ADMA, hazard ratios for all-cause mortality adjusted for age, sex, and cardiovascular risk factors were 1.12 [95% confidence interval (CI) 0.83–1.52], 1.35 (95% CI 1.01–1.81), and 1.87 (95% CI 1.43–2.44), respectively, compared with the 1st quartile. Hazard ratios for cardiovascular death were 1.13 (95% CI 0.78–1.63), 1.42 (95% CI 1.00–2.02), and 1.81 (95% CI 1.31–2.51). ADMA in the highest quartile remained predictive of mortality after accounting for medication at baseline. The predictive value of ADMA was similar to that in the entire cohort in persons with CAD, stable or unstable, but was not statistically significant in persons without angiographic CAD.

Conclusions: ADMA concentration predicts all-cause and cardiovascular mortality in individuals with CAD independently of established and emerging cardiovascular risk factors.




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