• Lena Vogl, Johannes Pohlhammer, Andreas Meinitzer, Barbara Rantner, Marietta Stadler, Slobodan Peric, Angelika Hammerer-Lercher, Peter Klein-Weigel, Gustav Fraedrich, Florian Kronenberg, and Barbara Kollerits.
• Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
• Atherosclerosis. 2015 Apr 1; 239 (2): 607-14.

BackgroundHigh serum concentrations of l-arginine and l-homoarginine increase nitric oxide (NO) availability and thereby improve endothelial function. Information about the association of these markers with peripheral arterial disease (PAD) and related outcomes is sparse.Methodsl-arginine, its metabolites and l-homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls. After the baseline investigation PAD patients were prospectively followed (median 7 years). The association of these markers with symptomatic PAD at baseline, incident cardiovascular events and all-cause mortality was assessed.ResultsAt baseline each increase of ln-l-homoarginine and l-arginine by one standard deviation was associated with symptomatic PAD: OR=0.75, 95%CI 0.59-0.96, P=0.02 and OR=1.36, 95%CI 1.07-1.73, P=0.01, respectively (both models adjusted for ln-CRP, GFR, HDL cholesterol, and current smoking). Only l-arginine remained significant after additional adjustment for ln-NT-proBNP and hs-cTnT: OR=1.49, P=0.002. In the Cox regression analysis elevated ln-l-homoarginine significantly reduced the risk to die (n=38) even independent from ln-NT-proBNP and hs-cTnT: HR=0.59, 95%CI 0.41-0.84, P=0.004. l-arginine was significantly predicting incident cardiovascular events (n=65): HR=1.68, 95%CI 1.35-2.10, P < 0.001.ConclusionsThis study in male patients with intermittent claudication and age- and diabetes-matched controls showed an association of l-homoarginine and l-arginine with PAD. During follow-up, l-arginine was associated with incident cardiovascular events probably due to its primary role in NO metabolism and impact on endothelial integrity. l-homoarginine was related to all-cause mortality implying a broader role in metabolic processes besides endothelial function.Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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