Serum concentrations of L-arginine and L-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study

Lena Vogl; Johannes Pohlhammer; Andreas Meinitzer; Barbara Rantner; Marietta Stadler; Slobodan Peric; Angelika Hammerer-Lercher; Peter Klein-Weigel; Gustav Fraedrich; Florian Kronenberg; Barbara Kollerits

doi:10.1016/j.atherosclerosis.2015.02.019

Serum concentrations of L-arginine and L-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study

Atherosclerosis. 2015 Apr;239(2):607-14. doi: 10.1016/j.atherosclerosis.2015.02.019. Epub 2015 Feb 16.

Affiliations

¹ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
² Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
³ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria; Department of Vascular Surgery, Medical University of Innsbruck, Innsbruck, Austria.
⁴ 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria; King's College London, Diabetes Research Group, London, United Kingdom.
⁵ 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria.
⁶ Central Institute of Medical and Chemical Laboratory Diagnostics, University Hospital Innsbruck, Medical University of Innsbruck, Innsbruck, Austria.
⁷ Clinic for Angiology, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
⁸ Department of Vascular Surgery, Medical University of Innsbruck, Innsbruck, Austria.
⁹ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: [email protected].

PMID: 25746168
DOI: 10.1016/j.atherosclerosis.2015.02.019

Abstract

Background: High 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.

Methods: l-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.

Results: At 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.

Conclusions: This 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.

Keywords: ADMA; Cardiovascular disease; Mortality; Peripheral arterial disease; SDMA; l-arginine; l-homoarginine.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Arginine / blood*
Austria
Biomarkers / blood
Case-Control Studies
Cause of Death
Chi-Square Distribution
Cross-Sectional Studies
Disease Progression
Homoarginine / blood*
Humans
Intermittent Claudication / blood*
Intermittent Claudication / diagnosis
Intermittent Claudication / mortality
Male
Middle Aged
Odds Ratio
Peripheral Arterial Disease / blood*
Peripheral Arterial Disease / diagnosis
Peripheral Arterial Disease / mortality
Prognosis
Proportional Hazards Models
Prospective Studies
Risk Factors
Time Factors

Substances

Biomarkers
Homoarginine
Arginine