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

- l-homoarginine and l-arginine are associated with symptomatic PAD.
- l-homoarginine is associated with all-cause mortality and l-arginine with incident CVD.
- l-homoarginine and l-arginine show improved discriminative ability for outcomes at follow-up.

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.