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

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