Background: Arterial stiffness is an independent determinant of cardiovascular risk. Metabolomics is the comprehensive analysis of low-molecular-weight metabolites, which could provide additional information regarding the pathogenesis of atherosclerosis. The aim of the current study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects.

Methods: We studied 42 men with symptomatic PAD (66±7 years) and 46 healthy men (66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass-spectrometry. Serum oxLDL level was measured by ELISA.

Results: The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. The aPWV correlated significantly with severeal amino acids: log-phenylalanine, log-tyrosine and log-serine for the patients with PAD. In the control group, aortic PWV was correlated to log-pyruvate. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R2=0.61; p<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R2=0.52; p<0.001).

Conclusion: Metabolomic signature of patients with advanced atherosclerosis differs compared to clinically healthy controls. The aPWV is independently associated with serum levels of Tyr and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.