Femoral arteriovenous concentration differences reveal metabolomic shifts in peripheral artery disease (PAD): A case–control study

Background: We aimed to investigate metabolomic alterations in peripheral artery disease (PAD) by analyzing blood from the femoral artery and vein, assessing metabolite release/uptake in chronically ischemic lower limbs (PAD group) and nonischemic limbs (controls), and evaluating the representativeness of upper-limb venous samples. Methods: In this exploratory case–control study, 24 patients with PAD (Fontaine IIb and III) and 18 control subjects with stable angina were enrolled. Blood was drawn from the femoral artery and vein, and the antecubital fossa. Metabolomic profiling of serum samples was performed using liquid chromatography and tandem mass spectrometry. We analyzed 560 metabolites, including amino acids and derivatives, acylcarnitines, ceramides, phosphatidylcholines, tri- and diglycerides, cholesteryl esters, sphingomyelins, and fatty acids, as well as 52 metabolic ratios/sums across various biochemical classes. Results: Femoral arteriovenous (AV) concentration differences with in-group significance in at least one group and between-group significance was observed for 47 metabolites and five metabolic sums. Among these, eight metabolic variables in antecubital vein samples were significant. Correlation between AV differences and antecubital vein samples was weak. Conclusion: Using the femoral AV concentration differences of metabolites, we identified significant local metabolomic shifts in the PAD group. Most of these changes were not revealed using traditional upper-limb venous blood sampling. Further study of AV differences could improve the understanding of the pathophysiology of PAD.