Exercise-Induced Plasma Metabolomic Profiles in Patients With Peripheral Arterial Disease

Aim: A better knowledge of the biological consequences in the blood of these exercise-induced ischemic events in lower extremity artery disease (LEAD) may improve the prospects of disease management. We explored the preminus postexercise metabolomic difference in 39 patients with LEAD referred for a treadmill oximetry test [transcutaneous oximetry (TcPO(2))]. Methods: Ischemia was estimated through the sum of decrease from rest of oxygen pressure (DROPs) (limb TcPO(2) changes minus chest TcPO(2) changes) at buttocks, thighs, and calves regions. Targeted metabolomic analyses measuring 188 metabolites were performed on a few microliters blood samples taken at the earlobe at rest and 3 min after exercise. Results: Maximum walking distance (MWD) was 290 m (120–652 m) and ankle brachial index (ABI) was 0.67 ± 0.17. Supervised paired partial least squares discriminant analysis based on 23,345 models showed good predictive performance for test sets with a median area under the receiver operating characteristic (AUROC) curve value of 0.99 and a p-value of 0.00049. The best discriminant metabolites contributing to the model included a subset of 71 (47%) of the 150 accurately measured metabolites in the plasma, comprising 3 acylcarnitines, 3 amino acids, 5 biogenic amines, 9 sphingomyelin, 7 lysophosphatidylcholines, and 44 phosphatidylcholines. In addition, 16 of these metabolites were found to correlate with one or more severity scores of the LEAD. Conclusion: Our results provide new insights into the biological changes that accompany exercise in LEAD and contribute to a better understanding of walking impairment pathophysiology in LEAD, highlighting new candidate biomarkers.