Metabolite Patterns of Patients With Peripheral Arterial Disease In Response To Exercise

Background: The progression of peripheral arterial disease (PAD) and the metabolome’s response to supervised exercise therapy (SET) has not yet been investigated. Results: When analyzing individual time points during exercise, we found high levels of anandamide (AEA) before any exercise interventions were associated with a shorter, or worse, walking time. We also found increased arachidonic acid (AA) and decreased levels of AA precursors dihomo-γ-linolenic acid and diacylglycerol before any exercise was associated with shorter walking times. Participants who were able to tolerate large increases in AA during acute exercise had longer, or better, walking times both before and after SET. Significance: We identified two pathways of relevance to individual response to SET: AEA synthesis may increase the activity at endocannabinoid receptors, resulting in worse treadmill test performance. SET may help train patients withstand higher levels of AA and inflammatory signaling, resulting in longer walking times.