The effects of two modes of exercise training on plasma biomarkers of inflammation and oxidative stress in patients with symptomatic peripheral artery disease

University of Minnesota Ph.D. dissertation. August 2014. Major: Kinesiology. Advisors: Arthur S. Leon, MD, MS, FAHA, FACC, FACSM and Ulf G. Bronas, PhD, ATC, ATR, FSVM, FAHA. 1 computer file (PDF); x, 187 pages.Introduction: Peripheral Artery Disease (PAD) is a manifestation of progressive atherosclerosis involving the main conduit arteries supplying the lower extremities. It is well known that atherosclerotic cardiovascular disease including PAD, is related partly to vascular inflammation and oxidative stress. Treadmill walking exercise to moderate claudication pain is considered the gold standard for improving walking distance in patients with PAD and claudication. Our group had previously reported that non-ischemia inducing upper body ergometry exercise training improves pain-free and maximal walking distance similar to ischemic inducing treadmill exercise training in patients with claudication. The influence of ischemic and non-ischemic inducing exercise training on systemic inflammation and vascular oxidative stress remains to be fully elucidated. Methods: A total of 75 patients (59 male and 16 female) with symptomatic PAD from the randomized controlled trial, Exercise Training to Reduce Claudication (EXERT), were used in a secondary analysis of inflammation and oxidative stress. Analysis of plasma for TNF alpha, IL-10, and F2 Isoprostane were performed at baseline and following 12 weeks of moderate intensity, claudication inducing treadmill training (T), upper body ergometry training (UBE), or usual care (C). Analysis of covariance was used to evaluate changes among groups for all biomarkers following intervention, using baseline level as a covariate. Pearson's correlation coefficient was used to assess correlation among baseline plasma biomarkers and physical and physiological variables. Results: After 12 weeks of intervention, all patients, regardless of the group increased TNF alpha levels. In particular, patients randomized to the UBE group significantly increased TNF alpha levels compared to the control group after adjusting for baseline TNF alpha and allopurinol (a significant covariate). Participants in the treadmill group had non-significant increases in IL-10, while all groups showed non-significant decreases in F2 Isoprostanes. Additionally there was no significant correlation between baseline plasma inflammatory and oxidative stress biomarkers, with physical and physiological variables such as ankle-brachial index, pain-free walking distance, and maximal walking distance at baseline. However, body mass index was significantly correlated to baseline TNF alpha levels (r=0.228, p=0.05). Conclusion: Moderate intensity UBE training appears to significantly increase the proinflammatory cytokine TNF alpha compared to a control group in patients with symptomatic PAD. However, all groups increased TNF alpha after 12 weeks of intervention, which contradicts the deemed anti-inflammatory effect of aerobic exercise training. It is clear that further study is required to establish if exercise training in patients with claudication is anti-inflammatory