We performed an exploratory analysis to evaluate the effects of a treadmill exercise program on brachial artery (BA) intima-media thickness (IMT) and three BA grayscale ultrasound measures that may indicate subclinical arterial injury. Data were from a clinical trial in individuals with peripheral artery disease who were randomly assigned to treadmill exercise training or attention control. B-mode ultrasonography was performed at baseline and after 26 weeks. BA IMT, grayscale median (GSM), entropy, and gray-level difference statistic-contrast (GLDS-CON) were measured by a single reader. The 184 participants were (mean (SD)) 66.7 (8.2) years old and had an ankle-brachial index of 0.70 (0.18). Exercise training was associated with a 0.01 (0.06) mm ( p = 0.025) reduction in BA IMT compared to 0.00 (0.05) mm ( p = 0.807) in the control group (between-group p = 0.061). BA GSM, entropy, and GLDS-CON did not change significantly with exercise. Improvements in the 6-minute walk distance correlated with increases in resting BA blood flow ( r = 0.23, p = 0.032), flow-mediated dilation ( r = 0.24, p = 0.022), diameter ( r = 0.29, p = 0.005), entropy ( r = 0.21, p = 0.047), and GLDS-CON ( r = 0.22, p = 0.041). In a post hoc analysis, BA IMT improved significantly with treadmill exercise training but did not change with attention control; however, the between-group difference did not reach statistical significance. With exercise, improvements in the 6-minute walk distance were associated with improved endothelial function, increased resting blood flow, and BA dilation, as well as higher grayscale entropy and GLDS-CON, indicating that lower extremity exercise is associated with salutary changes in upper-extremity arterial wall structure and function. ClinicalTrials.gov Identifier: NCT01408901.
Keywords: brachial artery intima-media thickness; clinical trial; duplex ultrasound; peripheral artery disease (PAD); supervised exercise therapy; ultrasound; vascular biology.