Our previous work demonstrates that functional limitations associated with peripheral arterial disease (PAD) are diverse and include slower walking speed, poorer walking endurance, and impaired balance as compared to persons without PAD. Although treadmill-walking exercise improves treadmill performance in patients with intermittent claudication (IC), treadmill performance does not correlate well with community walking ability in older men and women. In older patient populations without PAD, resistance training improves functioning and walking endurance, but this mode of exercise has not been sufficiently studied in PAD. Furthermore, although 65% to 70% of men and women with PAD are either asymptomatic or have exertional leg symptoms other than IC, to our knowledge no prior studies have assessed the effects of exercise interventions in PAD patients who do not have IC. The primary aim of this study is to determine whether a six-month supervised treadmill exercise program and a supervised lower extremity progressive resistance training program, respectively, improve lower extremity functioning compared to a nutrition control group among 150 PAD patients with and without IC. We hypothesize that participants in the treadmill walking exercise program and participants in the progressive resistance training program, respectively, will experience greater improvement in functional outcomes than participants in the nutrition control group. Our primary functional outcome measures in descending order of importance are six-minute walk distance and the summary performance score. The summary performance score is a composite measure of lower extremity functioning (usual walking speed, standing balance, and time required for five repeated chair rises) measured on a 0-12 scale that predicts future risk of nursing home placement, mobility loss, and mortality. In our secondary specific aims we will identify mechanisms by which the exercise interventions improve functioning in PAD. Mechanisms we will study include changes in blood viscosity, peak oxygen consumption (VO2), calf blood flow, brachial artery endothelial reactivity, and inflammatory cytokine levels. By identifying the optimal exercise program for improving functioning in PAD patients with and without IC, our findings will have substantial clinical and public health implications for millions of patients with PAD.
