The disparity in findings of these studies may stem partially from variation in patient characteristics. Most of these studies enrolled patients with conditions such as rheumatoid arthritis and Alzheimer disease, and do not account for comorbidities, such as hypercholesterolemia and chronic ischemia, which are high in these elderly populations. These conditions lead to endothelial dysfunction and increased oxidative stress that may alter the effect of NSAIDs on myocardial angiogenesis, vessel function, and perfusion. These patients may also take aspirin or other cardiovascular medications that further confound results. In this study, we used a swine model of chronic ischemia to investigate the effects of hypercholesterolemia on the cardiovascular response to the NSAID naproxen.