Current U.S. Veteran demographics reveal an aging population with significant cardiovascular dysfunction. This ultimately manifests as mobility limitation, inactivity, and a subsequent worsening of cardiovascular disease (CVD) that often leads to death. However, despite this clear negative cycle of events, there is not a single clinically accepted, and therefore routinely utilized, method of assessing vascular health. As nitric oxide (NO) is anti-atherogenic and cardioprotective, identifying an in vivo bioassay of NO bioavailability has significant worth in this arena. Fueled predominantly by the VA Merit Award prior to this renewal application, single passive leg movement (sPLM) and the subsequent blood flow increase, measured non-invasively by ultrasound Doppler in the common femoral artery, is emerging as a method by which vascular endothelial function and therefore NO bioavailability can be determined. However, although this work has yielded an initial characterization of sPLM and established this method to be a novel, valid, and a clinically relevant approach to determine vascular health, further understanding of the sPLM response with advancing age and, ultimately, its implementation and assessment in both rehabilitation and clinical arenas is still necessary. With the growing interest in personalized medicine, the development of tools, such as sPLM, that allow individualized assessments to guide the physician, the patient, and the rehabilitative team, are essential. Therefore, two specific aims are proposed that will address the Central Hypothesis that the sPLM paradigm provides a clinically meaningful assessment of endothelial function. First, cardiac rehabilitation will be assessed by sPLM in the elderly, and, coupled with studies in the young, will elucidate the predominant pathways responsible for the change in endothelial function with aging and rehabilitation. Second, the CVD diagnostic value of the sPLM assessment of endothelial function will be evaluated relative to classic measures and markers of subclinical disease in order accelerate the inclusion of endothelial dysfunction as a CVD risk factor. The proposed studies aim to catalyze the transition of the assessment of endothelial function by sPLM from research to clinical practice.

Current U.S. Veteran demographics reveal an aging population with significant cardiovascular dysfunction. However, there is not a single clinically accepted, and therefore routinely utilized, method of assessing vascular health. As nitric oxide (NO) is anti-atherogenic and cardioprotective, identifying an in vivo bioassay of NO bioavailability has significant worth in this arena. Fueled predominantly by the VA Merit Award prior to this renewal application, single passive leg movement (sPLM) and the subsequent blood flow increase, measured non-invasively by ultrasound Doppler in the common femoral artery, is emerging as a method by which vascular endothelial function and therefore NO bioavailability can be determined. However, although this work has yielded an initial characterization of sPLM and established this to be a novel, valid, and a clinically relevant approach to determine vascular health, further understanding of the sPLM response with advancing age and, ultimately, its implementation and assessment in both rehabilitation and clinical arenas is still necessary.