Exercise and Weight Loss to Improve Mobility Function in Veterans with PAD

 产品说明： 外周动脉疾病（PAD）影响美国估计1200万至1500万成年人和估计20%的老年退伍军人。PAD患者行走缓慢，腿部力量下降，行动不便，生活质量下降，发病率严重，通常过早死亡。据估计，超过60%的PAD患者超重或肥胖。虽然PAD本身影响了活动能力，但肥胖给患有PAD的老年人增加了进一步的功能负担。被诊断患有PAD的肥胖个体通常比非肥胖个体跛行快40%，并且在跛行后恢复时间长20%。对无PAD的老年肥胖成年人的研究表明，运动和减肥相结合在改善身体功能、身体成分和心脏代谢风险因素方面比单独运动更有效。虽然这些发现可能转化为PAD老年人，但这一假设尚未得到验证。该CDA-2旨在确定体重减轻和运动（WL+EX）与单独运动（EX）相比，是否1）比单独运动更大程度地改善移动功能，2）通过测量肌肉微血管灌注、全身和肌肉炎症、心脏代谢风险和肌肉成分来确定移动功能变化的潜在机制。我们假设减肥和运动（有氧和阻力）的联合干预将通过改善肌肉灌注、减少炎症和减少肌肉脂肪浸润而比单独运动更大地改善患有PAD的肥胖退伍军人的运动功能。这项为期5年的CDA-2的目标是进行一项随机对照试验，以确定患有方丹II期PAD的肥胖退伍军人中6个月的减肥和运动（WL+EX）与单独运动训练（EX）的功能和潜在代谢影响，以学习评估肌肉灌注、炎症和脂质浸润的技能。具体目的是：目的1：比较WL+EX与EX对PAD退伍军人移动功能的影响。目标二：比较WL+EX与EX对运动功能变化（测量为肌肉灌注、炎症和脂质浸润）的潜在机制的影响。我们将研究76名患有PAD的老年（60岁以上）肥胖退伍军人。在基线测试之前，所有受试者的体重将保持稳定。体重稳定后，将进行基线检查，然后进行随机化。受试者将接受移动性测试（步态速度、改良体能测试和6分钟步行距离）、步行障碍问卷、下肢肌力测试（主要下肢肌肉群为1 RM）、身体成分测量（DXA和CT扫描）和肌肉灌注（超声造影）。肌肉活检和抽血将确定炎症水平（IL- 6和TNF-α）。所有参与者将在我们的诊所参加每周3次的渐进式步行和力量训练计划，并在家中步行每周2次，持续6个月。被随机分配到减肥组的个人也将参加每周的课程，在那里他们将接受如何每天减少250-350千卡饮食的指导。后测试将在最后一次运动后24小时进行。我们预计这一建议将显示出在运动计划中增加减肥计划的重要性，以改善患有PAD的肥胖退伍军人的健康状况并减少残疾。在CDA-2中获得的技能将大大提高我成为一名独立研究者的能力，而从本研究中获得的信息将使我们能够制定新的临床指南，包括减肥，以改善患有PAD的老年退伍军人的活动功能。这些发现可能会导致PAD患者的医疗保健利用率降低、治疗费用降低以及与循环不良和活动功能障碍相关的住院治疗。

 DESCRIPTION: Peripheral artery disease (PAD) affects an estimated 12 -15 million adults in the US and an estimated 20% of older Veterans. Those with PAD ambulate with slow gait and experience decreased leg strength, dysmobility, reduced quality of life, serious morbidity and often premature death. It is estimated that over 60% of individuals with PAD are overweight or obese. While PAD itself worsens mobility, obesity adds a further functional burden to older adults with PAD. Individuals diagnosed with PAD, who are also obese typically claudicate 40% more quickly than non-obese individuals and take 20% longer to recover after claudication. Studies of older obese adults without PAD have demonstrated that the combination of exercise and weight loss is more effective at improving physical function, body composition, and cardiometabolic risk factors than exercise alone. While these findings likely translate to older adults with PAD, this hypothesis has yet to be tested. This CDA-2 is designed to determine whether weight loss and exercise (WL+EX) versus exercise ( EX ) alone will 1) improve mobility function to a greater extent than exercise alone and 2) determine the mechanisms underlying changes in mobility function by measuring muscle microvascular perfusion, systemic and muscle inflammation, cardiometabolic risk, and muscle composition. We hypothesize that a combined intervention of weight loss and exercise (aerobic and resistive) will result in greater improvements in mobility function through improved muscle perfusion, reduced inflammation and reduced muscle fat infiltration than exercise alone in obese Veterans with PAD. The goals of this 5 year CDA-2 are for me to conduct a randomized controlled trial to determine the functional and underlying metabolic effects of 6 months of weight loss and exercise (WL+EX) versus exercise training alone (EX) in obese Veterans with Fontaine Stage II PAD to learn skills in the assessment of muscle perfusion, inflammation and lipid infiltration. The specific aims are: Aim 1: To compare the effects of WL+EX vs EX on mobility function in Veterans with PAD. Aim 2: To compare the effects of WL+EX vs EX on the mechanisms underlying changes in mobility function measured as muscle perfusion, inflammation and lipid infiltration. We will study 76 older (60+ years) obese Veterans with PAD. Prior to baseline testing all participants will be weight stabilized. After weight stabilization baseline testing followed by randomization will occur. Participants will undergo mobility testing (gait speed, modified physical performance test, and six minute walk distance), walking impairment questionnaires, lower extremity muscle strength testing (1RM for major lower extremity muscle groups),and measures of body composition (DXA and CT scan) and muscle perfusion (contrast enhanced ultrasonography). Muscle biopsies and blood draws will determine inflammatory levels (IL- 6 and TNF-α). All participants will participate in a gradul and progressive walking and strength training program 3x/week in our clinic and a home walking 2x/week for 6 months. Individuals randomized to the weight loss group will also attend weekly classes where they will receive instructions on how to implement a 250-350 kcal diet reduction per day. Post-testing will be done 24 hours after the last bout of exercise. We anticipate this proposal will show the importance of the addition of a weight loss program to exercise programs to improve the health and reduce disability in obese Veterans with PAD. The skills gained in this CDA-2 will greatly enhance my development into an independent investigator while the information gained from this study will allow us to make new clinical guidelines that include weight loss to improve mobility function in older Veterans with PAD. These findings may potentially result in reduced healthcare utilization, costs of treatment, and hospitalization relatd to poor circulation and mobility dysfunction in those with PAD.