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

 说明： 外周动脉疾病(PAD)在美国估计有1200万至1500万成年人和约20%的老年退伍军人受到影响。患有PAD的患者步态缓慢，腿部力量下降，行动不便，生活质量下降，发病率严重，经常过早死亡。据估计，超过60%的PAD患者超重或肥胖。虽然PAD本身会恶化行动能力，但肥胖会进一步增加PAD老年人的功能负担。被诊断为PAD的人也是肥胖者，他们的跛行速度通常比非肥胖者快40%，跛行后恢复需要20%的时间。对没有PAD的老年肥胖者的研究表明，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。虽然这些发现很可能适用于患有PAD的老年人，但这一假设尚未得到验证。该CDA-2旨在确定减肥和锻炼(WL+EX)与单独锻炼(EX)是否将1)比单独锻炼更大程度地改善运动功能，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运动功能变化的潜在机制。我们假设，在患有PAD的肥胖退伍军人中，减肥和运动(有氧和耐力)的联合干预将通过改善肌肉灌注量、减少炎症和减少肌肉脂肪渗透而导致运动功能的更大改善。这项为期5年的CDA-2的目标是我进行一项随机对照试验，以确定6个月的减肥和运动(WL+EX)与单纯运动(EX)对患有Fontaine II期PAD的肥胖退伍军人的功能和潜在代谢影响，以学习评估肌肉灌注、炎症和脂质渗透的技能。具体目的是：目的1：比较WL+EX和EX对退伍军人PAD患者运动功能的影响。目的：比较WL+EX和EX对肌肉血流灌注、炎症反应和脂质渗透等运动功能改变的影响。我们将对76名老年(60岁以上)肥胖退伍军人进行PAD研究。在基线测试之前，所有参与者的体重都将稳定下来。在体重稳定后，将进行基线测试，然后进行随机化。参与者将接受活动能力测试(步态速度、改良体能测试和6分钟步行距离)、步行障碍问卷、腿部肌肉力量测试(主要腿部肌肉组为1 RM)、身体成分测量(DXA和CT扫描)和肌肉灌注(增强超声造影)。肌肉活检和抽血将确定炎症水平(IL-6和肿瘤坏死因子-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，以及为期6个月的每周2次的回家步行训练。被随机分到减肥组的个人也将参加每周一次的课程，在那里他们将接受如何实施每天250-350卡路里的饮食减少的指导。后测试将在最后一轮运动后24小时进行。我们预计这项提案将表明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并减少残疾。在CDA-2中获得的技能将极大地促进我发展为一名独立的研究人员，而从这项研究中获得的信息将使我们能够制定新的临床指南，包括减轻体重，以改善患有PAD的老年退伍军人的活动功能。这些发现可能会降低PAD患者的医疗保健利用率、治疗成本以及与循环不良和活动功能障碍相关的住院费用。

 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.