Effect of Exercise Training on Inflammation and Function in HIV Infected Veterans

运动训练对感染艾滋病毒的退伍军人炎症和功能的影响

• 批准号: 8485305
• 负责人: KRISANN K OURSLER
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8485305
• 关键词: Adult; Aerobic; Aerobic Exercise; Age; Age-Years; Aging; American; Attenuated; Biological Markers; Body Composition; CD4 Lymphocyte Count; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic; Chronically Ill; Complex; Data; Deterioration; Diastolic heart failure; EFRAC; Elderly; Exercise; Fibrosis; Foundations; Functional disorder; Future; Goals; HIV; Health; Health Personnel; Heart Rate; Heart failure; Immune; Impairment; Individual; Infection; Inflammation; Inflammatory; Life; Lifting; Mediating; Metabolic; Muscle; Muscle Weakness; Myocardium; Obesity; Organ; Outcome; Patients; Performance; Peripheral; Physical Function; Physically Handicapped; Population; Prognostic Factor; Randomized; Recommendation; Rehabilitation Research; Rehabilitation therapy; Research; Resistance; Risk; Risk Factors; Skeletal Muscle; Sports Medicine; Testing; Training; Translational Research; United States; Variant; Veterans; age effect; age related; base; college; coronary fibrosis; cytokine; deconditioning; functional decline; improved; insight; middle age; mortality; muscle form; muscle strength; novel; patient population; prevent; programs; public health relevance; rehabilitation strategy; sarcopenia; sedentary; strength training; treatment as usual; week trial

DESCRIPTION (provided by applicant): In older adults, chronic inflammation is an independent risk factor for poor physical function, muscle weakness, cardiovascular disease, and mortality. Similarly, increased levels of biomarkers of inflammation in HIV-infected adults independently predict cardiovascular disease and death, regardless of immune status. HIV-infected adults have increased risk for poor aerobic capacity, muscle weakness and sarcopenia, all of which may be accelerated by chronic inflammation. Yet, the impact of chronic inflammation on these outcomes and the effect of exercise training is not well understood. In HIV negative adults with diastolic dysfunction, biomarkers of inflammation and cardiac fibrosis predict cardiac function and mortality. In elderly HIV negative adults with diastolic dysfunction, aerobic exercise training increases aerobic capacity 16%. HIV-infected adults have a 4- fold increased risk of diastolic dysfunction. Our preliminary data indicates that diastolic dysfunction is associated with poor aerobic capacity in asymptomatic HIV-infected veterans. Exercise rehabilitation studies in younger HIV-infected adults, based on American College of Sports Medicine (ACSM) recommendations, show improvements in aerobic capacity, muscle weakness and sarcopenia but limited data are available in older HIV-infected adults. Our preliminary data shows that high-intensity aerobic exercise training in older HIV- infected adults is well tolerated and increases aerobic capacity by 17%. The effects on diastolic function, and correlates of systemic inflammation and cardiac fibrosis, are unknown in this population. The objective of this study is to determine the effect o exercise training on the central (cardiovascular) and peripheral (muscular) impairments underlying poor physical function by comparing older HIV-infected veterans randomized to combined aerobic and resistance exercise training versus usual care. Our hypothesis is that a progressive aerobic and resistance rehabilitation program will increase aerobic capacity and muscle strength, which will be mediated by improved diastolic function, increased muscle mass, and decreased systemic inflammation. To test this hypothesis, we will conduct a randomized 16-week trial of progressive aerobic and resistance training versus usual care control in 60 sedentary older (50+ years) HIV- infected veterans. We will determine the effects of exercise training on aerobic capacity and diastolic function, and their relationship to changes in biomarkers of systemic inflammation and cardiac fibrosis (AIM 1). We will also determine the effect of exercise training on strength and muscle mass, and their relationship to changes in biomarkers of systemic inflammation (AIM 2). The VA is the largest health care provider for HIV-infected individuals in the United States with over 25,000 patients, of which 64% are over 50 years of age. Findings from this novel translational research will provide the foundation for future mechanistic research to investigate organ-specific effects of exercise training, including cardiac remodeling and fibrosis, and skeletal muscle expression of inflammatory cytokines. Collectively, the proposed research will advance our goal to develop effective rehabilitation strategies that improve the health and functional independence of HIV-infected veterans. PUBLIC HEALTH RELEVANCE: Research is needed to determine safe and effective exercise rehabilitation programs to prevent and improve physical disability in older adults living with HIV. This problem is of great importance to the VA. The majority of the 25 thousand HIV-infected veterans are over 50 years of age (64%). The combined effect of aging and inflammation increase the risk for physical disability in older HIV-infected veterans. This translational exercise training trial will examine he cardiac and skeletal muscle effects of combined aerobic exercise and resistance training to attenuate the functional declines of aging with HIV by reducing the deleterious consequences of chronic inflammation. Findings will guide future rehabilitation research on cardiac remodeling and inflammation of skeletal muscle. The proposed research will advance the goal to develop effective rehabilitation strategies that improve the health of older HIV-infected veterans.

描述（由申请人提供）： 在老年人中，慢性炎症是身体功能不良、肌肉无力、心血管疾病和死亡的独立危险因素。同样，无论免疫状态如何，感染艾滋病毒的成年人炎症生物标志物水平的升高可以独立预测心血管疾病和死亡。感染艾滋病毒的成年人有氧能力差、肌肉无力和肌肉减少症的风险增加，所有这些都可能因慢性炎症而加速。然而，慢性炎症对这些结果的影响以及运动训练的效果尚不清楚。在患有舒张功能障碍的艾滋病毒阴性成年人中，炎症和心脏纤维化的生物标志物可以预测心脏功能和死亡率。对于患有舒张功能障碍的 HIV 阴性老年患者，有氧运动训练可将有氧运动能力提高 16%。感染 HIV 的成年人舒张功能障碍的风险增加 4 倍。我们的初步数据表明，舒张功能障碍与无症状艾滋病毒感染退伍军人的有氧能力差有关。根据美国运动医学会 (ACSM) 的建议，对年轻 HIV 感染者进行的运动康复研究表明，有氧能力、肌肉无力和肌肉减少症有所改善，但老年 HIV 感染者的数据有限。我们的初步数据表明，老年艾滋病毒感染者的高强度有氧运动训练具有良好的耐受性，并且可以通过以下方式提高有氧运动能力： 17%。在该人群中，对舒张功能的影响以及全身炎症和心脏纤维化的相关性尚不清楚。 本研究的目的是通过比较老年艾滋病毒感染退伍军人随机接受有氧运动和抗阻运动训练与常规护理的比较，确定运动训练对身体功能不良的中枢（心血管）和外周（肌肉）损伤的影响。我们的假设是，渐进式有氧和阻力康复计划将增加有氧能力和肌肉力量，这将通过改善舒张功能、增加肌肉质量和减少全身炎症来介导。为了检验这一假设，我们将对 60 名久坐的老年（50 岁以上）感染 HIV 的退伍军人进行一项为期 16 周的随机试验，对渐进式有氧运动和阻力训练与常规护理控制进行比较。我们将确定运动训练对有氧能力和舒张功能的影响，及其与全身炎症和心脏纤维化生物标志物变化的关系（AIM 1）。我们还将确定运动训练对力量和肌肉质量的影响，及其与全身炎症生物标志物变化的关系（AIM 2）。 VA 是美国最大的 HIV 感染者医疗保健提供者，拥有超过 25,000 名患者，其中 64% 年龄超过 50 岁。这项新颖的转化研究的结果将为未来的机制研究奠定基础，以调查运动训练的器官特异性影响，包括心脏重塑和纤维化，以及炎症细胞因子的骨骼肌表达。总的来说，拟议的研究将推进我们的目标，即制定有效的康复策略，改善感染艾滋病毒的退伍军人的健康和功能独立性。 公共卫生相关性： 需要进行研究以确定安全有效的运动康复计划，以预防和改善感染艾滋病毒的老年人的身体残疾。这个问题对于 VA 来说非常重要。 2.5 万名感染艾滋病毒的退伍军人中，大多数年龄超过 50 岁（64%）。衰老和炎症的综合影响增加了感染艾滋病毒的老年退伍军人身体残疾的风险。这项转化运动训练试验将检查有氧运动和阻力训练相结合对心脏和骨骼肌的影响，通过减少慢性炎症的有害后果来减轻艾滋病毒引起的衰老功能衰退。研究结果将指导未来关于心脏重塑和骨骼肌炎症的康复研究。拟议的研究将推进制定有效康复策略的目标，以改善感染艾滋病毒的老年退伍军人的健康。