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，慢性炎症是身体机能不佳，肌肉无力，心血管疾病和死亡率的独立危险因素。同样，无论免疫状况如何，艾滋病毒感染的成年人中炎症生物标志物水平增加，可以独立预测心血管疾病和死亡。感染HIV的成年人的有氧运动能力不良，肌肉无力和肌肉减少症的风险增加，所有这些风险可能会因慢性炎症而加速。然而，慢性炎症对这些结果的影响以及运动训练的影响尚不清楚。在HIV阴性成年人中，舒张功能障碍，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。在舒张期功能障碍的老年艾滋病毒阴性成年人中，有氧运动训练增加了有氧运动能力16％。感染HIV的成年人的舒张功能障碍的风险增加了4倍。我们的初步数据表明，舒张功能障碍与无症状的HIV感染退伍军人的有氧运动能力差有关。根据美国运动医学学院（ACSM）建议，在年轻的艾滋病毒感染的成年人中进行运动康复研究，显示出有氧能力，肌肉无力和肌肉减少症的改善，但在年龄较大的HIV感染的成年人中可以使用有限的数据。我们的初步数据表明，老年艾滋病毒感染的成年人的高强度有氧运动训练良好，并通过 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是未知的。 这项研究的目的是通过比较随机将较老的HIV的退伍军人与合并的有氧运动和抵抗运动训练与通常的护理进行比较，确定对中枢（心血管）和周围（肌肉）损害的锻炼o训练的影响。我们的假设是，进行性有氧和耐药性康复计划将增加有氧运动能力和肌肉力量，这将通过改善舒张功能，肌肉质量增加和全身性炎症减少来介导。为了检验这一假设，我们将对60个久坐的较老（50岁以上）HIV感染的退伍军人进行一项随机的16周进行性有氧和抵抗训练的试验。我们将确定运动训练对有氧能力和舒张功能的影响，以及它们与系统性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，以及它们与系统性炎症生物标志物变化的关系（AIM 2）。 VA是美国艾滋病毒感染者最大的医疗保健提供者，其中25,000多名患者，其中64％超过50岁。这项新型翻译研究的结果将为未来的机械研究提供基础，以研究运动训练的器官特异性作用，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，拟议的研究将促进我们的目标，以制定有效的康复策略，以改善受HIV感染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锻炼康复计划，以预防和改善艾滋病毒携带者的身体残疾。这个问题对VA非常重要。 25,000名艾滋病毒感染的退伍军人中的大多数年龄超过50岁（64％）。衰老和炎症的综合作用增加了感染了HIV的退伍军人的身体残疾的风险。这项翻译运动训练试验将检查有氧运动和抵抗运动训练的心脏和骨骼肌效应，以减少慢性炎症的有害后果，从而减轻与HIV的功能下降。调查结果将指导对心脏重塑和骨骼肌炎症的未来康复研究。拟议的研究将促进制定有效的康复策略的目标，以改善艾滋病毒感染者的健康状况。