Muscle Mass and Strength Cutpoints in Persons at Risk of Mobility Disability

 描述(由申请人提供)：与年龄相关的肌肉质量和力量的丧失是导致行动不便、健康状况不佳和死亡的重要因素。重要的是要确定老年人的活动能力受限是由于肌肉质量和力量不足，因为他们可能会潜在地接受增加肌肉质量和肌肉力量的新疗法的治疗。因此，作为对RFA-AG-15-013的回应，我们召集了一个由专家和主要意见领袖组成的大型跨学科团队来开发和评估低肌肉质量和肌肉力量的诊断切入点，这些切入点预测老年人行动不便的风险增加，手术上定义为步态速度0.8米/秒。我们将分析两类研究的汇集数据，这两类研究包括大量行动不便的个人，以实现以下目标：1.对社区居住的老年人的研究，仅限于有行动不便症状的参与者；2.仔细描述心力衰竭、髋部骨折、骨关节炎或人类免疫缺陷病毒(HIV)感染的患者的临床人群，以及具有低肌肉质量、肌肉力量或行动受限的老年人的随机试验的参与者。目标1是建立和评估低肌肉质量和力量的诊断界点-分别为男性和女性-关于他们的敏感性，特异性和阳性预测值(PPV)在确定流行的和偶发的活动障碍的流行病学研究中的风险。 居住在社区的老年人行动不便的患病率高于一般人口。我们将权衡灵敏度和特异度之间的权衡，以确定瘦肉质量和强度的分界点。我们将评估各种异位测量肌肉质量、力量和体能的方法，以预测行动不便的风险。我们将评估同时包括肌肉质量和力量的复合多成分模型是否比每个单独的切割点更能预测活动能力障碍。我们将评估并存条件对肌肉质量、力量和活动度之间的关系的影响。我们还将建立肌肉质量和力量变化的切入点，最好地区分行动不便的人和没有行动不便的人。目的2将在目标1中建立的切点应用于仔细描述临床人群和随机试验的参与者，以评估他们在这些人群中的敏感性、特异性和PPV。目的3将新的切入点的灵敏度、特异度和阳性预测值与其他人先前提出的结果进行比较。我们增加了两个探索性目标：1.确定肌肉质量是否能提高切点的敏感度、特异度和PPV；2.评估各种异位测量肥胖的方法。 分界点。我们将召开一次利益攸关方协商一致会议，审查结果，以期就这些以证据为基础的切入点达成共识。该项目的发现对临床实践、公共卫生和政策以及药物开发具有重要意义。

 DESCRIPTION (provided by applicant): The age-related loss of muscle mass and strength is an important contributor to mobility disability, poor health outcomes, and death. It is important t identify older adults in whom mobility limitation is due to low muscle mass and strength because they may be potentially amenable to treatment with novel therapies that increase muscle mass and muscle strength. Accordingly, in response to RFA-AG-15-013, we have assembled a large interdisciplinary team of experts and key opinion leaders to develop and evaluate diagnostic cut-points for low muscle mass and muscle strength that predict an increased risk of mobility-disability among older adults, defined operationally as gait speed < 0.8 meters/ sec. We will analyze pooled data from two types of studies that include large number of individuals with mobility-disability to accomplish the aims listed below: 1. Studies of community-dwelling older adults, limited to participants with mobility complaints; 2. Carefully characterized clinical populations of patients with heart failure, hip fracture, osteoarthritis, or human immune-deficiency virus (HIV)-infection at risk for mobility-disability, and participants of randomized trals of older adults with low muscle mass, muscle strength or mobility limitation. Aim 1 is to develop and assess diagnostic cut-points for low muscle mass and strength - separately for men and women - with regard to their sensitivity, specificity and positive predictive value (PPV) in identifying those at risk of prevalent and incident mobility disability in epidemiologic studies of community-dwelling older adults with higher prevalence of mobility disability than the general population. We will weigh the trade-off between sensitivity and specificity in establishing cut-points for lean mass and strength. We will evaluate various approaches to allometrically scale muscle mass, strength and physical performance measures in predicting risk of mobility disability. We will evaluate whether composite, multi-component models that include both muscle mass and strength may be more predictive of mobility-disability than separate cut-points for each. We will assess the effects of comorbid conditions on the relation between muscle mass, strength, and mobility. We will also establish cut-points for change in muscle mass and strength that best discriminate those who develop mobility disability from those who do not. Aim 2 will apply the cut-points established in aim 1 to carefully characterized clinical populations an to participants of randomized trials to evaluate their sensitivity, specificity, and PPV in these populations. Aim 3 will compare the sensitivity, specificity, and positive predictive value of new cut-points with those proposed previously by others. We have added two exploratory aims to 1. determine whether consideration of muscle quality improves the sensitivity, specificity, and PPV of cut-points, and 2. evaluate various approaches to allometrically scale adiposity in establishing the cut-points. We will convene a consensus conference of stakeholders to review the results towards the goal of securing a consensus on these evidence-based cut points. The findings of this project have important implications for clinical practice, public health and policy, and drug development.