The PREVENTABLE Physical Performance Ancillary Study

项目摘要/摘要 衰老与肌肉质量、力量和身体表现的显著下降有关，这些通常 导致残疾、丧失独立性以及包括多发病和死亡在内的不良临床后果。 目前，卫生保健提供者没有治疗方案可以为他们的患者提供延缓衰老相关的治疗方案 身体机能下降。重要的是，有证据表明他汀类药物可能是一种有效的治疗方法。 通过预防中风、心力衰竭或心肌梗死等致残事件来保持身体功能 脑梗塞。此外，他汀类药物还具有多种功效，包括抗炎、抗氧化和免疫调节。 调节作用，可以减缓或防止与衰老相关的身体机能下降。然而，有报道称 服用他汀类药物的患者肌肉疼痛和虚弱导致相当数量的患者停止服用 他汀类药物。因此，这项拟议的研究对于确定他汀类药物是否有助于保护身体功能至关重要 老年人的独立性，或者他汀类药物相关的肌肉症状是否预示着他汀类药物相关 身体机能下降。可预防的试验(U19 AG065188)提供了一个理想的机会 明确他汀类药物对衰老相关的身体功能下降的治疗效果。 可预防是一项安慰剂对照的务实临床试验，旨在调查随机化 他汀类药物可以预防痴呆症并延长2万名75岁参与者的无残疾生存期 没有临床明显的冠心病。虽然这项可预防的试验将有助于澄清 他汀类药物关于自我报告的残疾，拟议的辅助研究将延长和验证身体残疾 通过研究他汀类药物对体能变化的影响来获得数据，这些变化通常被观察到 在功能下降的轨迹中较早，并且可能是他汀类药物影响的更敏感的标志。至 确定他汀类药物是否影响体能的纵向变化，拟议的辅助药物将增加 短物理性能电池(SPPB)，这是一种经过验证的下肢性能测量方法，包括 平衡任务、4米步行和重复的椅子站立测试，在2500名可预防的患者中进行了3年以上的随访 参与者(每个干预组1,250人)。关于以患者为中心的结果的自我报告信息 身体功能，包括他汀类药物相关的肌肉症状、疲劳和疼痛也将被收集。这个 这项辅助研究的具体目的是：1)确定随机服用他汀类药物是否可以延缓衰老- 正常步态速度的相关下降；2)确定随机服用他汀类药物是否减缓了与衰老有关的下降 在下肢功能(SPPB评分)和力量(坐姿起立时间)方面；以及3)探讨随机化 他汀类药物与自我报告的他汀类药物相关的肌肉症状、疲劳和疼痛有关。通过利用 丰富的资源和可预防的基础设施，为这项及时、经济高效的研究提供了独特的 有机会显著扩大父母对自我报告的身体残疾的试验的范围和影响 通过确定他汀类药物延缓与衰老相关的体能衰退的治疗潜力。

Project Summary/Abstract Aging is associated with significant declines in muscle mass, strength, and physical performance, which often lead to disability, loss of independence, and adverse clinical outcomes including multimorbidity and mortality. At present, health care providers have no therapeutic options to offer their patients to slow aging-related declines in physical function. Importantly, evidence is emerging that statins could be an effective treatment for preserving physical function by preventing disabling events such as stroke, heart failure, or myocardial infarction. In addition, statins have pleiotropic properties including anti-inflammatory, anti-oxidant, and immuno- modulatory effects, which may slow or prevent aging-related declines in physical function. However, reports of muscle pain and weakness in patients on statins has led to a significant number of patients discontinuing statins. Thus, the proposed study is critical to establish whether statins may help to preserve physical function and independence in older adults, or whether statin-associated muscle symptoms portend a statin-related decline in physical function. The PREVENTABLE trial (U19 AG065188) provides an ideal opportunity to definitively determine the effect of statins as a treatment for aging-related declines in physical function. PREVENTABLE is a placebo-controlled pragmatic clinical trial designed to investigate whether randomization to a statin can prevent dementia and prolong disability-free survival in 20,000 participants aged 75+ years without clinically evident coronary heart disease. While the PREVENTABLE trial will help clarify the effects of statins on self-reported disability, the proposed ancillary study will extend and validate the physical disability data by investigating the effects of statins on changes in physical performance, which are typically observed earlier in the trajectory of functional decline and may be a more sensitive marker for the effects of statin. To determine if statins affect longitudinal change in physical performance, the proposed ancillary will add the Short Physical Performance Battery (SPPB), a validated measure of lower-extremity performance comprised of balance tasks, a 4-m walk, and repeated chair stand test, over 3 years of follow-up in 2,500 PREVENTABLE participants (1,250 per intervention arm). Self-reported information on patient-centered outcomes relevant to physical function including statin-associated muscle symptoms, fatigue, and pain will also be collected. The specific aims of this ancillary study are to: 1) determine whether randomization to statin slows the aging- related decline in usual gait speed; 2) determine whether randomization to statin slows aging-related declines in lower-extremity function (SPPB score) and strength (chair rise time); and 3) explore whether randomization to statin is associated with self-reported statin-associated muscle symptoms, fatigue, and pain. By leveraging the rich resources and infrastructure of PREVENTABLE, this timely and cost-effective study provides a unique opportunity to significantly expand the scope and impact of the parent trial on self-reported physical disability by determining the therapeutic potential of statins to slow aging-related declines in physical performance.