BCCMA: Recovery of Aged Muscle After Disuse Atrophy (REMEDY): Integrating multimorbidity, multi-omics, physiology, and biomarkers to define hospital acquired muscle atrophy and recovery (ANTICIPATE)
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Shared paragraph: The aging Veteran population has more frequent inpatient hospitalizations than non-Veteran populations. In older Veterans there is an inability to fully recover muscle mass and function after hospital- acquired weakness. The consequence of repeated periods of disuse is a hastening of the progression to disability or frailty for older Veterans. We hypothesize that anticipatory and/or early interventions are critical to maintain muscle mass and function in older Veterans. To address this hypothesis, our specific aims are to: 1) use pre- clinical models to understand biological mechanisms of failed regrowth and potential therapeutic approaches, 2) leverage precision medicine and phenotyping to predict the onset and identify risks and underlying etiology of hospital-acquired weakness in high risk Veterans with multiple morbidities, and 3) determine clinically viable methods of characterizing and monitoring disuse muscle atrophy and its impact on physical functioning and resilience. Muscle atrophy during hospitalization hastens disability leading to accelerated functional decline, decreased quality of life, and increased risk of mortality. Project 3 of REMEDY, entitled Integrating Multimorbidity, Multi- omics, Physiology, and Biomarkers to Define Hospital Acquired Muscle Atrophy and Recovery (ANTICIPATE) will leverage precision medicine and phenotyping to predict the onset and identify risks and underlying etiology of hospital-acquired weakness in older Veterans with significant multimorbidity and high risk of hospital admission. We hypothesize multi-omic, physiological, and molecular measures will augment existing health status and admission risk calculators enabling the future application of targeted interventions to prevent muscle atrophy, maintain strength, and improve recovery in high-risk Veterans. This prospective cohort will use national VA electronic health records (EHR) and clinical assessments before, during, and after hospitalization in Veterans at three diverse VA Healthcare Systems (Salt Lake City, Los Angeles, and Birmingham). The study will utilize a composite clinical and polygenic risk score developed using data from VA EHR, the Million Veteran Program (MVP), and VA-specific multimorbidity admission risk calculators to identify and characterize older Veterans who are at increased risk of hospitalization (AIM 1), determine the impact of hospitalization on muscle health and recovery in high-risk Veterans with multimorbidity (AIM 2), and identify novel biomarkers that predict hospitalization, disuse muscle atrophy, and recovery (AIM 3). Overall, as part of the collaborative REMEDY trial, ANTICIPATE will provide a novel and comprehensive screening of high risk Veterans that will be most impacted by the hospitalization. Our unique approach will detail the physiological and molecular measures before, during and after hospitalization that, when combined with the other REMEDY projects, will allow for the rigorous testing of anti-aging and muscle-centric approaches to improve recovery after hospitalization in older Veterans.
