Obstructive Sleep Apnea and Associated Pathologic Cardiovascular Phenotypes in Young Individuals: A Comprehensive and Longitudinal Analysis of At-Risk College-Aged Students

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PROJECT SUMMARY/ABSTRACT vvvvvvv Obstructive sleep apnea (OSA) is highly prevalent across the age spectrum and associated with significant cardiovascular (CV) diseases. To date, our understanding of the association between OSA and CV pathobiology comes from limited cross-sectional data examining older individuals with severe OSA and advanced CV disease, and recent clinical trials have demonstrated OSA treatment in this population does not improve CV outcomes likely because of irreversible CV pathology. The effects of incident and developing OSA on CV phenotypes in younger and healthier individuals remain unknown and whether OSA treatment in this population reverses early CV pathophysiology is uncertain. In my K23, we have demonstrated that OSA is highly prevalent in collegiate American-style football (ASF) athletes, which is a young and healthy population, but also enriched with early traditional CV risk. Our data suggest that OSA in ASF athletes is associated with maladaptive CV functional changes, reduced diastolic function and arterial stiffness; the combination which mirrors the pathophysiology of ventricular-arterial (V-A) uncoupling. New preliminary data also suggest OSA is prevalent among higher-risk female collegiate athletes. We will now leverage our access to at-risk young college-aged individuals to analyze developing OSA and the corollary impact on CV function in absence of confounding and advanced CV morbidity. The scientific premise for the proposed work lies in establishing the pathophysiology that leads to OSA- associated CV disease. Understanding the natural progression of OSA disease could lead to new and effective treatment options for healthier patients prior to irreversible CV pathology, thereby reducing the public health burden of OSA. This prospective and observational cohort study will examine young individuals with OSA using repeated measures analyses and will bring together a multi-disciplinary expert team of scientists from cardiology, exercise physiology, and sleep medicine. We will use a comprehensive array of non-invasive testing including cardiac imaging, vascular function analysis, sleep studies, and plasma metabolomics to characterize the effects of incident and developing OSA on CV function. The working hypotheses are: 1) Independent of weight gain, OSA leads to impaired diastolic function, arterial stiffening, and V-A uncoupling among at-risk young athletes and non-athlete undergraduates with OSA, 2) Changes in OSA observed in detrained individuals will remain associated with CV functional measures, independent of changes in weight, and 3) OSA leads to a specific changes in metabolism that will be associated with CV dysfunction. Aim 1 will investigate the relationship between incident OSA and diastolic function, arterial stiffness, and V-A coupling, adjusting for weight, in a large, multi-center cohort of male ASF athletes, female athletes, and undergraduate controls. Aim 2 will assess the relationship between CV dysfunction and OSA in detrained subjects adjusting for weight change and left ventricular mass regression. Aim 3 will identify the metabolic profile associated with OSA and the association between OSA-specific metabolites and early CV dysfunction.