How Obesity Affects Cerebrovascular Function and the Potential Protective Effects of Novel Respiratory Muscle Training - PROJECT SUMMARY Stroke is the fourth leading cause of death in the United States. Stroke risk is associated with impaired cerebrovascular function. Younger adults with obesity have a higher risk of stroke later in life. However, the relation between obesity and cerebrovascular function is not fully elucidated. Obesity is associated with cerebrovascular dysfunction, demonstrated by impaired cerebrovascular reactivity (CVR) and reduced cerebral autoregulation (CA). However, these studies included older adults and participants with comorbidities (e.g., diabetes mellitus), potentially confounding their conclusions regarding reduced cerebrovascular function. This represents a significant knowledge gap in understanding the more direct impact of obesity on cerebrovascular function. Thus, it remains unknown whether younger adults with obesity without comorbidities exhibit reduced cerebrovascular health compared to adults without obesity. To address the first research question, cerebrovascular function will be assessed in two cohorts of otherwise healthy young adults: one with obesity and one without. Cerebrovascular function will be assessed by measuring CVR to a physiological stressor (i.e., carbon dioxide) and CA at rest. Aim 1 will test the hypothesis that individuals with obesity will have unfavorably attenuated CVR and impaired CA, indicative of reduced cerebrovascular function. Many American adults are physically inactive, failing to meet activity guidelines. This inactivity is strongly associated with developing obesity, increases the risk of stroke, and negatively impacts cerebrovascular function, leading to a reduced healthspan and lifespan. Time and facility access constraints are cited as key barriers to exercise. Thus, there is a need for time-efficient, home-based practices for improving cerebrovascular function. Inspiratory muscle strength training (IMST) is a time-efficient, home-based intervention involving breathing against resistance using a handheld device. IMST lowers blood pressure and improves peripheral vascular function, but there is limited data on IMST’s effects on cerebrovascular function. Thus, the study team will examine whether 8 weeks of IMST improves cerebrovascular function in otherwise healthy young adults with obesity. Aim 2 will test the hypothesis that IMST will favorably increase CVR and improve CA. Additionally, obesity-induced cerebrovascular dysfunction may be driven by chronic low-grade inflammation. Elevated C-reactive protein is associated with low-grade inflammation and immune dysfunction in adults with obesity, whereas limited data suggest that IMST improves immune function. Thus, exploratory aim 3 will examine the potential immunomodulatory properties of IMST in adults with obesity. The findings could have significant implications for approximately 40% of American adults with obesity, potentially offering a means to increase cerebrovascular function. This first-of-its-kind study will inform future studies among clinical populations, contribute to the growing body of literature on improving early-life vascular health, help the fellow achieve his long-term career goals in science, and contribute to the NHLBI’s mission to help people live longer, healthier, and more fulfilling lives.
