Reversibility of Cardiovascular Injury with CPAP Use: Mechanisms Involved

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DESCRIPTION (provided by applicant): The prevalence of Obstructive Sleep Apnea (OSA) in middle-aged adults is at least 4% in males and 2% in females and will probably increase with the obesity epidemic in this country. Individuals with OSA are at increased risk for fatal and non-fatal cardiovascular disease (CVD) events. Treatment with continuous positive airway pressure (CPAP) may reduce CVD risk; however, the mechanisms, time course, and durability of its benefit are not known. These are especially important issues since patients with OSA often are not compliant or are intermittently compliant with CPAP therapy. This research proposal describes our plans to evaluate the time course and magnitude of the effects of CPAP therapy on two measures of arterial function, namely arterial stiffness and endothelium-dependent vasodilation. This study has four specific aims that address four inter- related hypotheses: To determine if (i) CPAP therapy reduces carotid-to-femoral pulse wave velocity, a marker of aortic stiffness, (ii) CPAP therapy improves flow-mediated vasodilation of the brachial artery, a marker of endothelial function, (iii) the time course of changes in arterial function observed with CPAP therapy and their duration after cessation of therapy, and (iv) if coronary artery flow regulation observed in patients with OSA improves after CPAP therapy. Multimodality non-invasive cardiac and vascular imaging will be used to prospectively investigate these aims in 130 CPAP-naive adults (21-45 years old) with moderate to severe OSA, before starting CPAP therapy, after 4 and 12 weeks, and then 712 days after withdrawal. This study will have adequate power to adjust for possible confounders such as degree of obesity, sleepiness, sex, race, and CPAP compliance. This training grant and research study will provide the applicant with training and research experiences to permit her to become an independent investigator that designs and conducts rigorous patient- oriented research projects related to sleep disorders and CVD. Dr. Korcarz's long-term career goal is to be an independent investigator that performs cutting edge physiological research related to sleep disorders and cardiovascular disease risk. PUBLIC HEALTH RELEVANCE: Project Narrative Obstructive Sleep Apnea (OSA) is a treatable and highly prevalent condition that often remains underdiagnosed. OSA is linked to increased risk for fatal and non-fatal cardiovascular disease events. This proposal evaluates the effects of Continuous Positive Airway Pressure (CPAP) therapy on two measures of arterial function, specifically arterial stiffness and endothelial function, the magnitude of the effect based on duration and CPAP compliance, as well as the reversibility of it's beneficial effects after early withdrawal.