Sleep apnea (SA), which affects more than 18 million Americans, is characterized by intermittent hypoxemia and inflammation that may in turn promote atherosclerosis and cardiovascular disease (CVD). SA is associated with an increased stroke risk but its association with myocardial infarction (MI) is less clear. Moreover, results from the largest available randomized trial suggest that SA treatment reduces stroke risk but not incident coronary artery disease (CAD) risk. To explain these findings, the candidate hypothesizes that (1) SA differentially affects carotid vs. coronary atherosclerosis, which may partially explain differences in stroke vs. MI risk; and (2) SA treatment improves carotid but not coronary atherosclerosis. The R03 builds upon the candidate's K-23 project on SA and MI characteristics measured using cardiac magnetic resonance imaging (MRI). In this proposed R03 the candidate will utilize state-of-the-art hybrid Positron Emission Tomography (PET)/MR imaging in SA patients to quantify and compare atherosclerotic plaque inflammation and microcalcification in the carotid and coronary arteries before and after SA treatment (with continuous positive airway pressure [CPAP] for four months). Additionally, the candidate proposes a novel dual-tracer PET/MR approach where they will combine imaging of inflammation (using [18F]-Fluoro-2-deoxy-D-glucose [FDG]) and microcalcification (using [18F]-Sodium Fluoride [NaF]) in atherosclerotic plaques. With this novel protocol the candidate plans to assess the degree to which SA influences distinct atherosclerotic mechanistic processes. Therefore, Aim 1 will quantify and compare intraplaque inflammation in the carotid vs. coronary arteries of SA patients.
Aim 2 will quantify and compare the impact of four months of CPAP treatment on intraplaque inflammation in the carotid vs. coronary arteries of patients with SA.
Aim 3 will conduct exploratory analysis to quantify and compare intraplaque microcalcification in the carotid vs. coronary arteries in SA patients at baseline and after four months of CPAP treatment. Findings from this research may explain why SA has a stronger stroke vs. CAD effect. It may result in a paradigm shift in SA and cardiovascular disease risk with a stronger emphasis on stroke as an endpoint in clinical trials and in routine clinical care. By identifying a stronger link with carotid than coronary atherosclerosis, it may direct research to identify pathways that drive atherosclerosis processes in the two vascular beds ultimately allowing for tailored therapies for individuals at risk for these disorders, even beyond the SA setting.
The proposed R03 project uses a team science approach (multiple disciplines, i.e. cardiology, radiology, nuclear medicine, sleep medicine) and utilizes state-of-the-art vascular imaging studies with a novel dual-tracer dual-bed protocol that will for the first time, measure distinct atherosclerotic processes pre and post sleep apnea treatment. Findings from this research may explain why sleep apnea has a stronger stroke vs. myocardial infarction effect and contribute to a paradigm shift with a stronger emphasis on stroke as an endpoint in sleep apnea related clinical trials and routine clinical care. By identifying a stronger link with carotid than coronary atherosclerosis, it may direct research to identify pathways that drive atherosclerosis processes in the two vascular beds ultimately allowing for tailored therapies for individuals at risk for these disorders, even beyond the sleep apnea setting.
