Sleep apnea is common among patients with underlying cardiovascular disease. Atherosclerosis has been suggested as an intermediary mechanism linking obstructive sleep apnea to cardiovascular disease. Although decades of evidence from observational studies suggests an independent link between sleep apnea and atherosclerosis, few have provided significant mechanistic insight regarding the role sleep apnea plays in the progression of atherosclerosis. A comprehensive assessment of the atherosclerosis cascade in sleep apnea patients, which includes endothelial dysfunction, vascular stiffness, vascular inflammation, plaque composition and total plaque burden may however help unravel this relationship in more detail. This is especially important as recent clinical trials fail to show a reduction in cardiovascular disease event risk with sleep apnea treatment using continuous positive airway pressure. Collectively, this highlights a major gap in our current knowledge about the mechanistic link between sleep apnea and atherosclerosis and continuous positive airway pressure's anti-atherosclerotic actions (or lack of). In order to fill the above-mentioned knowledge gaps, we propose a study to non-invasively quantify the entire atherosclerosis cascade including endothelial dysfunction using peripheral arterial tonometry, vascular stiffness using carotid distensibility magnetic resonance (MR) imaging (Aim 1), vascular inflammation using fluoro deoxy glucose (FDG) positron emission tomography (PET), plaque composition and total plaque burden using multi-contrast MRI (Aim 2) in sleep apnea patients using novel combined PET/MR imaging. Our group is one of the most experienced groups in this field and our study will take full advantage of this unique expertise and technology to successfully complete our goals. Our study will provide significant mechanistic insight regarding the role sleep apnea plays in the progression of atherosclerosis and regarding the anti-atherosclerotic actions of continuous positive airway pressure therapy. Furthermore, our study will risk-stratify sleep apnea patients (Aim 3) to identify those at high risk for atherosclerosis and those with the greatest anti-atherosclerotic response to continuous positive airway pressure. Future clinical trials are in need of such risk stratification of sleep apnea patients and our study will provide this crucial evidence for the next most efficient, multi-site, randomized controlled trial to investigate sleep apnea's and continuous positive airway pressure's impact on primary and secondary prevention of cardiovascular events.
Our study will non-invasively quantify the entire atherosclerosis cascade including endothelial dysfunction, vascular stiffness, vascular inflammation, plaque composition and total plaque burden in patients with sleep apnea using state-of-the-art vascular imaging. Our study will provide significant mechanistic insight regarding the role sleep apnea plays in the progression of atherosclerosis and regarding the anti-atherosclerotic actions of continuous positive airway pressure therapy. Our study will identify patients at high risk for progression of atherosclerosis and those who have the greatest anti-atherosclerotic actions of sleep apnea treatment.
