Obstructive sleep apnea (OSA) is a type of disordered breathing defined by the repetitive obstruction of airflow during sleep due to upper airway collapse. Each obstructive event contributes to decreased blood oxygen, or hypoxia. OSA has been associated with various cardiovascular diseases, including hypertension, stroke, heart failure, and coronary artery disease. A factor in this association may be the decrease in blood vessel health and the marked over activation of the sympathetic nervous system that is observed in OSA due to nighttime hypoxia. The sympathetic nervous system is responsible for maintaining heart and blood vessel (cardiovascular) balance. Elevated sympathetic nervous activity (SNA) is a likely cause of hypertension and subsequent cardiovascular disease.

Continuous positive airway pressure (CPAP) therapy is the most accepted treatment for OSA and has been shown to improve high blood pressure and SNA in patients. An alternative therapy for OSA is a type of removable oral appliance known as a mandibular advancement device (MAD). Currently, there is no research directly measuring SNA in OSA patients using MADs. In addition to other cardiovascular markers, the investigators would like to directly assess SNA during a MAD intervention using the gold standard technique of microneurography. The investigators believe this will provide important information for the management of OSA, as levels of SNA are known to respond to both acute and chronic levels of hypoxia. Improved heart and blood vessel markers could further support MAD use, providing an important alternative therapy for those that can not tolerate CPAP.

In OSA the obstruction of breathing can be either partial (hypopnea) or complete (apnea), and each obstructive event contributes to decreased blood oxygen, or hypoxia. Sleep disordered breathing and nighttime hypoxia have both been identified as independent risk factors of death. Specifically, OSA is estimated to affect 34% of men and 17% of women and when inadequately treated patients present with daytime sleepiness, depression, workplace accidents and cardiovascular disease.

The severity of OSA is determined by the apnea-hypopnea index (AHI) which is the average number of airway obstructions experienced per hour of sleep. CPAP therapy has been shown to improve high blood pressure, AHI and SNA in patients. However, benefits of CPAP therapy are dose-dependent and are largely affected by patient compliance. Unfortunately, due to various discomforts associated with the use of CPAP therapy, less than fifty percent of patients adhere to long-term therapy.

MADs have increased compliance in comparison to CPAP, and improve some patient's symptoms of sleepiness. Yet, MAD interventions have shown smaller improvements in AHI values when compared to CPAP. However, AHI has been criticized for being an overly simplistic measurement of nocturnal hypoxia. In contrast, SNA is known to respond both acutely and chronically to varying levels of blood oxygen. Therefore, MAD interventions may not produce changes in AHI equal to that of a CPAP intervention; however, they may change levels of SNA and other specific CV markers of blood vessel health. This would further support the use of MADs and provide additional insight into the underlying cardiovascular mechanisms involved in OSA therapy. Understanding and validating additional therapies for OSA is of great importance, due to the significant health consequences of the disease.

Objectives

The proposed investigation aims to determine the following in mild to moderate OSA patients who fail to comply with CPAP therapy:

Does MAD therapy improve AHI in mild to moderate severity OSA?

Does MAD therapy lower basal SNA in mild to moderate severity OSA?

Does MAD therapy improve vascular function, blood pressure, heart rate variability and blood markers of elevated SNA in mild to moderate severity OSA?

Research Method/ Procedures

Methodology

To address this hypothesis, the investigators propose a prospective case series examining subjects at baseline, at 3 months and again at 6 months after a MAD intervention. A 2020 study by Ruzicka et al. found no changes in SNA after a CPAP intervention of 6 weeks. Another study by Henderson et al, 2016, found a significant reduction in SNA during a CPAP intervention of 6 months and 12 months. In 2009, Kuramoto et al measured changes in SNA indirectly during a 3 month CPAP intervention and did not see significant results. Our methodology involves direct measurement of SNA during MAD therapy, therefore, testing intervals at baseline, 3 months and 6 months of MAD therapy have been selected.

Inclusion Criteria:

• Between ages of 18-70
• Diagnosed with Obstructive Sleep Apnea and prescribed with Mandibular Advancement Device
• No medical history of cardiovascular, pulmonary, renal diseases

Exclusion Criteria:

• Any known cardiovascular, respiratory or pulmonary disease
• Have a history of smoking regularly in past 6 months
• Pre-existing symptomatic non-respiratory sleep disorder (restless leg syndrome, chronic insomnia)
• if more than 50% of their observed apneas are due to sleep apnea

Volunteers with mild to moderate OSA will be recruited with the assistance of referring dentists who are certified to provide MADs under the Alberta Dental Association & College guidelines. Participants will be included if they are between the ages of 18-70 years, initiating adjustable MAD therapy with their provider and no medical history of heart failure, cardiopulmonary and renal disease