The Cardiovascular Consequences of Sleep Apnea Plus COPD (Overlap Syndrome)

Aim 1: The Investigators will perform a cross-sectional study to examine vascular risk in individuals with OVS compared with matched individuals with OSA alone or COPD alone. The PI will examine a panel of biomarkers including cardiac magnetic resonance imaging (right ventricular mass primary outcome), flow mediated vasodilation, plasma biomarkers (BNP, troponin, hsCRP, ST2, galectin3, miR-210). This aim will allow the team to test the hypothesis that individuals with OVS have increased vascular risk compared with matched individuals with OSA alone or COPD alone. This aim will also allow the team to compare the magnitude of the effect of OSA vs. COPD vs OVS for design of subsequent basic and clinical studies. Aim 2: The Investigators will perform an interventional study in individuals with OVS to compare the impact of bi-level therapy with that of oxygen therapy (the current standard of care). The team will assess the same panel of biomarkers as in Aim 1 to determine the impact of treatment on the observed abnormalities. This aim will allow the team to test the hypothesis that bi-level therapy is superior to oxygen in the treatment of individuals with OVS from the standpoint of right ventricular mass and other cardiovascular risk parameters/outcomes. Our assessments of biomarkers will help to define potential causal pathways for our findings and will allow determination of appropriate biomarkers for subsequent multicenter studies.

6 months of Bi-Level positive airway pressure therapy starting at 8cmH2O inspiratory pressure/4 cmH2O expiratory pressure titrated until subject until the subject reaches a minimum, stable breathing pattern and blood oxygen saturation of 88%. If stability in blood oxygen content is not met using these parameters, supplemental oxygen may be added.

6 Months of Oxygen starting a minimum flow of 2 litres per minute, titrated up until the subject reaches a minimum, stable blood oxygen saturation of 88%

Brachial artery flow-mediated vasodilation (FMD, endothelium-dependent vasodilation). Highresolution brachial artery ultrasound, consisting of images taken at rest and during reactive hyperemia, will be performed under fasting conditions according to established guidelines.

Cardiac magnet resonance imaging (CMR) measurements will be obtained the same day participants undergo the evaluation of vascular reactivity measurements. Supine CMR imaging will be performed using a 3T MR scanner (GE 750, GE Healthcare) with a 16-element cardiac coil for radiofrequency signal reception.

Inclusion Criteria: BMI 24-32 OSA COPD Exclusion Criteria: Medically unstable individuals with significant neurological disease Smokers Cardiovascular disease Epworth Sleepiness score over 18 Kidney Disease