Extracellular microRNA: Biomarkers of Endothelial Dysfunction in Obese Adolescents & Adults With Obstructive Sleep Apnea

Using a prospective observational approach and a clinical trial design comparing the effectiveness of continuous positive airway pressure to diet and exercise, investigators plan to evaluate how obstructive sleep apnea (OSA) leads to endothelial dysfunction in adolescents and young adults and whether treatment of OSA can improve endothelial dysfunction. Concurrently, investigators will measure miR 92a/miR 210 levels in all subjects at baseline and following therapy to determine whether miR 92a/miR 210 levels reliably predict endothelial dysfunction in patients and responses to therapy.

Investigators will randomize 100 OSA patients (age 13-21) to receive either continuous positive airway pressure (CPAP) plus baseline diet/exercise (n=50) or medical management (intensive diet and exercise; n=50). Only children in whom adenotonsillectomy is contraindicated (morbid obesity, history of adenotonsillectomy, lack of adenotonsillar hypertrophy) will be included. Investigators will conduct a randomized prospective comparative effectiveness study to assess the impact of treatment on OSA on endothelial function (peripheral arterial tonometry-EndoPAT). In addition to diagnostic polysomnography and EndoPAT at baseline, EV (extracellular vesicle) and non EV derived miR 92a/miR 210 concentrations, inflammatory cytokines concentrations, and body anthropometry will be measured. Following 3 mos of therapy and after 6mos of therapy, investigators will re-evaluate EndoPAT, EV and non EV derived miR 92a/miR 210 concentrations, inflammatory cytokines, and body anthropometry.

Throughout the study, investigators will maintain weekly telephone contact and monthly face-to-face visits as per standard of care in both groups to ensure ongoing success. In the medical management group (intensive diet and exercise), diet and exercise will be tracked by maintaining weekly telephone contact and monthly face-to-face visits with a registered dietician. For the CPAP group, investigators will also maintain weekly telephone contact and monthly face-to-face visits with a sleep technician to review mask fitting, and adherence reports, to optimize adherence to CPAP therapy.

Following completion at six months, polysomnography will be repeated.

Eligibility Criteria:
Inclusion Criteria:

* Otherwise healthy children and young adults with a diagnosis of obstructive sleep apnea based on polysomnography criteria of an obstructive apnea hypopnea index \> 10 events/hr.
* For children a BMI range up to 99.7% and for adults BMI up to 32 kg/m2 is used.

Exclusion Criteria:

* The presence of elevated blood pressure
* The presence of diabetes or pre-diabetes
* The presence of craniofacial anomalies
* The presence of neuromuscular disorders
* The presence of syndromic or defined genetic abnormalities
* Pregnancy
* History of smoking (any smoking within the prior 6 mos or \>5 pack years total)
* The presence of infectious disease (e.g. including hepatitis B, C, HIV etc.)
* The presence of collagen vascular disease (e.g. lupus, arthritis, scleroderma, polymyositis, mixed-connective tissue disease, vasculitis etc)
* The presence of hepatic disease (including hepatitis fatty liver or cirrhosis)
* The presence of renal disease (including azotemia or clinical proteinuria)
* The presence of cardiopulmonary disease (e.g. known asthma, cystic fibrosis, congenital heart disease)
* Individuals using medications which could affect sleep or breathing (including hypnotics)
* Individuals using chronic anti-inflammatory therapy
* Individuals with any subjects with acute or chronic illness.
* Individuals using anti-hypertensive therapies
* Children with a a BMI \> 99.7%
* Adults with a BMI \> 32 kg/m2