Potential Mechanism of Exercise Impairment in OSA

Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae. A recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear. Several pathophysiologic mechanisms of OSA have been proposed and investigators hypothesize that endothelial dysfunction leading to exercise-induced right ventricular dysfunction and associated pulmonary hypertension is the potential mechanism for impaired exercise capacity in OSA.

Obstructive sleep apnea (OSA) is a common disorder with major cardiovascular sequelae, including increased systemic hypertension and strokes. OSA is highly prevalent among patients with cardiovascular disease (CVD), but OSA remains under-diagnosed, thus under-treated. Furthermore, a recent study confirmed that OSA is associated with impaired exercise capacity and increasing OSA severity predicts worsening exercise capacity, which is a marker of potential increased cardiovascular risk. However, potential mechanisms of decreased exercise capacity caused by OSA remain unclear.

Several pathophysiologic mechanisms of OSA have been proposed to explain this observation. Endothelial dysfunction is one mechanism that may result from OSA-related intermittent hypoxemia, heightened sympathetic activation, and increased blood pressure. Endothelial dysfunction is characterized by alteration of normal endothelial physiology consisting of a reduction in the bioavailability of vasodilators such as nitric oxide leading to impaired endothelium-depended vasodilation. Endothelial dysfunction has been consistently associated with an increased incidence of CVD. Recent evidence also suggests a correlation between endothelial function and exercise capacity.

In addition, endothelial dysfunction of pulmonary vasculature play an integral role in the pathogenesis of pulmonary hypertension (PH), which is defined by a mean pulmonary artery pressure exceeding 25 mm Hg. PH is associated with increased mortality and multiple morbidities including impaired exercise capacity. OSA has been formally recognized as a cause of PH by the World Health Organization (WHO) and the estimated prevalence of PH in patients with OSA is 17%. Repetitive nocturnal hypoxemia, increased sympathetic tone, and diminished endothelial dependent vaso-reactivity contribute to pulmonary artery hypoxic vasoconstriction, subsequently leading to pulmonary vasculature remodeling and PH. Recently, PH induced by exercise was described as part of the PH spectrum and may represent early, mild, PH that is still clinically relevant in many patients. To detect early PH in OSA patients may signify the importance of treatment and compliance for newly diagnosed OSA patients.

In summary, our hypothesis is that OSA patients may have endothelial dysfunction that leads to impaired exercise capacity via exercise-induced pulmonary hypertension. If our hypothesis is correct, non-invasive measurements of endothelial function could be used clinically to risk stratify patients or follow response to treatment.

Eligibility Criteria:
Inclusion Criteria:

* BMI \< 30
* OSA group: diagnosis of untreated moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥ 15 events/h).
* Control group: no OSA (AHI \< 5 events/h).

Exclusion Criteria:

* Currently using Continuous Positive Airway Pressure (CPAP) or oral appliance treatment for OSA
* Uncontrolled cardiac co-morbidity, e.g. ischemic heart disease, heart failure, or valvular heart disease that would prevent exercise
* Uncontrolled pulmonary co-morbidity, e.g. asthma or chronic obstructive pulmonary disease (COPD)
* Comorbidities that may severely impair peripheral circulation, e.g. uncontrolled diabetes mellitus, or systemic scleroderma
* Neurological conditions limiting the ability to perform walking or cycling
* Orthopedic condition limiting the ability to perform walking or cycling
* Current smokers, alcohol (\> 3 oz/day) or use of illicit drugs.
* Psychiatric disorder, other than mild and controlled depression; e.g. schizophrenia, bipolar disorder, major depression, panic or anxiety disorders.
* Pregnancy