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
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.
- BMI < 30
- OSA group: diagnosis of untreated moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥
- Control group: no OSA (AHI < 5 events/h).
- Currently using Continuous Positive Airway Pressure (CPAP) or oral appliance treatment
- 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
- 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.