Potential Mechanism of Exercise Impairment in OSA
Condition: Obstructive Sleep Apnea
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Investigators will enroll 30 subjects with OSA (OSA group) and 30 subjects without OSA
        (control group). The detailed inclusion and exclusion criteria for subjects are listed
        below. Female subjects will be offered a urinary pregnancy test and only those documented
        to be non-pregnant will be studied.
      
Keywords: Obstructive Sleep Apnea; Vasoreactivity; Endothelial function; Exercise