Etiology of Sleep Apnea-related Hyperaldosteronism - BP Treatment
Condition: Obstructive Sleep Apnea; Resistant Hypertension; Hyperaldosteronism
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Hypertension; Hyperaldosteronism
Study type: Interventional

Summary: 
      Hypertension affects an estimated 60-70 million Americans, predisposing them to potentially
      life threatening cardiovascular complications. Resistant hypertension, defined as
      uncontrolled blood pressure on 3 or more different antihypertensive agents, is common,
      affecting 15-20% of the entire hypertensive population or an estimated 12-14 million
      Americans. Although associated with obesity, increasing age, black race, and chronic kidney
      disease, mechanisms of treatment resistance remain obscure. The investigators' laboratory
      identified primary aldosteronism (PA) as a common cause of treatment resistance with a
      prevalence of 20% among subjects with resistant hypertension. This is clinically important
      because recognition of PA can lead to effective treatment with use of aldosterone blockers.
      Obstructive sleep apnea (OSA) is strongly associated with and predicts development of
      hypertension as demonstrated in landmark cohort studies including the Sleep Heart Health
      Study and the Wisconsin Sleep Cohort Study.

      The investigators' laboratory has confirmed OSA to be extremely common in subjects with
      resistant hypertension, with a prevalence of approximately 85%. Recognizing that PA and OSA
      are exceptionally common in subjects with resistant hypertension, the investigators
      hypothesized that the 2 may be causally related. In testing this hypothesis, the
      investigators recently reported that plasma aldosterone levels are positively correlated with
      OSA severity in subjects with resistant hypertension but not in normotensive control
      subjects. This observation suggests that there is an important mechanistic interaction
      between untreated OSA and aldosterone excess in subjects with resistant hypertension. While
      the investigators' original hypothesis was that OSA stimulates aldosterone release, the
      investigators recognize that the opposite may also be true; that is, aldosterone excess in
      subjects with resistant hypertension worsens OSA. Distinguishing between these two
      possibilities has potentially far-reaching clinical implications. If the former hypothesis is
      true, effective treatment of OSA would be expected to suppress aldosterone release in
      subjects with resistant hypertension, thereby reversing the underlying cause of their
      treatment resistance. If the latter hypothesis is true, use of mineralocorticoid receptor
      antagonists would be expected to reduce OSA severity in subjects with resistant hypertension,
      thereby enhancing treatment of OSA. Either scenario would represent a new treatment approach
      for a highly prevalent and serious medical problem.
    


Intervention name(s): Spironolactone; BP medication uptitration
Intervention type(s): Drug; Drug
Intervention description(s): antihypertensive medication added or uptitrated following standard of care
Intervention MeSH terms: Spironolactone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sleep apnea; hypertension; aldosterone; hyperaldosteronism; spironolactone; blood pressure; resistant