Etiology of Sleep Apnea-related Hyperaldosteronism - BP Treatment
Status:
Completed
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
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.