The overall goal of the current project is to determine the cause of high aldosterone levels in patients with resistant hypertension. Resistant hypertension is high blood pressure that is difficult to control even with use of multiple antihypertensive medications. This is an important medical goal as it is well documented that aldosterone excess is a common cause of resistant hypertension. Aldosterone is a steroid hormone released by the adrenal gland that raises blood pressure by causing salt and fluid retention. Aldosterone excess has been linked to obstructive sleep apnea (OSA) in patients with resistant hypertension suggesting an interaction between the 2 such that one is causing the other. However, it is not known whether the OSA is stimulating inappropriate aldosterone release in patients with resistant hypertension or whether excessive aldosterone is worsening OSA perhaps through increased fluid accumulation in the neck. The studies proposed in this application will firstly determine if untreated OSA is stimulating aldosterone release in patients with resistant hypertension by evaluating the effects of OSA treatment with continuous positive airway pressure (CPAP) on aldosterone secretion. A second set of experiments will determine if excessive aldosterone levels worsen OSA by promoting fluid retention in neck. This latter objective will be accomplished by determining the effects of blocking aldosterone with spironolactone on OSA severity as measured by overnight sleep evaluations. The role of dietary salt in potentially worsening OSA in patients with high aldosterone levels will also be investigated determining the effects of low and high dietary salt ingestion on OSA severity. The proposed studies are clinically meaningful as resistant hypertension is a common problem effecting some 10-12 million Americans. High blood pressure, if poorly controlled increases risk of heart disease, kidney damage, and stroke. If it is proven that OSA is stimulating aldosterone release, it may allow for new strategies to lower aldosterone levels by treating OSA and thereby better preventing the development of resistant hypertension. Conversely, if hyperaldosteronism is shown to worsen OSA, it may be possible to use aldosterone blockers to enhance the treatment of OSA. Both possibilities represent potentially novel opportunities to reduce risk of cardiovascular complications in patients with resistant hypertension.Project Narrative The proposed studies are clinically important in that they may allow for better control of blood pressure and/or more effective treatment of obstructive sleep apnea in patients with resistant hypertension. Both possibilities would significantly lower cardiovascular risk in patients with difficult-to-control hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL075614-08
Application #
8094513
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Twery, Michael
Project Start
2004-03-15
Project End
2014-05-31
Budget Start
2011-06-01
Budget End
2014-05-31
Support Year
8
Fiscal Year
2011
Total Cost
$326,250
Indirect Cost
Name
University of Alabama Birmingham
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Ghazi, Lama; Dudenbostel, Tanja; Xing, Daisy et al. (2017) Assessment of vascular function in low socioeconomic status preschool children: a pilot study. J Am Soc Hypertens 11:101-109
Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A (2016) Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure. Can J Cardiol 32:603-6
Dudenbostel, Tanja; Ghazi, Lama; Liu, Mingchun et al. (2016) Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension. Hypertension 68:995-1003
Ghazi, Lama; Dudenbostel, Tanja; Lin, Chee Paul et al. (2016) Urinary sodium excretion predicts blood pressure response to spironolactone in patients with resistant hypertension independent of aldosterone status. J Hypertens 34:1005-10
Dudenbostel, Tanja; Siddiqui, Mohammed; Oparil, Suzanne et al. (2016) Refractory Hypertension: A Novel Phenotype of Antihypertensive Treatment Failure. Hypertension 67:1085-92
Egan, Brent M; Zhao, Yumin; Li, Jiexiang et al. (2014) Response to Comment on optimal treatment for resistant hypertension: the missing data on pulse wave velocity. Hypertension 63:e17-8
Pimenta, Eduardo; Stowasser, Michael; Gordon, Richard D et al. (2013) Increased dietary sodium is related to severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism. Chest 143:978-983
Dudenbostel, T (2013) Resistant hypertension-complex mix of secondary causes and comorbidities. J Hum Hypertens :
Dudenbostel, Tanja; Glasser, Stephen P (2012) Effects of antihypertensive drugs on arterial stiffness. Cardiol Rev 20:259-63
Pimenta, Eduardo; Calhoun, David A (2012) Resistant hypertension: incidence, prevalence, and prognosis. Circulation 125:1594-6

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