Obstructive sleep apnea (OSA) and hypertension are highly associated, particularly among subjects with resistant hypertension. The mechanism, however, by which the two disorders are related, remains obscure. In evaluating subjects with resistant hypertension, we observed that a large percentage subjects diagnosed with primary hyperaldosteronism (PA) were also being diagnosed with OSA. To further examine this relationship, we prospectively determined plasma renin activity and 24-hr urine aldosterone excretion in 114 subjects with resistant hypertension. In addition, subjects completed the Berlin Questionnaire, a validated instrument for identifying subjects at high risk of having OSA. Subjects at high risk of having OSA had lower plasma renin activity, significantly greater 24-hr urinary aldosterone excretion and were 2 times more likely to have been diagnosed with PA than subjects at low-risk of having OSA. Based on the strength of these results, the overall goal of the current proposal is to test the hypothesis that OSA contributes to the development of resistant hypertension by inducing hyperaldosteronism.
Specific Aim 1 : To test the hypothesis that aldosterone excretion and obstructive sleep apnea (OSA) are positively related in subjects with resistant hypertension, we will a) correlate 24-hr urinary aldosterone excretion, respiratory disturbance index and nocturnal oxygen saturation as determined during full-night polysomnographic evaluation in 190 consecutive subjects referred to UAB for resistant hypertension; and b) compare the prevalence of OSA in hypertensive subjects with confirmed primary hyperaldosteronism (PA) versus non-PA control subjects.
Specific Aim 2 : To test the hypothesis that obstructive sleep apnea stimulates aldosterone excretion, we will determine the effects of chronic OSA therapy (i.e., continuous positive airway pressure) on 24-hr urinary aldosterone excretion and known and proposed stimuli of aldosterone excretion (renin, ACTH, atrial natriuretic peptide, norepinephrine and endothelin-1) in 120 consecutive hypertensive subjects with newly diagnosed OSA. Subjects found not to have OSA will serve as controls. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL075614-02
Application #
6870236
Study Section
Special Emphasis Panel (ZRG1-CCVS (01))
Program Officer
Twery, Michael
Project Start
2004-03-15
Project End
2008-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
2
Fiscal Year
2005
Total Cost
$288,425
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
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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
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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
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 :
Pisoni, R; Acelajado, M C; Cartmill, F R et al. (2012) Long-term effects of aldosterone blockade in resistant hypertension associated with chronic kidney disease. J Hum Hypertens 26:502-6
Acelajado, Maria Czarina; Pisoni, Roberto; Dudenbostel, Tanja et al. (2012) Refractory hypertension: definition, prevalence, and patient characteristics. J Clin Hypertens (Greenwich) 14:7-12

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