This Article Full Text Full Text (PDF) All Versions of this Article: 43/3/518    most recent 01.HYP.0000116223.97436.e5v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goodfriend, T. L. Articles by Calhoun, D. A. Search for Related Content PubMed PubMed Citation Articles by Goodfriend, T. L. Articles by Calhoun, D. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Obesity Sleep Apnea Related Collections Obesity Cardiovascular Pharmacology Other hypertension Lipid and lipoprotein metabolism Oxidant stress

(Hypertension. 2004;43:518.)
© 2004 American Heart Association, Inc.

Hypertension Grand Rounds

Resistant Hypertension, Obesity, Sleep Apnea, and Aldosterone

Theory and Therapy

From William S. Middleton Memorial Veterans Hospital (T.L.G.) and Departments of Medicine and Pharmacology (T.L.G.), University of Wisconsin, Madison; and Vascular Biology and Hypertension Program (D.A.C.), University of Alabama at Birmingham.

Correspondence to Theodore L. Goodfriend, Research Service, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI 53705. E-mail tgoodfri{at}facstaff.wisc.edu

Hypertension resistant to 2 antihypertensive drugs is more common among obese patients than among lean patients. The case we describe and the observations we report suggest that refractoriness among obese hypertensives is frequently caused by obstructive sleep apnea and/or inappropriately high plasma aldosterone levels. In other words, obese hypertensives may have sleep apnea, obese hypertensives without sleep apnea may have inappropriately elevated levels of plasma aldosterone, and a surprising number of obese patients with sleep apnea also have elevated levels of aldosterone. The mechanisms by which obesity and obstructive sleep apnea increase aldosterone levels and raise blood pressure are not understood, but sympathetic nervous system activation and production of nonclassical adrenal stimuli are two possibilities. Obstructive sleep apnea can be detected with a careful history and various sleep studies. Inappropriately elevated aldosterone levels can be detected by measuring the ratio of plasma aldosterone concentration to plasma renin activity. Successful treatment of these resistant hypertensives often can be achieved by devices that provide positive pressure to the upper airway to correct obstructive sleep apnea and by incorporating an aldosterone antagonist in the therapeutic regimen.

Key Words: obesity • aldosterone • sleep apnea • hypertension • fatty acids • renin

This article has been cited by other articles:

				S. Alvarez-Madrazo, S. Padmanabhan, B. M. Mayosi, H. Watkins, P. Avery, A. M. Wallace, R. Fraser, E. Davies, B. Keavney, and J. M. Connell Familial and Phenotypic Associations of the Aldosterone Renin Ratio J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4324 - 4333. [Abstract] [Full Text] [PDF]

				E. D. Bruder, J. K. Taylor, K. J. Kamer, and H. Raff Development of the ACTH and corticosterone response to acute hypoxia in the neonatal rat Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1195 - R1203. [Abstract] [Full Text] [PDF]

				V. K. Somers, D. P. White, R. Amin, W. T. Abraham, F. Costa, A. Culebras, S. Daniels, J. S. Floras, C. E. Hunt, L. J. Olson, et al. Sleep Apnea and Cardiovascular Disease: An American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health) Circulation, September 2, 2008; 118(10): 1080 - 1111. [Full Text] [PDF]

				J. W. Funder, R. M. Carey, C. Fardella, C. E. Gomez-Sanchez, F. Mantero, M. Stowasser, W. F. Young Jr., and V. M. Montori Case Detection, Diagnosis, and Treatment of Patients with Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3266 - 3281. [Abstract] [Full Text] [PDF]

				V. K. Somers, D. P. White, R. Amin, W. T. Abraham, F. Costa, A. Culebras, S. Daniels, J. S. Floras, C. E. Hunt, L. J. Olson, et al. Sleep Apnea and Cardiovascular Disease: An American Heart Association/American College of Cardiology Foundation Scientific Statement From the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing In Collaboration With the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health) J. Am. Coll. Cardiol., August 19, 2008; 52(8): 686 - 717. [Full Text] [PDF]

				A. W. Krug and M. Ehrhart-Bornstein Aldosterone and Metabolic Syndrome: Is Increased Aldosterone in Metabolic Syndrome Patients an Additional Risk Factor? Hypertension, May 1, 2008; 51(5): 1252 - 1258. [Full Text] [PDF]

				G. Colussi, C. Catena, R. Lapenna, E. Nadalini, A. Chiuch, and L. A. Sechi Insulin Resistance and Hyperinsulinemia Are Related to Plasma Aldosterone Levels in Hypertensive Patients Diabetes Care, September 1, 2007; 30(9): 2349 - 2354. [Abstract] [Full Text] [PDF]

				J. H. Pratt The Adrenergic Nervous System Conversing With the Adrenal Cortex: New Implications for Salt-Sensitive Hypertension Hypertension, November 1, 2006; 48(5): 820 - 821. [Full Text] [PDF]

				D. P. Papadopoulos and V. Papademetriou Resistant Hypertension: Diagnosis and Management Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2006; 11(2): 113 - 118. [Abstract] [PDF]

				D. Norman, J. S. Loredo, R. A. Nelesen, S. Ancoli-Israel, P. J. Mills, M. G. Ziegler, and J. E. Dimsdale Effects of Continuous Positive Airway Pressure Versus Supplemental Oxygen on 24-Hour Ambulatory Blood Pressure Hypertension, May 1, 2006; 47(5): 840 - 845. [Abstract] [Full Text] [PDF]

				J. M C Connell and E. Davies The new biology of aldosterone J. Endocrinol., July 1, 2005; 186(1): 1 - 20. [Abstract] [Full Text] [PDF]

				T. M. Buckley and A. F. Schatzberg On the Interactions of the Hypothalamic-Pituitary-Adrenal (HPA) Axis and Sleep: Normal HPA Axis Activity and Circadian Rhythm, Exemplary Sleep Disorders J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3106 - 3114. [Abstract] [Full Text] [PDF]

				K. Rahmouni, M. L.G. Correia, W. G. Haynes, and A. L. Mark Obesity-Associated Hypertension: New Insights Into Mechanisms Hypertension, January 1, 2005; 45(1): 9 - 14. [Abstract] [Full Text] [PDF]

				A. M. Sharma Is There a Rationale for Angiotensin Blockade in the Management of Obesity Hypertension? Hypertension, July 1, 2004; 44(1): 12 - 19. [Abstract] [Full Text] [PDF]