Published Online
on January 19, 2004

A more recent version of this article appeared on March 1, 2004

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Submitted on October 7, 2003
Revised on October 27, 2003

Resistant Hypertension, Obesity, Sleep Apnea, and Aldosterone. Theory and Therapy

Theodore L. Goodfriend^* and David A. Calhoun

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.

^* To whom correspondence should be addressed. E-mail: tgoodfri{at}facstaff.wisc.edu.

Abstract--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

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