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Association Between Resistant Hypertension, Aldosterone, and Persistent Intravascular Volume Expansion

Krishna K. Gaddam, MD; Mari K. Nishizaka, MD; Monique N. Pratt-Ubunama, MD; Eduardo Pimenta, MD; Inmaculada Aban, PhD; Suzanne Oparil, MD; David A. Calhoun, MD

Arch Intern Med. 2008;168(11):1159-1164.

Background  Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage.

Methods  We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using 2 antihypertensive medications). Participants were prospectively examined for plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, brain-type natriuretic peptide, atrial natriuretic peptide, and 24-hour urinary aldosterone (UAldo), cortisol, sodium, and potassium values while adhering to a routine diet.

Results  Plasma aldosterone (P < .001), aldosterone to renin ratio (P < .001), 24-hour UAldo (P = .02), brain-type natriuretic peptide (P = .007), and atrial natriuretic peptide (P = .001) values were higher and plasma renin activity (P = .02) and serum potassium (P < .001) values were lower in patients with resistant hypertension vs controls. Of patients with resistant hypertension, men had significantly higher plasma aldosterone (P = .003), aldosterone to renin ratio (P = .02), 24-hour UAldo (P < .001), and urinary cortisol (P < .001) values than women. In univariate linear regression analysis, body mass index (P = .01), serum potassium (P < .001), urinary cortisol (P < .001), urinary sodium (P = .02), and urinary potassium (P < .001) values were correlated with 24-hour UAldo levels. Serum potassium (P = .001), urinary potassium (P < .001), and urinary sodium (P = .03) levels were predictors of 24-hour UAldo levels in multivariate modeling.

Conclusions  Aldosterone levels are higher and there is evidence of intravascular volume expansion (higher brain-type and atrial natriuretic peptide levels) in patients with resistant hypertension vs controls. These differences are most pronounced in men. A significant correlation between 24-hour urinary aldosterone levels and cortisol excretion suggests that a common stimulus, such as corticotropin, may underlie the aldosterone excess in patients with resistant hypertension.

Author Affiliations: Vascular Biology and Hypertension Program (Drs Gaddam, Nishizaka, Pratt-Ubunama, Pimenta, Oparil, and Calhoun) and Department of Biostatistics, School of Public Health (Dr Aban), University of Alabama at Birmingham.

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