Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion

Abstract

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 <or=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.

Figure 1

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) values in resistant hypertensive subjects (n=279) and controls (n=53) (top panel). There was a significant incremental increase in ANP and BNP values between controls (n=53), resistant hypertensive subjects with normal -aldo (n=197) and high-aldo (n=82) (bottom panel).

Figure 2

Correlation between 24-hour urinary aldosterone (reference range 2 to 16 μg/24-hr) and urinary cortisol (reference range 56 to 286 μg /24-hr) among patients with resistant hypertension (top panel) and controls (bottom panel).