Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion.
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.
Gaddam
Krishna K
KK
Vascular Biology and Hypertension Program, University of Alabama at Birmingham, 933 19th St S, Community Health Services Bldg 115, Birmingham, AL 35294, USA. drgaddam@uab.edu
Nishizaka
Mari K
MK
Pratt-Ubunama
Monique N
MN
Pimenta
Eduardo
E
Aban
Inmaculada
I
Oparil
Suzanne
S
Calhoun
David A
DA
D000450:Aldosterone / Q000378:metabolism*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D016022:Case-Control Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011188:Potassium / Q000652:urine; D012044:Regression Analysis; D012083:Renin / Q000097:blood; D012737:Sex Factors; D012964:Sodium / Q000652:urine
D000959:Antihypertensive Agents; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D011188:Potassium; D006854:Hydrocortisone