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.
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
Krishna K
KK
Gaddam
Mari K
MK
Nishizaka
Monique N
MN
Pratt-Ubunama
Eduardo
E
Pimenta
Inmaculada
I
Aban
Suzanne
S
Oparil
David A
DA
Calhoun
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