Characterization of Resistant Hypertension<subtitle>Association Between Resistant Hypertension, Aldosterone, and Persistent Intravascular Volume Expansion</subtitle>
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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.
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Among 279 patients with resistant hypertension, brain natriuretic peptide was higher and plasma renin activity was lower than in control patients, supporting a component of relative volume excess, although 24-hour urinary sodium levels were not increased.
“Among 279 patients with RH, brain natriuretic peptide was higher and PRA was lower than in control patients, supporting a component of relative volume excess (although 24-hour urinary sodium levels were not increased).159”
From Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association (2018) · cites this paper as [159]
Among patients with resistant hypertension (n = 279, 52% women) and normotensive controls (n = 53, 45% women), women exhibited significantly lower plasma and urinary aldosterone levels than men.
“among patients with resistant hypertension (n = 279, 52% women) and normotensive controls (n = 53, 45% women), women exhibited significantly lower plasma and urinary aldosterone levels than men [ 122 ].”
From Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications (2026) · cites this paper as [122]
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- Authors
- Gaddam, K. K.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Gaddam, Krishna K.
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2008-06-09
- Volume
- 168
- Issue
- 11
- Pages
- 1159
- ISSN
- 0003-9926 (ISSN-L)
- PMC
- PMC2748247
- OpenAlex
- W2118344567
- Cited by
- 301
- References
- 32
- Citations by year
- 2026: 16 · 2025: 10 · 2024: 9 · 2023: 18 · 2022: 12 · 2021: 10 · 2020: 13 · 2019: 13 · 2018: 19 · 2017: 21 · 2016: 20 · 2015: 19 · 2014: 21 · 2013: 24 · 2012: 22
- FWCI
- 13.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-007457, HL077100, HL-075614, R01HL075614, P50HL077100, T32HL007457)
- National Center for Research Resources (M01RR00032, M01RR000032)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- resistant hypertension, plasma aldosterone, aldosterone-renin ratio, plasma renin activity, brain natriuretic peptide, atrial natriuretic peptide, intravascular volume expansion, urinary cortisol, serum potassium, urinary sodium, sex differences, body mass index, target organ damage, aldosterone excess
- MeSH terms
- Aldosterone, Antihypertensive Agents, Drug Resistance, Female, Humans, Hydrocortisone, Hypertension, Male, Middle Aged, Atrial Natriuretic Factor, Potassium, Regression Analysis, Renin, Sex Factors, Sodium, Case-Control Studies, Natriuretic Peptide, Brain
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