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Characterization of Resistant Hypertension<subtitle>Association Between Resistant Hypertension, Aldosterone, and Persistent Intravascular Volume Expansion</subtitle>
Open accessAbstract
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 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]
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“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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Chobanian, A. V. (2003) · JAMA · doi:10.1001/jama.289.19.2560 · Cited by 25,386
Chobanian, A. V., Bakris, G. L., Black, H. R., Cushman, W. C., Green, L. A., Izzo, J. L., Jones, D. W., Materson, B. J., Oparil, S., Wright, J. T., et al. (2003) · Hypertension · doi:10.1161/01.hyp.0000107251.49515.c2 · Cited by 13,271
Hajjar, I. M. (2003) · JAMA · doi:10.1001/jama.290.2.199 · Cited by 2,399
Pepine, C. J., Handberg, E. M., Cooper‐DeHoff, R. M., Marks, R. G., Kowey, P. R., Messerli, F. H., Mancia, G., Cangiano, J. L., García-Barreto, D., Keltai, M., et al. (2003) · JAMA · doi:10.1001/jama.290.21.2805 · Cited by 1,278
Cushman, W. C., Ford, C. E., Cutler, J. A., Margolis, K. L., Davis, B. R., Grimm, R. H., Black, H. R., Hamilton, B. P., Holland, J., Nwachuku, C., et al. (2002) · The Journal of Clinical Hypertension · doi:10.1111/j.1524-6175.2002.02045.x · Cited by 979
Hyperaldosteronism Among Black and White Subjects With Resistant Hypertension
Calhoun, D. A., Nishizaka, M. K., Zaman, M. A., Thakkar, R. B., & Weissmann, P. (2002) · Hypertension · doi:10.1161/01.hyp.0000040261.30455.b6 · Cited by 763
Black, H. R. (2003) · JAMA · doi:10.1001/jama.289.16.2073 · Cited by 741
Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension
Chapman, N., Dobson, J., Wilson, S. L., Dahlöf, B., Sever, P., Wedel, H., & Poulter, N. R. (2007) · Hypertension · doi:10.1161/01.hyp.0000259805.18468.8c · Cited by 630
Serum Aldosterone and the Incidence of Hypertension in Nonhypertensive Persons
Vasan, R. S., Evans, J. C., Larson, M. G., Wilson, P. W. F., Meigs, J. B., Rifai, N., Benjamin, E. J., & Levy, D. A. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa033263 · Cited by 573
Efficacy of low-dose spironolactone in subjects with resistant hypertension
Nishizaka, M. (2003) · American Journal of Hypertension · doi:10.1016/s0895-7061(03)01032-x · Cited by 500
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2013 ESH/ESC Guidelines for the management of arterial hypertension
Authors Task Force Members, Mancia, G., Fagard, R., Narkiewicz, K., Redon, J., Zanchetti, A., Böhm, M., Christiaens, T., Cífková, R., Backer, G. D., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht151 · Cited by 13,739
Mancia, G., Fagard, R., Narkiewicz, K., Redón, J., Zanchetti, A., Böhm, M., Christiaens, T., Cifkova, R., De Backer, G., Dominiczak, A., et al. (2013) · Journal of Hypertension · doi:10.1097/01.hjh.0000431740.32696.cc · Cited by 5,655
Mancia, G., Kreutz, R., Brunström, M., Burnier, M., Grassi, G., Januszewicz, A., Muiesan, M. L., Tsioufis, K., Agabiti-Rosei, E., Algharably, E. A. E., et al. (2023) · Journal of Hypertension · doi:10.1097/hjh.0000000000003480 · Cited by 3,473
2024 ESC Guidelines for the management of elevated blood pressure and hypertension
McEvoy, J. W., McCarthy, C. P., Bruno, R. M., Brouwers, S., Canavan, M. D., Ceconi, C., Christodorescu, R. M., Daskalopoulou, S. S., Ferro, C. J., Gerdts, E., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae178 · Cited by 2,298
The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019)
Umemura, S., Arima, H., Arima, S., Asayama, K., Dohi, Y., Hirooka, Y., Horio, T., Hoshide, S., Ikeda, S., Ishimitsu, T., et al. (2019) · Hypertension Research · doi:10.1038/s41440-019-0284-9 · Cited by 1,880
Metadata
- 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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