Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study
Open accessAbstract
Background Mineralocorticoid receptor antagonists (MRAs) are the recommended medical therapy for primary aldosteronism (PA). Whether this recommendation effectively reduces cardiovascular risk is not well understood. Methods We conducted a cohort study including 602 PA patients treated with MRAs and 41853 age-matched patients with essential hypertension (EH) to investigate the risk for incident cardiovascular events (composite of myocardial infarction, heart failure hospitalization, stroke), atrial fibrillation, diabetes, and death in patients with PA compared with EH. Findings Both groups had comparable cardiovascular risk profiles and blood pressures throughout the study. The incidence rate of cardiovascular events was higher among PA patients on MRAs compared with EH: 56·3 (48·8, 64·7) versus 26·6 (26·1, 27·2) events per 1,000 person-years (adjusted HR=1·91 [1·63, 2·25]; adjusted 10-year cumulative incidence difference: 14·1 [10·1, 18·0] excess events per 100 persons). PA patients also had higher adjusted risks for incident mortality (HR=1·34 [1·06, 1·71]), diabetes (HR=1·26 [1·01, 1·57]), and atrial fibrillation (HR=1·93 [1·54, 2·42]). Compared with EH, the excess risk for cardiovascular events and mortality was limited to PA patients whose renin activity remained suppressed (<1 µg/L/h) on MRAs (adjusted HR=2·83 [2·11, 3·80] and 1·79 [1·14, 2·80] respectively) whereas patients who were treated with higher MRA doses and had unsuppressed renin (≥1 µg/L/h) had no significant excess risk. Interpretation Current practice of MRA therapy in PA is associated with significantly higher risk for incident cardiometabolic events and death independent of blood pressure control. Targeting MRA therapy to raise renin may mitigate this excess risk. Funding National Institutes of Health
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Primary aldosteronism is linked to impaired glucose tolerance and a higher risk of type 2 diabetes.
“Primary aldosteronism is also associated with glucose intolerance and an increased risk of type 2 diabetes (2–4)”
From Primary aldosteronism decreases insulin secretion and increases insulin clearance in humans (2020) · cites this paper as [2]
The Results section (page not available in our copy) reports a significantly higher risk of incident diabetes in patients with primary aldosteronism treated with mineralocorticoid receptor antagonists than in patients with essential hypertension. It does not report impaired glucose tolerance or specify that the incident diabetes was type 2. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPA is associated with increased risk of stroke, coronary artery disease, atrial fibrillation, heart failure, and mortality compared with matched essential hypertension.
“PA is associated with an increased risk of stroke (odds ratio [OR] 2.58, 95% CI 1.93-3.45), coronary artery disease (1.77, 1.10-2.83), atrial fibrillation (3.52, 2.06-5.99), heart failure (2.05, 1.11-3.78), and mortality (hazard ratio [HR] 1.34, 95% CI 1.06-1.71) compared with matched populations with essential hypertension (278,279).”
From Adrenal incidentaloma (2020) · cites this paper as [279]
Diabetes/metabolic syndrome, renal damage, impaired bone mineral density, and osteoporosis have been reported more prevalent in AI patients with PA.
“Diabetes mellitus/metabolic syndrome (278,279), renal damage (280), impaired bone mineral density (81), and osteoporosis (264,281,282) have also been reported to be more prevalent in AI patients with PA.”
From Adrenal incidentaloma (2020) · cites this paper as [279]
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Cites
Funder, J. W., Carey, R. M., Mantero, F., Murad, M. H., Reincke, M., Shibata, H., Stowasser, M., & Young, W. F. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-4061 · Cited by 2,925 · see citing works
The Analysis of Failure Times in the Presence of Competing Risks
Prentice, R. L., Kalbfleisch, J. D., Peterson, A. V., Flournoy, N., Farewell, V. T., & Breslow, N. E. (1978) · Biometrics · doi:10.2307/2530374 · Cited by 1,544 · see citing works
Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism
Milliez, P., Girerd, X. J., Plouin, P., Blacher, J., Safar, M. E., & Mourad, J. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.01.015 · Cited by 1,541 · see citing works
Williams, T. A., Lenders, J. W. M., Mulatero, P., Burrello, J., Rottenkolber, M., Adolf, C., Satoh, F., Amar, L., Quinkler, M. O., Deinum, J., et al. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30135-3 · Cited by 977 · see citing works
Incidence and Prognosis of Resistant Hypertension in Hypertensive Patients
Daugherty, S. L., Powers, J. D., Magid, D. J., Tavel, H. M., Masoudi, F. A., Margolis, K. L., O'Connor, P. J., Selby, J. V., & Ho, P. M. (2012) · Circulation · doi:10.1161/circulationaha.111.068064 · Cited by 930 · see citing works
Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice
Monticone, S., Burrello, J., Tizzani, D., Bertello, C., Viola, A., Buffolo, F., Gabetti, L., Mengozzi, G., Williams, T. A., Rabbia, F., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.01.052 · Cited by 888 · see citing works
Aldosterone in Congestive Heart Failure
Weber, K. T. (2001) · New England Journal of Medicine · doi:10.1056/nejmra000050 · Cited by 767 · see citing works
Cardiovascular Outcomes in Patients With Primary Aldosteronism After Treatment
Catena, C. (2008) · Archives of Internal Medicine · doi:10.1001/archinternmed.2007.33 · Cited by 566 · see citing works
Long-Term Cardio- and Cerebrovascular Events in Patients With Primary Aldosteronism
Mulatero, P., Monticone, S., Bertello, C., Viola, A., Tizzani, D., Iannaccone, A., Crudo, V. L., Burrello, J., Milan, A., Rabbia, F., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2805 · Cited by 413 · see citing works
Long-term Renal Outcomes in Patients With Primary Aldosteronism
Sechi, L. A., Novello, M., Lapenna, R., Baroselli, S., Nadalini, E., Colussi, G., & Catena, C. (2006) · JAMA · doi:10.1001/jama.295.22.2638 · Cited by 389 · see citing works
Prevalence and Characteristics of the Metabolic Syndrome in Primary Aldosteronism
Fallo, F., Veglio, F., Bertello, C., Sonino, N., Della Mea, P., Ermani, M., Rabbia, F., Federspil, G., & Mulatero, P. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1733 · Cited by 372 · see citing works
Catena, C., Colussi, G., Lapenna, R., Nadalini, E., Chiuch, A., Gianfagna, P., & Sechi, L. A. (2007) · Hypertension · doi:10.1161/hypertensionaha.107.095448 · Cited by 359 · see citing works
Rossi, G. P., Cesari, M., Cuspidi, C., Maiolino, G., Cicala, M. V., Bisogni, V., Mantero, F., & Pessina, A. C. (2013) · Hypertension · doi:10.1161/hypertensionaha.113.01316 · Cited by 354 · see citing works
Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors
McCurley, A., Pires, P. W., Bender, S. B., Aronovitz, M. A., Zhao, M. J., METZGER, D., Chambon, P., Hill, M. A., Dorrance, A. M., Mendelsohn, M. E., et al. (2012) · Nature Medicine · doi:10.1038/nm.2891 · Cited by 349 · see citing works
Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism
Arlt, W., Lang, K., Sitch, A. J., Dietz, A. S., Rhayem, Y., Bancos, I., Feuchtinger, A., Chortis, V., Gilligan, L. C., Ludwig, P., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.93136 · Cited by 281 · see citing works
Observational Study Mortality in Treated Primary Aldosteronism
Reincke, M., Fischer, E., Gerum, S., Merkle, K., Schulz, S., Pallauf, A., Quinkler, M. O., Hanslik, G., Lang, K., Hahner, S., et al. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.197111 · Cited by 279 · see citing works
The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A Cohort Study
Brown, J. M., Robinson-Cohen, C., Luque-Fernandez, M. A., Allison, M. A., Baudrand, R., Ix, J. H., Kestenbaum, B., de Boer, I. H., & Vaidya, A. (2017) · Annals of Internal Medicine · doi:10.7326/m17-0882 · Cited by 221 · see citing works
Self-citationContinuum of Renin-Independent Aldosteronism in Normotension
Baudrand, R. F., Guarda, F. J., Fardella, C., Hundemer, G. L., Brown, J. M., Williams, G. H., & Vaidya, A. (2017) · Hypertension · doi:10.1161/hypertensionaha.116.08952 · Cited by 205 · see citing works
Self-citationEndothelial Mineralocorticoid Receptor Mediates Diet-Induced Aortic Stiffness in Females
Jia, G., Habibi, J., Aroor, A. R., Martinez‐Lemus, L. A., DeMarco, V. G., Ramirez‐Perez, F. I., Sun, Z., Hayden, M. R., Meininger, G. A., Mueller, K. B., et al. (2016) · Circulation Research · doi:10.1161/circresaha.115.308269 · Cited by 172 · see citing works
Conn, J. W. (1964) · PubMed · Cited by 171 · see citing works
“Nonfunctional” Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes
Lopez, D., Luque-Fernández, M. Á., Steele, A. E., Adler, G. K., Turchin, A., & Vaidya, A. (2016) · Annals of Internal Medicine · doi:10.7326/m16-0547 · Cited by 147 · see citing works
Self-citationPlasma Renin Activity in Primary Aldosteronism
Conn, J. W. (1964) · JAMA · doi:10.1001/jama.1964.03070160046009 · Cited by 122 · see citing works
Markou, A., Pappa, T., Kaltsas, G., Gouli, A., Mitsakis, K., Tsounas, P., Prevoli, A., Tsiavos, V., Papanastasiou, L., Zografos, G., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3353 · Cited by 112 · see citing works
Risk of new-onset diabetes mellitus in primary aldosteronism
Wu, V., Chueh, S., Chen, L., Chang, C., Hu, Y., Lin, Y., Wu, K., & Yang, W. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001361 · Cited by 106 · see citing works
Piaditis, G. P., Markou, Α., Papanastasiou, L., Androulakis, I. I., & Kaltsas, G. (2014) · European Journal of Endocrinology · doi:10.1530/eje-14-0537 · Cited by 101 · see citing works
Adrenalectomy Improves Arterial Stiffness in Primary Aldosteronism
Štrauch, B., Petrák, O., Zelinka, T., et al. (2008) · American Journal of Hypertension · doi:10.1038/ajh.2008.243 · Cited by 97 · see citing works
Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism
Baudrand, R. F., Guarda, F. J., Torrey, J., Williams, G. H., & Vaidya, A. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1963 · Cited by 78 · see citing works
Self-citationArterial Hypertension, Atrial Fibrillation, and Hyperaldosteronism
Seccia, T. M., Caroccia, B., Adler, G. K., Maiolino, G., Cesari, M., & Rossi, G. P. (2017) · Hypertension · doi:10.1161/hypertensionaha.116.08956 · Cited by 67 · see citing works
Systolic Blood Pressure Levels Among Adults With Hypertension and Incident Cardiovascular Events
Rodríguez, C. J., Swett, K. R., Agarwal, S. K., Folsom, A. R., Fox, E. R., Loehr, L. R., Ni, H., Rosamond, W. D., & Chang, P. P. (2014) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2014.2482 · Cited by 59 · see citing works
Rossi, G. P., Seccia, T. M., Gallina, V., Muiesan, M. L., Leoni, L., Pengo, M. F., Ragazzo, F., Caielli, P., Belfiore, A., BERNINI, G. P., et al. (2012) · Journal of Human Hypertension · doi:10.1038/jhh.2012.21 · Cited by 29 · see citing works
An Individualized Approach to The Evaluation and Management of Primary Aldosteronism
Vaidya, A., Malchoff, C. D., & Auchus, R. J. (2017) · Endocrine Practice · doi:10.4158/ep161717.ra · Cited by 20 · see citing works
Self-citation
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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 · see citing works
Sherlock, M., Scarsbrook, A., Abbas, A., Fraser, S., Limumpornpetch, P., Dineen, R., & Stewart, P. M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa008 · Cited by 347 · see citing works
“Diabetes mellitus/metabolic syndrome (278,279), renal damage (280), impaired bone mineral density (81), and osteoporosis (264,281,282) have also been reported to be more prevalent in AI patients with PA. Clinical guidelines recommend screening for PA in every (AI) patient with hypertension or…”
BackgroundInfluentialFinerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes
Filippatos, G., Anker, S. D., Agarwal, R., Pitt, B., Ruilope, L. M., Rossing, P., Kolkhof, P., Schloemer, P., Tornus, I., Joseph, A., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.051898 · Cited by 294 · see citing works
Jones, D. W., Ferdinand, K. C., Taler, S. J., Johnson, H. M., Shimbo, D., Abdalla, M., Altieri, M. M., Bansal, N., Bello, N. A., Bress, A. P., et al. (2025) · JACC · doi:10.1016/j.jacc.2025.05.007 · Cited by 280 · see citing works
Leung, A. A., Symonds, C. J., Hundemer, G. L., Ronksley, P. E., Lorenzetti, D. L., Pasieka, J. L., Harvey, A., & Kline, G. A. (2022) · Hypertension · doi:10.1161/hypertensionaha.122.19377 · Cited by 89 · see citing works
Self-citationPrimary aldosteronism decreases insulin secretion and increases insulin clearance in humans
Adler, G. K., Murray, G. R., Turcu, A. F., Nian, H., Yu, C., Solorzano, C. C., Manning, R., Peng, D., & Luther, J. M. (2020) · Hypertension · doi:10.1161/hypertensionaha.119.13922 · Cited by 71 · see citing works
O’Shea, P. M., O’Donoghue, D., Bashari, W., Senanayake, R., Joyce, M. B., Powlson, A. S., Browne, D., O’Sullivan, G. J., Cheow, H., Mendichovszky, I., et al. (2019) · Clinical Endocrinology · doi:10.1111/cen.13942 · Cited by 58 · see citing works
Samnani, S., Cenzer, I., Kline, G. A., Lee, S. J., Hundemer, G. L., McClurg, C., Pasieka, J. L., Boscardin, W. J., Ronksley, P. E., & Leung, A. A. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad654 · Cited by 50 · see citing works
Self-citationPrimary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment
Hundemer, G. L. (2019) · Current Cardiology Reports · doi:10.1007/s11886-019-1185-x · Cited by 27 · see citing works
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- Authors
- Hundemer, G. L., Curhan, G. C., Yozamp, N., Wang, M., & Vaidya, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Vaidya, Anand
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 6
- Issue
- 1
- Pages
- 51-59
- ISSN
- 2213-8587 (ISSN-L)
- PMC
- PMC5953512
- OpenAlex
- W2767799851
- Semantic Scholar
- 727badd7834e33c6eda5d73d982e56da0ef2db3d
- Cited by
- 677
- References
- 31
- Citations by year
- 2026: 82 · 2025: 91 · 2024: 81 · 2023: 101 · 2022: 93 · 2021: 65 · 2020: 78 · 2019: 55 · 2018: 29 · 2017: 2
- FWCI
- 35.29
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Doris Duke Charitable Foundation (2015085)
- National Heart, Lung, and Blood Institute (K23HL111771)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007527, K24DK091417, R01DK107407, F32DK114953)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- primary aldosteronism, mineralocorticoid receptor antagonists, cardiovascular events, mortality, essential hypertension, cardiometabolic risk, myocardial infarction, congestive heart failure, stroke, atrial fibrillation, diabetes mellitus, comparative effectiveness, cardiovascular risk stratification, risk reclassification, shared decision-making
- MeSH terms
- Mineralocorticoid Receptor Antagonists, Cardiovascular Diseases, Female, Humans, Hyperaldosteronism, Male, Metabolic Diseases, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Incidence
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