• 1.

    Vaidya A, et al.. The unrecognized prevalence of primary aldosteronism. Ann Intern Med 2020; 173:683. doi: 10.7326/L20-1097

  • 2.

    Monticone S, et al.. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69:18111820. doi: 10.1016/j.jacc.2017.01.052

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Paolo Rossi G, et al.. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48:22932300. doi: 10.1016/j.jacc.2006.07.059

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Calhoun DA, et al.. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40:892896. doi: 10.1161/01.hyp.0000040261.30455.b6

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Hundemer GL, et al.. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: A retrospective cohort study. Lancet Diabetes Endocrinol 2018; 6:5159. doi: 10.1016/S2213-8587(17)30367-4

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Byrd JB, et al.. Primary aldosteronism: Practical approach to diagnosis and management. Circulation 2018; 138:823835. doi: 10.1161/CIRCULATIONAHA.118.033597

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Funder JW, et al.. The management of primary aldosteronism: Case detection, diagnosis, and treatment: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2016; 101:18891916. doi: 10.1210/jc.2015-4061

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Whelton PK, et al.. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018; 71:12691324. doi: 10.1161/HYP.0000000000000066

    • Search Google Scholar
    • Export Citation
  • 9.

    Jaffe G, et al.. Screening rates for primary aldosteronism in resistant hypertension: A cohort study. Hypertension 2020; 75:650659. doi: 10.1161/HYPERTENSIONAHA.119.14359

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Ruhle BC, et al.. Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives. Surgery 2019; 165:221227. doi: 10.1016/j.surg.2018.05.085

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Sivarajah M, et al.. Adherence to consensus guidelines for screening of primary aldosteronism in an urban healthcare system. Surgery 2020; 167:211215. doi: 10.1016/j.surg.2019.05.087

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Cohen JB, et al.. Testing for primary aldosteronism and mineralocorticoid receptor antagonist use among U.S. veterans: A retrospective cohort study. Ann Intern Med [published online ahead of print December 29, 2020]. doi: 10.7326/M20-4873; https://www.acpjournals.org/doi/10.7326/M20-4873

    • Search Google Scholar
    • Export Citation

Don’t Forget about the Other A in the RAAS; Primary Aldosteronism Is More Common Than You Think

  • 1 James Brian Byrd, MD, MS, is Assistant Professor of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical School, Ann Arbor. Jordana B. Cohen, MD, MSCE, is Assistant Professor of Medicine and Epidemiology, Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Full access

Recent data demonstrate that primary aldosteronism is much more common than previously believed (1). Despite common perceptions among many providers, most patients with primary aldosteronism do not have hypokalemia (2, 3). Importantly, patients with treatment-resistant hypertension have a particularly high prevalence of primary aldosteronism (∼20%) (1, 4). Primary aldosteronism is associated with increased risk of development and progression of chronic kidney disease, heart disease, and mortality (5). Nonetheless, primary aldosteronism responds to treatment with a mineralocorticoid receptor antagonist and is curable with adrenalectomy in some patients (i.e., those

Recent data demonstrate that primary aldosteronism is much more common than previously believed (1). Despite common perceptions among many providers, most patients with primary aldosteronism do not have hypokalemia (2, 3). Importantly, patients with treatment-resistant hypertension have a particularly high prevalence of primary aldosteronism (∼20%) (1, 4). Primary aldosteronism is associated with increased risk of development and progression of chronic kidney disease, heart disease, and mortality (5). Nonetheless, primary aldosteronism responds to treatment with a mineralocorticoid receptor antagonist and is curable with adrenalectomy in some patients (i.e., those with an aldosterone-secreting adrenal adenoma or who lateralize on adrenal vein sampling) (6).

Accordingly, clinical guidelines (7, 8) recommend testing for primary aldosteronism in patients with treatment-resistant hypertension. However, recent studies from local health systems suggest that <3% of individuals who meet guideline criteria are screened for primary aldosteronism (9−11). Similarly, clinical experience suggests that many overt cases of primary aldosteronism—with all the classical features and resulting cardiometabolic complications—go undiagnosed and without proper treatment for years (6).

In a national cohort of 269,010 veterans with new-onset, apparent treatment-resistant hypertension (i.e., elevated blood pressure on at least three antihypertensive agents or controlled blood pressure requiring at least four antihypertensive agents) from 2000 to 2017, we found that just 1.6% of veterans underwent testing for primary aldosteronism (with concomitant measurement of plasma aldosterone and renin on or after meeting criteria for resistant hypertension) (12) (Visual Abstract). Patients whose initial visit was with a nephrologist or an endocrinologist were about twice as likely to undergo testing as those seen by a primary care provider or cardiologist. Testing for primary aldosteronism, regardless of the results of testing, was associated with a fourfold higher likelihood of receiving a mineralocorticoid receptor antagonist compared with no testing. This observation argues against the possibility that clinicians usually bypass testing and simply prescribe a mineralocorticoid receptor antagonist for patients with resistant hypertension. In addition, we observed that blood pressure was better controlled over time in patients who underwent testing.

Our work is consistent with prior studies demonstrating low rates of testing for primary aldosteronism in smaller, local health systems (9). Together, the studies show a lack of appropriate testing for primary aldosteronism, which is currently neglected relative to its impact on patients.

Overall, we observed ample missed opportunities for appropriate testing and treatment of patients with resistant hypertension. Our findings suggests that there are critical gaps in provider knowledge of the importance of screening patients with resistant hypertension for primary aldosteronism and that there are likely barriers to implementing appropriate antihypertensive management in these patients.

Visual Abstract by Sophia L. Ambruso

Conflicts of interest: Dr. Byrd holds an NIH grant investigating novel approaches to diagnosing excess mineralocorticoid receptor activation and is an inventor on a provisional patent for a novel diagnostic test related to primary aldosteronism. He has served on an advisory board for Phase Bio, which is developing an aldosterone synthase inhibitor. Dr. Cohen holds NIH grants investigating optimization of antihypertensive management in high-risk patient populations.

References

  • 1.

    Vaidya A, et al.. The unrecognized prevalence of primary aldosteronism. Ann Intern Med 2020; 173:683. doi: 10.7326/L20-1097

  • 2.

    Monticone S, et al.. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69:18111820. doi: 10.1016/j.jacc.2017.01.052

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Paolo Rossi G, et al.. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48:22932300. doi: 10.1016/j.jacc.2006.07.059

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Calhoun DA, et al.. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40:892896. doi: 10.1161/01.hyp.0000040261.30455.b6

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Hundemer GL, et al.. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: A retrospective cohort study. Lancet Diabetes Endocrinol 2018; 6:5159. doi: 10.1016/S2213-8587(17)30367-4

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Byrd JB, et al.. Primary aldosteronism: Practical approach to diagnosis and management. Circulation 2018; 138:823835. doi: 10.1161/CIRCULATIONAHA.118.033597

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Funder JW, et al.. The management of primary aldosteronism: Case detection, diagnosis, and treatment: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2016; 101:18891916. doi: 10.1210/jc.2015-4061

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Whelton PK, et al.. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018; 71:12691324. doi: 10.1161/HYP.0000000000000066

    • Search Google Scholar
    • Export Citation
  • 9.

    Jaffe G, et al.. Screening rates for primary aldosteronism in resistant hypertension: A cohort study. Hypertension 2020; 75:650659. doi: 10.1161/HYPERTENSIONAHA.119.14359

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Ruhle BC, et al.. Keeping primary aldosteronism in mind: Deficiencies in screening at-risk hypertensives. Surgery 2019; 165:221227. doi: 10.1016/j.surg.2018.05.085

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Sivarajah M, et al.. Adherence to consensus guidelines for screening of primary aldosteronism in an urban healthcare system. Surgery 2020; 167:211215. doi: 10.1016/j.surg.2019.05.087

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Cohen JB, et al.. Testing for primary aldosteronism and mineralocorticoid receptor antagonist use among U.S. veterans: A retrospective cohort study. Ann Intern Med [published online ahead of print December 29, 2020]. doi: 10.7326/M20-4873; https://www.acpjournals.org/doi/10.7326/M20-4873

    • Search Google Scholar
    • Export Citation
Save