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Brief Report
August 2018

Incidence of Atrial Fibrillation and Mineralocorticoid Receptor Activity in Patients With Medically and Surgically Treated Primary Aldosteronism

Author Affiliations
  • 1Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 2Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 3Department of Epidemiology, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 4Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. 2018;3(8):768-774. doi:10.1001/jamacardio.2018.2003
Key Points

Question  Can the risk of patients with primary aldosteronism developing atrial fibrillation be lowered with mineralocorticoid receptor (MR) antagonists or surgical adrenalectomy?

Findings  In this large cohort study, patients with primary aldosteronism treated with MR antagonists had a 2.5-fold higher risk for incident atrial fibrillation when their renin remained suppressed (a marker of insufficient MR blockade) compared with matched patients with essential hypertension. In contrast, patients with primary aldosteronism whose renin substantially increased with MR antagonists and patients who underwent surgical adrenalectomy had no significant difference in incident atrial fibrillation risk compared with an age-matched cohort of patients with essential hypertension.

Meaning  Activation of the MR by aldosterone may play an important role in the development of atrial fibrillation, and adequate blockade or removal of this aldosterone may prevent incident atrial fibrillation.

Abstract

Importance  Primary aldosteronism (PA) is an ideal condition to evaluate the role of the mineralocorticoid receptor (MR) in the pathogenesis of atrial fibrillation (AF).

Objective  To investigate whether MR antagonist therapy or surgical adrenalectomy in PA influence the risk for incident AF.

Design  This cohort study included patients aged 18 years and older. Patients with PA and age-matched patients with essential hypertension were identified via electronic health records. Patients with a history of AF, myocardial infarction, congestive heart failure, or stroke were excluded. Data were collected between 1991 and the end of 2016 in an academic medical center, with a mean follow-up duration of approximately 8 years.

Exposures  Patients with PA treated with MR antagonists or surgical adrenalectomy were compared with patients with essential hypertension. Patients with PA who were treated with MR antagonists were categorized by whether their plasma renin activity remained suppressed (< 1 ng/mL/h) or substantially increased (≥ 1 ng/mL/h), as proxies for insufficient or sufficient MR blockade.

Main Outcomes and Measure  Incident AF.

Results  A total of 195 patients with PA who were treated with MR antagonists and 201 patients with PA treated with surgical adrenalectomy were included, as well as 40 092 age-matched patients with essential hypertension. Despite similar blood pressure at study entry and throughout follow-up, patients with PA who were treated with MR antagonists whose renin remained suppressed had a higher risk for incident AF than patients with essential hypertension (adjusted HR, 2.55 [95% CI, 1.75-3.71]). They also had an adjusted 10-year cumulative AF incidence difference of 14.1 (95% CI, 6.7-21.5) excess cases per 100 persons compared with patients with essential hypertension. In contrast, patients with PA who were treated with MR antagonists and whose renin increased and patients with PA who were treated with surgical adrenalectomy had no statistically significant difference in risk for incident AF compared with patients with essential hypertension.

Conclusions and Relevance  When compared with patients with essential hypertension, patients with PA treated with MR antagonists such that renin remained suppressed (as a proxy for insufficient MR blockade) had a significantly higher risk for incident AF; however, treatment of PA with MR antagonists to substantially increase renin (suggesting sufficient MR blockade), or with surgical adrenalectomy (to remove the source of aldosteronism), was associated with no significant difference in risk for developing AF. These findings add to the growing body of evidence suggesting that MR blockade may be a potential therapy to decrease the incidence of AF.

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