Primary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment
Purpose of Review
Primary aldosteronism (PA) is a common form of hypertension characterized by autonomous aldosterone secretion from one or both adrenal glands. The purpose of this review is to synthesize recent research findings regarding cardiovascular disease risk in PA both pre- and post-targeted therapy.
Previously considered a rare disease, recent prevalence studies demonstrate that PA is actually a very common, yet vastly under-diagnosed, etiology of hypertension. Prior to targeted therapy, PA is associated with substantially higher rates of cardiovascular disease compared with essential hypertension. Surgical adrenalectomy is highly effective in curing or improving hypertension as well as mitigating cardiovascular disease risk in patients with unilateral PA. For the remainder of PA patients, MR antagonists are recommended; however, several recent studies have brought into question their effectiveness in improving cardiovascular outcomes.
PA is a common cause of hypertension that leads to disproportionately high rates of cardiovascular disease. Future studies are needed to enhance the clinical approach to both identification and treatment of patients with PA to optimize long-term cardiovascular outcomes.
KeywordsPrimary aldosteronism Primary hyperaldosteronism Conn’s syndrome Mineralocorticoid receptor antagonist Cardiovascular disease Atrial fibrillation
Compliance with Ethical Standards
Conflict of Interest
Gregory L. Hundemer declares that he has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 15.•• Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69(14):1811–20 Large well-designed study assessing the prevalence of primary aldosteronism in the hypertensive population.PubMedGoogle Scholar
- 24.•• Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(5):1889–916 Most widely accepted guidelines for the evaluation and management of primary aldosteronism.PubMedGoogle Scholar
- 30.Young WF. Primary aldosteronism: renaissance of a syndrome. Clin Endocrinol. 2007;66(5):607–18.Google Scholar
- 35.Nanba AT, Nanba K, Byrd JB, Shields JJ, Giordano TJ, Miller BS, et al. Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism. Clin Endocrinol. 2017;87(6):665–72.Google Scholar
- 36.•• Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017;5(9):689–99 Large international study assessing outcomes in unilateral primary aldosteronism following surgical adrenalectomy.PubMedPubMedCentralGoogle Scholar
- 44.Cesari M, Letizia C, Angeli P, Sciomer S, Rosi S, Rossi GP. Cardiac remodeling in patients with primary and secondary aldosteronism: a tissue Doppler study. Circ Cardiovasc Imaging. 2016;9(6).Google Scholar
- 52.•• Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018;6(1):51–9 Large retrospective study comparing cardiovascular outcomes in primary aldosteronism post-targeted therapy (surgical adrenalectomy or mineralocorticoid receptor antagonists) versus comparable patients with essential hypertension. Additionally, this study suggests that renin may be an informative biomarker to guide treatment in primary aldosteronism.PubMedGoogle Scholar
- 54.•• Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018;6(1):41–50 Recent meta-analysis on cardiovascular outcomes in primary aldosteronism prior to targeted therapy versus essential hypertension.PubMedGoogle Scholar
- 56.Takeda R, Matsubara T, Miyamori I, Hatakeyama H, Morise T. Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension. The Research Committee of Disorders of Adrenal Hormones in Japan. J Endocrinol Investig. 1995;18(5):370–3.Google Scholar
- 59.Swedberg K, Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Shi H, et al. Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) study. J Am Coll Cardiol. 2012;59(18):1598–603.PubMedGoogle Scholar
- 60.• Takemoto Y, Ramirez RJ, Kaur K, Salvador-Montanes O, Ponce-Balbuena D, Ramos-Mondragon R, et al. Eplerenone reduces atrial fibrillation burden without preventing atrial electrical remodeling. J Am Coll Cardiol. 2017;70(23):2893–905 Animal model demonstrating that blockade of the mineralocorticoid receptor can prevent atrial fibrillation.PubMedPubMedCentralGoogle Scholar
- 64.•• Rossi GP, Maiolino G, Flego A, Belfiore A, Bernini G, Fabris B, et al. Adrenalectomy lowers incident atrial fibrillation in primary aldosteronism patients at long term. Hypertension. 2018;71(4):585–91 Observational study showing that surgical adrenalectomy in primary aldosteronism is effective at reducing incident atrial fibrillation whereas patients treated with mineralocorticoid receptor antagonists remain at higher risk.PubMedGoogle Scholar
- 65.•• Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Incidence of atrial fibrillation and mineralocorticoid receptor activity in patients with medically and surgically treated primary aldosteronism. JAMA Cardiol. 2018;3(8):768–74 Observational study showing that greater mineralocorticoid receptor blockade, as reflected by a rise in renin, associates with a lower risk of incident atrial fibrillation.PubMedPubMedCentralGoogle Scholar
- 80.• Arlt W, Lang K, Sitch AJ, Dietz AS, Rhayem Y, Bancos I, et al. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. 2017;2(8). Metabolomic study showing that cortisol co-secretion is common in primary aldosteronism which may explain the high co-occurrence of diabetes mellitus. Google Scholar
- 83.Duncan JL, 3rd, Fuhrman GM, Bolton JS, Bowen JD, Richardson WS. Laparoscopic adrenalectomy is superior to an open approach to treat primary hyperaldosteronism. Am Surg 2000;66(10):932–935; discussion 5-6.Google Scholar
- 92.Burrello J, Burrello A, Stowasser M, Nishikawa T, Quinkler M, Prejbisz A, et al. The primary aldosteronism surgical outcome score for the prediction of clinical outcomes after adrenalectomy for unilateral primary aldosteronism. Ann Surg. 2019.Google Scholar
- 96.Parthasarathy HK, Menard J, White WB, Young WF Jr, Williams GH, Williams B, et al. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism. J Hypertens. 2011;29(5):980–90.PubMedGoogle Scholar