Prevalence of Primary Aldosteronism Across the Stages of Hypertension Based on a New Combined Overnight Test

Abstract

Primary aldosteronism (PA) is the most common endocrine cause of arterial hypertension. Despite the increasing incidence of hypertension worldwide, the true prevalence of PA in hypertension was only recently recognized. The objective of the work was to estimate the prevalence of PA in patients at different stages of hypertension based on a newly developed screening-diagnostic overnight test. This is a prospective study with hypertensive patients (n=265) at stage I (n=100), II (n=88), and III (n=77) of hypertension. A group of 103 patients with essential hypertension without PA was used as controls. PA diagnosis was based on a combined screening-diagnostic overnight test, the Dexamethasone-Captopril-Valsartan Test (DCVT) that evaluates aldosterone secretion after pharmaceutical blockade of angiotensin-II and adrenocorticotropic hormone. DCVT was performed in all participants independently of the basal aldosterone to renin ratio (ARR). The calculated upper normal limits for post-DCVT aldosterone levels [3 ng/dl (85 pmol/l)] and post-DCVT ARR [0.32 ng/dl/μU/ml (9 pmol/IU)] from controls, were applied together to establish PA diagnosis. Using these criteria PA was confirmed in 80 of 265 (30%) hypertensives. The prevalence of PA was: 21% (21/100) in stage I, 33% (29/88) in stage II, and 39% (30/77) in stage III. Serum K⁺ levels were negatively correlated and urinary K⁺ was positively correlated in PA patients with post-DCVT ARR (r=–0.349, p <0.01, and r=0.27, p <0.05 respectively). In conclusion, DCVT revealed that PA is a highly prevalent cause of hypertension. DCVT could be employed as a diagnostic tool in all subjects with arterial hypertension of unknown cause.

Key words

prevalence - primary aldosteronism - hypertension - aldosterone to renin ratio

Publication History

Received: 16 March 2021

Accepted after revision: 04 May 2021

Article published online:
19 July 2021

• References

• 1 Funder JW, Carey RM, Mantero F. et al. The management of primary aldosteronism: Case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 1889-1916
• 2 Catena C, Colussi GL, Nadalini E. et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168: 80-85
• 3 Milliez P, Girerd X, Plouin PF. et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248
• 4 Mulatero P, Monticone S, Bertello C. et al. Long-Term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab 2013; 98: 4826-4833
• 5 Savard S, Amar L, Plouin PF. et al. Cardiovascular complications associated with primary aldosteronism: A controlled cross-sectional study. Hypertension 2013; 62: 331-336
• 6 Rossi GP, Cesari M, Cuspidi C. et al. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension 2013; 62: 62-69
• 7 Rossi GP, Maiolino G, Flego A. et al. Adrenalectomy Lowers Incident Atrial Fibrillation in Primary Aldosteronism Patients at Long Term. Hypertension 2018; 71: 585-591
• 8 Chen W, Li F, He C. et al. Elevated prevalence of abnormal glucose metabolism in patients with primary aldosteronism: A meta-analysis. Ir J Med Sci 2014; 183: 283-291
• 9 Hanslik G, Wallaschofski H, Dietz A. et al. Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn’s Registry. Eur J Endocrinol 2015; 173: 665-675
• 10 Fallo F, Veglio F, Bertello C. et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab 2006; 91: 454-459
• 11 Monticone S, D’Ascenzo F, Moretti C. 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: 41-50
• 12 Vaidya A, Mulatero P, Baudrand R. et al. The Expanding Spectrum of Primary Aldosteronism: Implications for Diagnosis, Pathogenesis, and Treatment. Endocr Rev 2018; 39: 1057-1088
• 13 Conn J.. Presidential address. I. Painting background. II. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med 1955; 45: 3-17
• 14 Yang Y, Reincke M, Williams TA.. Prevalence, diagnosis and outcomes of treatment for primary aldosteronism. Best Pract Res Clin Endocrinol Metab 2020; 34: 101365
• 15 Käyser SC, Dekkers T, Groenewoud HJ. et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: A systematic review and meta-regression analysis. J Clin Endocrinol Metab 2016; 101: 2826-2835
• 16 Mosso L, Carvajal C, González A. et al. Primary aldosteronism and hypertensive disease. Hypertension 2003; 42: 161-165
• 17 Rossi GP, Bernini G, Caliumi C. et al. A Prospective Study of the Prevalence of Primary Aldosteronism in 1,125 Hypertensive Patients. J Am Coll Cardiol 2006; 48: 2293-2300
• 18 Monticone S, Burrello J, Tizzani D. et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69: 1811-1820
• 19 Xu Z, Yang J, Hu J. et al. Primary Aldosteronism in patients in china with recently detected hypertension. J Am Coll Cardiol 2020; 75: 1913-1922
• 20 Brown JM, Siddiqui M, Calhoun DA. et al. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann Intern Med 2020; 173: 10-20
• 21 Gouli A, Kaltsas G, Tzonou A. et al. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest 2011; 41: 1227-1236
• 22 Papanastasiou L, Markou A, Pappa T. et al. Primary aldosteronism in hypertensive patients: Clinical implications and target therapy. Eur J Clin Invest 2014; 44: 697-706
• 23 Tsiavos V, Markou A, Papanastasiou L. et al. A new highly sensitive and specific overnight combined screening and diagnostic test for primary aldosteronism. Eur J Endocrinol 2016; 175: 21-28
• 24 Piaditis GP, Kaltsas G, Markou A. et al. Five Reasons for the Failure to Diagnose Aldosterone Excess in Hypertension. Horm Metab Res 2020; 52: 827-833
• 25 Mancia G, Fagard R, Narkiewicz K. et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159-2219
• 26 Levey AS, Stevens LA, Schmid CH. et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-612
• 27 Piaditis G, Markou A, Papanastasiou L. et al. Progress in aldosteronism: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. Eur J Endocrinol 2015; 172: 191-203
• 28 Markou A, Sertedaki A, Kaltsas G. et al. Stress-induced aldosterone hyper-secretion in a substantial subset of patients with essential hypertension. J Clin Endocrinol Metab 2015; 100: 2857-2864
• 29 Nieman LK, Biller BMK, Findling JW. et al. The diagnosis of Cushing’s syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
• 30 Buffolo F, Monticone S, Burrello J. et al. Is primary aldosteronism still largely unrecognized?. Horm Metab Res 2017; 49: 908-914
• 31 Jaffe G, Gray Z, Krishnan G. et al. Screening rates for primary aldosteronism in resistant hypertension: a cohort study. Hypertension 2020; 75: 650-659