Causes, Evaluation, and Treatment of Secondary and Resistant Hypertension
By:
Gregory L. Hundemer Division of Nephrology, Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada

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  • 1

    Whelton PK, Carey RM, Aronow WS, Casey Jr DE, Collins KJ, Dennison Himmelfarb C, 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: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension 71: e13e115, 2018

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  • 2

    Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, et al.; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council: Resistant hypertension: Detection, evaluation, and management: A scientific statement from the American Heart Association. Hypertension 72: e53e90, 2018 PubMed

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  • 3

    Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, et al.: The spectrum of subclinical primary aldosteronism and incident hypertension: A cohort study. Ann Intern Med 167: 630641, 2017 PubMed

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  • 4

    Brown JM, Siddiqui M, Calhoun DA, Carey RM, Hopkins PN, Williams GH, et al.: The unrecognized prevalence of primary aldosteronism: A cross-sectional study. Ann Intern Med 173: 1020, 2020 PubMed

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  • 5

    Joseph JJ, Pohlman NK, Zhao S, Kline D, Brock G, Echouffo-Tcheugui JB, et al.: Association of serum aldosterone and plasma renin activity with ambulatory blood pressure in African Americans: The Jackson heart study. Circulation 143: 23552366, 2021 PubMed

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  • 6

    Carey RM, Sakhuja S, Calhoun DA, Whelton PK, Muntner P: Prevalence of apparent treatment-resistant hypertension in the United States. Hypertension 73: 424431, 2019 PubMed

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  • 7

    Tanner RM, Calhoun DA, Bell EK, Bowling CB, Gutiérrez OM, Irvin MR, et al.: Prevalence of apparent treatment-resistant hypertension among individuals with CKD. Clin J Am Soc Nephrol 8: 15831590, 2013 PubMed

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  • 8

    Sim JJ, Bhandari SK, Shi J, Reynolds K, Calhoun DA, Kalantar-Zadeh K, et al.: Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and nonresistant hypertension. Kidney Int 88: 622632, 2015 PubMed

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  • 9

    Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, et al.; CRIC Study Investigators: Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: Report from the chronic renal insufficiency cohort study. Hypertension 67: 387396, 2016 PubMed

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  • 10

    Bhatt H, Siddiqui M, Judd E, Oparil S, Calhoun D: Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement. J Am Soc Hypertens 10: 493499, 2016 PubMed

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  • 11

    Ruzicka M, Leenen FHH, Ramsay T, Bugeja A, Edwards C, McCormick B, et al.: Use of directly observed therapy to assess treatment adherence in patients with apparent treatment-resistant hypertension. JAMA Intern Med 179: 14331434, 2019 PubMed

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  • 12

    Egan BM, Zhao Y, Li J, Brzezinski WA, Todoran TM, Brook RD, et al.: Prevalence of optimal treatment regimens in patients with apparent treatment-resistant hypertension based on office blood pressure in a community-based practice network. Hypertension 62: 691697, 2013 PubMed

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  • 13

    Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC: Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation 124: 10461058, 2011 PubMed

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  • 14

    McMahon EJ, Bauer JD, Hawley CM, Isbel NM, Stowasser M, Johnson DW, et al.: A randomized trial of dietary sodium restriction in CKD. J Am Soc Nephrol 24: 20962103, 2013 PubMed

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  • 15

    Roerecke M, Kaczorowski J, Tobe SW, Gmel G, Hasan OSM, Rehm J: The effect of a reduction in alcohol consumption on blood pressure: A systematic review and meta-analysis. Lancet Public Health 2: e108e120, 2017 PubMed

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  • 16

    Lopes S, Mesquita-Bastos J, Garcia C, Bertoquini S, Ribau V, Teixeira M, et al.: Effect of exercise training on ambulatory blood pressure among patients with resistant hypertension: A randomized clinical trial. JAMA Cardiol 6: 13171323, 2021 PubMed

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  • 17

    De la Sierra A, Banegas JR, Oliveras A, Gorostidi M, Segura J, de la Cruz JJ, et al.: Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs. J Hypertens 30: 12111216, 2012 PubMed

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  • 18

    De la Sierra A, Segura J, Banegas JR, Gorostidi M, de la Cruz JJ, Armario P, et al.: Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension 57: 898902, 2011 PubMed

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  • 19

    Cohen JB, Lotito MJ, Trivedi UK, Denker MG, Cohen DL, Townsend RR: Cardiovascular events and mortality in white coat hypertension: A systematic review and meta-analysis. Ann Intern Med 170: 853862, 2019 PubMed

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  • 20

    Hundemer GL, Kline GA, Leung AA: How common is primary aldosteronism? Curr Opin Nephrol Hypertens 30: 353360, 2021 PubMed

  • 21

    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 101: 18891916, 2016 PubMed

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  • 22

    Hundemer GL, Baudrand R, Brown JM, Curhan G, Williams GH, Vaidya A: Renin phenotypes characterize vascular disease, autonomous aldosteronism, and mineralocorticoid receptor activity. J Clin Endocrinol Metab 102: 18351843, 2017 PubMed

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  • 23

    Vasan RS, Evans JC, Larson MG, Wilson PW, Meigs JB, Rifai N, et al.: Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 351: 3341, 2004 PubMed

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  • 24

    Newton-Cheh C, Guo CY, Gona P, Larson MG, Benjamin EJ, Wang TJ, et al.: Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample. Hypertension 49: 846856, 2007 PubMed

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  • 25

    Kim SK, McCurley AT, DuPont JJ, Aronovitz M, Moss ME, Stillman IE, et al.: Smooth muscle cell-mineralocorticoid receptor as a mediator of cardiovascular stiffness with aging. Hypertension 71: 609621, 2018 PubMed

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  • 26

    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 6: 4150, 2018 PubMed

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  • 27

    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 2: e93136, 2017 PubMed

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  • 28

    Monticone S, Sconfienza E, D’Ascenzo F, Buffolo F, Satoh F, Sechi LA, et al.: Renal damage in primary aldosteronism: A systematic review and meta-analysis. J Hypertens 38: 312, 2020 PubMed

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  • 29

    Cohen JB, Cohen DL, Herman DS, Leppert JT, Byrd JB, Bhalla V: Testing for primary aldosteronism and mineralocorticoid receptor antagonist use among U.S. veterans: A retrospective cohort study. Ann Intern Med 174: 289297, 2021 PubMed

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  • 30

    Hundemer GL, Imsirovic H, Vaidya A, Yozamp N, Goupil R, Madore F, et al.: Screening rates for primary aldosteronism among individuals with hypertension plus hypokalemia: A population-based retrospective cohort study. Hypertension 79: 178186, 2021 PubMed

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  • 31

    Hundemer GL, Vaidya A: Primary aldosteronism diagnosis and management: A clinical approach. Endocrinol Metab Clin North Am 48: 681700, 2019 PubMed

  • 32

    Hung A, Ahmed S, Gupta A, Davis A, Kline GA, Leung AA, et al.: Performance of the aldosterone-to-renin ratio as a screening test for primary aldosteronism: A systematic review and meta-analysis. J Clin Endocrinol Metab 106: 24232435, 2021

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  • 33

    Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, et al.: Systematic review: Diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med 151: 329337, 2009 PubMed

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  • 34

    Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, et al.; Primary Aldosteronism Surgery Outcome (PASO) investigators: 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 5: 689699, 2017 PubMed

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  • 35

    Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A: Renal outcomes in medically and surgically treated primary aldosteronism. Hypertension 72: 658666, 2018 PubMed

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  • 36

    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 6: 5159, 2018 PubMed

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  • 37

    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 3: 768774, 2018 PubMed

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  • 38

    Köhler A, Sarkis AL, Heinrich DA, Müller L, Handgriff L, Deniz S, et al.: Renin, a marker for left ventricular hypertrophy, in primary aldosteronism: A cohort study. Eur J Endocrinol 185: 663672, 2021 PubMed

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  • 39

    Baudrand R, Guarda FJ, Torrey J, Williams G, Vaidya A: Dietary sodium restriction increases the risk of misinterpreting mild cases of primary aldosteronism. J Clin Endocrinol Metab 101: 39893996, 2016 PubMed

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    De Nicola L, Gabbai FB, Agarwal R, Chiodini P, Borrelli S, Bellizzi V, et al.: Prevalence and prognostic role of resistant hypertension in chronic kidney disease patients. J Am Coll Cardiol 61: 24612467, 2013 PubMed

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    Chee MR, Hoo J, Libianto R, Gwini SM, Hamilton G, Narayan O, et al.: Prospective screening for primary aldosteronism in patients with suspected obstructive sleep apnea. Hypertension 77: 20942103, 2021 PubMed

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    Yang L, Zhang H, Cai M, Zou Y, Jiang X, Song L, et al.: Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea. Clin Exp Hypertens 38: 464468, 2016 PubMed

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    Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al.; British Hypertension Society’s PATHWAY Studies Group: Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): A randomised, double-blind, crossover trial. Lancet 386: 20592068, 2015 PubMed

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