Resistant hypertension: clinical approach

Authors

  • Elizabeth Silaid Muxfeldt Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Medicina - Rio de Janeiro (RJ), Brasil. http://orcid.org/0000-0003-3853-7842
  • Bernardo Fróes Chedier Barreira Universidade Federal do Rio de Janeiro (UFRJ), Faculdade de Medicina - Rio de Janeiro (RJ), Brasil. http://orcid.org/0000-0001-8381-9561
  • Cibele Isaac Saad Rodrigues Pontifícia Universidade Católica de São Paulo (PUC-SP), Faculdade de Ciências Médicas e da Saúde (FCMS) - Sorocaba (SP), Brasil. http://orcid.org/0000-0001-9490-7997

DOI:

https://doi.org/10.23925/1984-4840.2018v20i3a3

Keywords:

blood pressure, hypertension, sympathetic nervous system, hyperaldosteronism, drug resistance, antihypertensive agents

Abstract

Resistant hypertension is defined as an uncontrolled office blood pressure in spite of the use of at least 3 anti-hypertensive drugs, ideally including a diuretic. Individuals using four or more medications with blood pressure control are also considered resistant hypertensives. Furthermore, refractory hypertension is defined as uncontrolled blood pressure despite the use of 5 or more drugs, including a long-acting thiazide diuretic and a aldosterone antagonist. Its increasing prevalence is associated with a progressive ageing of the population and the progression of obesity, related to a high cardiovascular and renal morbidity and mortality. The diagnostic approach is based on four steps: eliminate pseudoresistance, identify the white-coat effect phenomenon, investigate secondary causes of hypertension and identify target organ damage aiming at stratification of cardiovascular risk. The therapeutic objective is the controlof 24-hour blood pressure. Lifestyle changes must be stimulated and the first three drugs should include an adequate diuretic, a renin angiotensin-aldosterone-system inhibitor and a calcium channel blocker. Persisting an uncontrolled blood pressure, a fourth drug is added: spironolactone. Regarding the treatment of refractory hypertension, new therapeutic modalities have been developed as renal denervation and baroreflex stimulation.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, et al. Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117(25):e510-26. https://doi.org/10.1161/CIRCULATIONAHA.108.189141

Muxfeldt ES, Souza F, Margallo VS, Salles GF. Cardiovascular and renal complications in patients with resistant hypertension. Curr Hypertens Rep. 2014;16(9):471. https://doi.org/10.1007/s11906-014-0471-7

Acelajado MC, Pisoni R, Dudenbostel T, Dell’Italia LJ, Cartmill F, Zhang B, et al. Refractory hypertension: definition, prevalence, and patient characteristics. J Clin Hypertens. 2012;14(1):7-12. https://doi.org/10.1111/j.1751-7176.2011.00556.x

Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, 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). J Hypertens. 2013;31(7):1281-357. https://doi.org/10.1097/01.hjh.0000431740.32696.cc

Picon RV, Fuchs FD, Moreira LB, Riegel G, Fuchs SC. Trends in prevalence of hypertension in Brazil: a systematic review with metaanalysis. PLoS One. 2012;7(10):e48255. https://doi.org/10.1371/journal.pone.0048255

Malachias MVB, Souza WKSB, Plavnik FL, Rodrigues CIS, Brandão AA, Neves MFT, et al. 7ª Diretriz Brasileira de Hipertensão Arterial. Arq Bras Cardiol. 2016;107(3Supl.3):1-83. http://dx.doi.org/10.5935/abc.20160153

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. 2011;57(5):898-902. https://doi.org/10.1161/HYPERTENSIONAHA.110.168948

Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension. 2011;57:1076-80. https://doi.org/10.1161/HYPERTENSIONAHA.111.170308

Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012;125(13):1635-42. https://doi.org/10.1161/CIRCULATIONAHA.111.068064

Sim JJ, Bhandari SK, Shi J, Liu IL, Calhoun DA, McGlynn EA, et al. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system. Mayo Clin Proc. 2013;88(10):1099-107. https://doi.org/10.1016/j.mayocp.2013.06.017

Lotufo PA, Pereira AC, Vasconcellos PS, Santos IS, Mill JG, Bensenor IM. Resistant hypertension: risk factors, subclinical atherosclerosis, and comorbidities among adults-the Brazilian longitudinal study of adult health (ELSA-Brazil). J Clin Hypertens. 2015;17(1):74-80. https://doi.org/10.1111/jch.12433

Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011;124(9):1046-58. https://doi.org/10.1161/CIRCULATIONAHA.111.030189

Calhoun DA, Booth JN, Oparil S, Irvin MR, Shimbo D, Lackland DT, et al. Refractory hypertension: determination of prevalence, risk factors, and comorbidities in a large, population-based cohort. Hypertension. 2014;63(3):451-8. https://doi.org/10.1161/HYPERTENSIONAHA.113.02026

Dudenbostel T, Siddiqui M, Oparil S, Calhoun DA. Refractory hypertension: a novel phenotype of antihypertensive treatment failure. Hypertension. 2016;67(6):1085-92. https://doi.org/10.1161/HYPERTENSIONAHA.116.06587

Armario P, Calhoun DA, Oliveras A, Blanch P, Vinyoles E, Banegas JR, et al. Prevalence and clinical characteristics of refractory hypertension. J Am Heart Assoc. 2017;6(12):pii:e007365. https://doi.org/10.1161/JAHA.117.007365

Alessi A, Brandão AA, Coca A, Cordeiro AC, Nogueira AR, Diógenes de Magalhães F, et al. I posicionamento brasileiro sobre hipertensão arterial resistente. Arq Bras Cardiol. 2012;99(1):576-85. http://dx.doi.org/10.1590/S0066-782X2012001000002

Fontes-Guerra PC, Cardoso CR, Muxfeldt ES, Salles GF. Nitroglycerin-mediated, but not flow-mediated vasodilation, is associated with blunted nocturnal blood pressure fall in patients with resistant hypertension. J Hypertens. 2015;33(8):1666-75. https://doi.org/10.1097/HJH.0000000000000589

Roderjan CN, Cardoso CR, Ferreira MT, Muxfeldt ES, Salles GF. Correlates of aortic stiffness progression in patients with resistant hypertension: importance of clinic and ambulatory blood pressure changes. J Hypertens. 2015;33(4):827-34. https://doi.org/10.1097/HJH.0000000000000491

Modolo R, Faria AP, Almeida A, Moreno H. Resistant or refractory hypertension: are they different? Curr Hypertens Rep. 2014;16(10):485-92. https://doi.org/10.1007/s11906-014-0485-1

Calhoun DA. Hyperaldosteronism as a common cause of resistant hypertension. Annu Rev Med. 2013;64:233-47. https://doi.org/10.1146/annurev-med-042711-135929

Yugar-Toledo JC, Modolo R, Faria AP, Moreno H. Managing resistant hypertension: focus on mineralocorticoid-receptor antagonists. Vasc Health Risk Manag. 2017;13:403-11. https://doi.org/10.2147/VHRM.S138599

Dudenbostel T, Acelajado MC, Pisoni R, Li P, Oparil S, Calhoun D. Refractory hypertension: evidence of heightened sympathetic activity as a cause of antihypertensive treatment failure. Hypertension. 2015;66(1):126-33. https://doi.org/10.1161/HYPERTENSIONAHA.115.05449

Siddiqui M, Calhoun DA. Refractory versus resistant hypertension. CurrOpinNephrolHypertens. 2017;26(1):14- 9. https://doi.org/10.1097/MNH.0000000000000286

Muxfeldt ES, Salles GF. Pulse pressure or dipping pattern: which one is a better cardiovascular risk marker in resistant hypertension? J Hypertens. 2008;26(5):878- 84. https://doi.org/10.1097/HJH.0b013e3282f55021

Muxfeldt ES, Margallo VS, Guimarães GM, Salles GF. Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens. 2014;27(8):1069-78. https://doi.org/10.1093/ajh/hpu023

Muxfeldt ES, Souza F, Salles GF. Resistant hypertension: a practical clinical approach. J Hum Hypertens. 2013;27(11):657-62. https://doi.org/10.1038/jhh.2013.34

Braam B, Taler SJ, Rahman M, Fillaus JA, Greco BA, Forman JP, et al. Recognition and management of resistant hypertension. Clin J Am Soc Nephrol. 2017;12(3):524-35. https://doi.org/10.2215/CJN.06180616

Judd E, Calhoun DA. Apparent and true resistant hypertension: definition, prevalence and outcomes. J Hum Hypertens. 2014;28(8):463-8. https://doi.org/10.1038/jhh.2013.140

Garg JP, Elliott WJ, Folker, Izhar M, Black HR, RUSH University Hypertension Service. Resistant hypertension revisited: a comparison of two universitybased cohorts. Am J Hypertens. 2005;18(5Pt.1):619-26. https://doi.org/10.1016/j.amjhyper.2004.11.021

Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001;344(1):3-10. https://doi.org/10.1056/NEJM200101043440101

Burnier M, Wuerzner G, Struijker-Boudier H, Urquhart J. Measuring, analyzing, and managing drug adherence in resistant hypertension. Hypertension. 2013;62(2):218-25. https://doi.org/10.1161/HYPERTENSIONAHA.113.00687

Wojciechowska W, Stolarz-Skrzypek K, Olszanecka A, Klima Ł, Gąsowski J, Grodzicki T, et al. Subclinical arterial and cardiac damage in white-coat and masked hypertension. Blood Press. 2016;25(4):249-56. https://doi.org/10.3109/08037051.2016.1150563

Muxfeldt ES, Salles GF. How to use ambulatory blood pressure monitoring in resistant hypertension. Hypertens Res. 2013;36(5):385-9. https://doi.org/10.1038/hr.2013.17

Salles G. Cardoso CRL, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med. 2008;168(21):2340-6. https://doi.org/10.1001/archinte.168.21.2340

Hermida RC, Ayala DE, Mojón A, Fernández JR. Effects of time of antihypertensive treatment on ambulatory blood pressure and clinical characteristics of subjects with resistant hypertension. Am J Hypertens. 2010;23(4):432-9. https://doi.org/10.1038/ajh.2009.260

Hermida RC, Ayala DE, Fernández JR, Mojón A, Crespo JJ, Ríos MT, et al. Bedtime blood pressure chronotherapy significantly improves hypertension management. Heart Fail Clin. 2017;13(4):759-73. https://doi.org/10.1016/j.hfc.2017.05.010

Hermida RC, Ayala DE, Fernández JR, Calvo C. Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. Hypertension. 2008;51(1):69-76. https://doi.org/10.1161/HYPERTENSIONAHA.107.096933

Muxfeldt ES, Cardoso CRL, Salles GF. Prognostic value of nocturnal blood pressure reduction in resistant hypertension. Arch Intern Med. 2009;169(9):874-80. https://doi.org/10.1001/archinternmed.2009.68

Pedrosa RP, Drager LF, Gonzaga CC, Sousa MG, de Paula LK, Amaro AC, et al. Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension. Hypertension. 2011;58(5):811-7. https://doi.org/10.1161/HYPERTENSIONAHA.111.179788

Oliveras A, Armario P, Sierra C, Arroyo JA, Hernández- Del-Rey R, Vazquez S, et al. Urinary albumin excretion at follow-up predicts cardiovascular outcomes in subjects with resistant hypertension. Am J Hypertens. 2013;26(9):1148-54. https://doi.org/10.1093/ajh/hpt074

Costa PM, Cortez AF, Souza F, Mares GS, Santos BDM, Muxfeldt ES. Prognostic impact of baseline urinary albumin excretion rate in patients with resistant hypertension: a prospective cohort study. J Hum Hypertens. 2018;32(2):139-49. https://doi.org/10.1038/s41371-017-0013-2

Salles GF, Cardoso CRL, Fiszman R, Muxfeldt ES. Prognostic importance of baseline and serial changes in microalbuminuria in patients with resistant hypertension. Atherosclerosis. 2011;216(1):199-204. https://doi.org/10.1016/j.atherosclerosis.2011.01.026

Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H, et al. Anglo-Scandinavian Cardiac Outcomes Trial Investigators. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49(4):839-45. https://doi.org/10.1161/01.HYP.0000259805.18468.8c

Souza F, Muxfeldt ES, Fiszman R, Salles GF. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010;55(1):147-52. https://doi.org/10.1161/HYPERTENSIONAHA.109.140988

Dudenbostel T, Calhoun DA. Use of aldosterone antagonists for treatment of uncontrolled resistant hypertension. Am J Hypertens. 2017;30(2):103-9. https://doi.org/10.1093/ajh/hpw105

Pisoni R, Acelajado MC, Cartmill FR, Dudenbostel T, Dell’Italia LJ, Cofield SS, et al. Long-term effects of aldosterone blockade in resistant hypertension associated with chronic kidney disease. J Hum Hypertens. 2012;26(8):502-6. https://doi.org/10.1038/jhh.2011.60

Abolghasmi R, Taziki O. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. Saudi J Kidney Dis Transpl. 2011;22(1):75-8.

Krieger EM, Drager LF, Giorgi DMA, Pereira AC, Barreto-Filho JAS, Nogueira AR, et al. Spironolactone versus clonidine as a fourth-drug therapy for resistant hypertension. The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment). Hypertension. 2018;71(4):681-90. https://doi.org/10.1161/HYPERTENSIONAHA.117.10662

Krum H, Schlaich MP, Sobotka PA, Böhm M, Mahfoud F, Rocha-Singh K, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the Symplicity HTN-1 study. Lancet. 2014;383(9917):P622-9. https://doi.org/10.1016/S0140-6736(13)62192-3

Esler MD, Böhm M, Sievert H, Rump CL, Schmieder RE, Krum H, et al. Catheter-based renal denervation for treatment of patients with treatmentresistant hypertension: 36 month results from the SYMPLICITY HTN-2 randomized clinical trial. Eur Heart J. 2014;35(26):1752-9. https://doi.org/10.1093/eurheartj/ehu209

Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393-401. https://doi.org/10.1056/NEJMoa1402670

Schlaich MP. Renal sympathetic denervation: a viable option for treating resistant hypertension. Am J Hypertens. 2017;30(9):847-56. https://doi.org/10.1093/ajh/hpx033

Fadl Elmula F, Jin Y, Larstorp AC, Persu A, Kjeldsen SE, Staessen JA. Meta-analysis of five prospective and randomized trials of renal sympathetic denervation on office and ambulatory systolic blood pressure in treatment resistant hypertension. J Hypertens. 2015;33(Supl.1):e107. https://doi.org/10.1097/01.hjh.0000467637.16752.63

Fadl Elmula F, Jin Y, Yang WY, Thijs L, Lu YC, Larstorp AC, et al. European Network Coordinating Research On Renal Denervation (ENCOReD) Consortium. Meta-analysis of randomized controlled trials on renal denervation in treatment-resistant hypertension. Blood Press. 2015;24(5):263-74. https://doi.org/10.3109/08037051.2015.1058595

Coppolino G, Pisano A, Rivoli L, Bolignano D. Renal denervation for resistant hypertension. Cochrane Database System Rev. 2017;(2):CD011499. https://doi.org/10.1002/14651858.CD011499.pub2

Scheffers IJ, Kroon AA, Schmidli J, Jordan J, Tordoir JJ, Mohaupt MG, et al. Novel baroreflex activation therapy in resistant hypertension results of a European multi-center feasibility study. J Am Coll Cardiol. 2010;56(15):1254- 8. https://doi.org/10.1016/j.jacc.2010.03.089

Bakris GL, Nadim MK, Haller H, Lovett EG, Schafer JE, Bisognano JD. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. 2012;6(2):152-8. https://doi.org/10.1016/j.jash.2012.01.003

de Leeuw PW, Bisognano JD, Bakris GL, Nadim MK, Haller H, Kroon AA, et al. Sustained reduction of blood pressure with baroreceptor activation therapy: results of the 6-year open follow-up. Hypertension. 2017;69(5):836-43. https://doi.org/10.1161/HYPERTENSIONAHA.117.09086

Lobo MD, Sobotka PA, Stanton A, Cockcroft JR, Sulke N, Dolan E, et al. Central arteriovenous anastomosis for the treatment of patients with uncontrolled hypertension (the ROX CONTROL HTN study): a randomised controlled trial. Lancet. 2015;385(9978):P1634-41. https://doi.org/10.1016/S0140-6736(14)62053-5

Bertog SC, Sobotka NA, Sobotka PA, Lobo MD, Sievert K, Vaskelyte L, et al. Percutaneous creation of a central iliac arteriovenous anastomosis for the treatment of arterial hypertension. Curr Hypertens Rep. 2018;20(3):18. https://doi.org/10.1007/s11906-018-0816-8

Kapil V, Sobotka PA, Lobo MD, Schmieder RE. Central arteriovenous anastomosis to treat resistant hypertension. Curr Opin Nephrol Hypertens. 2018;27(1):8-15. https://doi.org/10.1097/MNH.0000000000000379

Souza F, Muxfeldt ES, Salles GF. Prognostic factors in resistant hypertension: implications for cardiovascular risk stratification and therapeutic management. Expert Rev Cardiovasc Ther. 2012;10(6):735-45. https://doi.org/10.1586/erc.12.58

Pierdomenico SD, Lapenna D, Bucci A, Di Tommaso R, Di Mascio R, Manente BM, et al. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens. 2005;18(11):1422-8. https://doi.org/10.1016/j.amjhyper.2005.05.014

Salles GF, Cardoso CR, Muxfeldt ES. Prognostic value of ventricular repolarization prolongation in resistant hypertension: a prospective cohort study. J Hypertens. 2009;27(5):1094-101. https://doi.org/10.1097/HJH.0b013e32832720b3

Salles GF, Cardoso CR, Fiszman R, Muxfeldt ES. Prognostic impact of baseline and serial changes in electrocardiographic left ventricular hypertrophy in resistant hypertension. Am Heart J. 2010;159(5):833- 40. https://doi.org/10.1016/j.ahj.2010.02.012

Salles GF, Cardoso CR, Fiszman R, Muxfeldt ES. Prognostic significance of baseline and serial changes in electrocardiographic strain pattern in resistant hypertension. J Hypertens. 2010;28(8):1715-23. https://doi.org/10.1097/HJH.0b013e32833af39a

Cortez AF, Muxfeldt ES, Cardoso CR, Salles GF. Prognostic value of C-reactive protein in resistant hypertension. Am J Hypertens. 2016;29(8):992-1000. https://doi.org/10.1093/ajh/hpw011

Published

2018-12-03

How to Cite

1.
Muxfeldt ES, Barreira BFC, Rodrigues CIS. Resistant hypertension: clinical approach. Rev. Fac. Ciênc. Méd. Sorocaba [Internet]. 2018Dec.3 [cited 2024Dec.21];20(3):128-37. Available from: https://revistas.pucsp.br/index.php/RFCMS/article/view/37646

Issue

Section

Review