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Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes

Journal of Human Hypertension volume 28, pages 213–217 (2014)Cite this article

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Abstract

Among the vast population of hypertensive subjects, between 10 and 15% do not achieve an adequate blood pressure (BP) control despite the use of at least three antihypertensive agents. This group, designated as having resistant hypertension (RH), represents one of the most important clinical challenges in hypertension evaluation and management. Resistant hypertensives are characterized by several clinical particularities, such as a longer history of hypertension, obesity and other accompanying factors, such as diabetes, left ventricular hypertrophy, albuminuria and renal dysfunction. In addition to other diagnostic and therapeutic maneuvers, such as excluding secondary hypertension, ensuring treatment adherence and optimizing therapeutic schemes, ambulatory BP monitoring (ABPM) is crucial in the clinical evaluation of patients with RH. ABPM distinguish between those with out-of-office BP elevation (true resistant hypertensives) and those having white-coat RH (WCRH; normalcy of 24-h BPs), the prevalence of the latter estimated in about one-third of the population with RH. True resistant hypertensives also exhibit more frequently other co-morbidities, more severe target organ damage and a worse cardiovascular prognosis, in comparison to those with WCRH. Some device-based therapies have recently been developed for treatment of RH. This requires a better characterization of a potential candidate population. A better knowledge of the clinical features of resistant hypertensive subjects, the confirmation of elevated BP values out of the doctor’s office, and improvements in the search for secondary causes would help to select those candidates for newer therapies, once the pharmacological possibilities have been exhausted.

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References

  1. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD et alAmerican Heart Association Professional Education Committee.. 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. Hypertension 2008; 51: 1403–1419.

    Article  CAS  PubMed  Google Scholar 

  2. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M et al. 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: 1281–1357.

    Article  CAS  PubMed  Google Scholar 

  3. 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: 898–902.

    Article  CAS  PubMed  Google Scholar 

  4. 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 (Greenwich) 2012; 14: 7–12.

    Article  Google Scholar 

  5. Persell SD . Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension 2011; 57: 1076–1080.

    Article  CAS  PubMed  Google Scholar 

  6. 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: 1635–1642.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Brown MA, Buddle ML, Martin A . Is resistant hypertension really resistant? Am J Hypertens 2001; 14: 1263–1269.

    Article  CAS  PubMed  Google Scholar 

  8. Cuspidi C, Sala C, Valerio C, Negri F, Mancia G . Nocturnal hypertension and organ damage in dippers and nondippers. Am J Hypertens 2012; 25: 869–875.

    Article  PubMed  Google Scholar 

  9. Oliveras A, Armario P, Martell N, Ruilope LM, de la Sierra A . Urinary albumin excretion is associated with nocturnal systolic blood pressure in resistant hypertensives. Hypertension 2011; 57: 556–560.

    Article  CAS  PubMed  Google Scholar 

  10. Muxfeldt ES, Salles GF . How to use ambulatory blood pressure monitoring in resistant hypertension. Hypertens Res 2013; 36: 385–389.

    Article  PubMed  Google Scholar 

  11. Muxfeldt ES, Bloch KV, Nogueira AR, Salles GF . True resistant hypertension: is it possible to be recognized in the office? Am J Hypertens 2005; 18: 1534–1540.

    Article  PubMed  Google Scholar 

  12. 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 2012; 30: 1211–1216.

    Article  CAS  PubMed  Google Scholar 

  13. 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: 1422–1428.

    Article  PubMed  Google Scholar 

  14. Redon J, Campos C, Narciso ML, Rodicio JL, Pascual JM, Ruilope LM . Prognostic value of ambulatory blood pressure monitoring in refractory hypertension. A prospective study. Hypertension 1998; 31: 712–718.

    Article  CAS  PubMed  Google Scholar 

  15. Salles GF, Cardoso CRL, Muxfeldt ES . Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med 2008; 168: 2340–2346.

    Article  PubMed  Google Scholar 

  16. De la Sierra A . Profile of ambulatory blood pressure in resistant hypertension. Hypertens Res 2013; 36 (7): 565–569.

    Article  PubMed  Google Scholar 

  17. 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: 69–76.

    Article  CAS  PubMed  Google Scholar 

  18. Muxfeldt ES, Fiszman R, de Souza F, Viegas B, Oliveira FC, Salles GF . Appropriate time interval to repeat ambulatory blood pressure monitoring in patients with white-coat resistant hypertension. Hypertension 2012; 59: 384–389.

    Article  CAS  PubMed  Google Scholar 

  19. 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: 1046–1058.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Oliveras A, Armario P, Hernández-del Rey R, Arroyo JA, Poch E, Larrousse M et al. Urinary albumin excretion is associated with true resistant hypertension. J Hum Hypertens 2010; 24: 27–33.

    Article  CAS  PubMed  Google Scholar 

  21. Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P . Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40: 892–896.

    Article  CAS  PubMed  Google Scholar 

  22. Eide IK, Torjesen PA, Drolsum A, Babovic A, Lilledahl NP . Low-renin status in therapy-resistant hypertension: a clue to efficient treatment. J Hypertens 2004; 22: 2217–2226.

    Article  CAS  PubMed  Google Scholar 

  23. Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, Pimenta E, Aban I, Oparil S et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volumen expansion. Arch Intern Med 2008; 168: 1159–1164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chapman N, Dobson J, Wilson S, Dahlöf B, Sever PS, Wedel H et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension 2007; 49: 839–845.

    Article  CAS  PubMed  Google Scholar 

  25. de Souza F, Muxfeldt E, Fiszman R, Salles G . Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension 2010; 55: 147–152.

    Article  CAS  PubMed  Google Scholar 

  26. Václavík J, Sedlák R, Plachy M, Navrátil K, Plásek J, Jarkovsky J et al. Addition of Spironolactone in Patients With Resistant Arterial Hypertension (ASPIRANT) A randomized, double-blind, placebo-controlled trial. Hypertension 2011; 57: 1069–1075.

    Article  PubMed  Google Scholar 

  27. Alvarez-Alvarez B, Abad-Cardiel M, Fernandez-Cruz A, Martell-Claros N . Management of resistant arterial hypertension: role of spironolactone versus double blockade of the renin-angiotensin-aldosterone system. J Hypertens 2010; 28: 2329–2335.

    Article  CAS  PubMed  Google Scholar 

  28. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg HS, Barthel A et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA 2003; 100: 14211–14216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gonzaga CC, Gaddam KK, Ahmed MI, Pimenta E, Thomas SJ, Harding SM et al. Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension. J Clin Sleep Med 2010; 6: 363–368.

    PubMed Central  PubMed  Google Scholar 

  30. 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: 811–817.

    Article  CAS  PubMed  Google Scholar 

  31. Pimenta E, Stowasser M, Gordon RD, Harding SM, Batlouni M, Zhang B et al. Increased dietary sodium is related to severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism. Chest 2013; 143: 978–983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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: 152–158.

    Article  PubMed  Google Scholar 

  33. Symplicity HTN-1Investigators. Catheter-based renal sympathetic denervation for resistant hypertension. Durability of blood pressure reduction out to 24 months. Hypertension 2011; 57: 911–917.

    Article  Google Scholar 

  34. Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M . Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 2010; 376: 1903–1909.

    Article  PubMed  Google Scholar 

  35. Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V et al. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens 2001; 19: 2063–2070.

    Article  CAS  PubMed  Google Scholar 

  36. De la Sierra A, Larrousse M, Oliveras A, Armario P, Hernández del Rey R, Poch E et al. Abnormalities of vascular function in resistant hypertension. Blood Press 2012; 21: 104–109.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Hospital del Mar, Barcelona, Spain

    A Oliveras

  2. Department of Internal Medicine, Hospital Mutua Terrassa, University of Barcelona, Terrassa, Spain

    A de la Sierra

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  1. A Oliveras
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  2. A de la Sierra
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Correspondence to A de la Sierra.

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Oliveras, A., de la Sierra, A. Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes. J Hum Hypertens 28, 213–217 (2014). https://doi.org/10.1038/jhh.2013.77

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