American Journal of Internal Medicine

| Peer-Reviewed |

The Obstinate Refractory and Resistance Hypertension

Received: 17 April 2020    Accepted: 03 August 2020    Published: 20 August 2020
Views:       Downloads:

Share This Article

Abstract

Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed.

DOI 10.11648/j.ajim.20200805.13
Published in American Journal of Internal Medicine (Volume 8, Issue 5, September 2020)
Page(s) 211-214
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Aldosterone, Antihypertensive Treatment Failure, Treatment Resistance, Sympathetic Activity, Volume Dependent

References
[1] Van Dyne JR. Iproniazid in the treatment of resistant hypertension. A preliminary report on twenty intractable cases. J Am Geriatr Soc. 1960; 8: 454–62. [PubMed] [Google Scholar].
[2] Lee RE, et al. Therapeutically refractory hypertension: causative factors, and medical management with chlorothiazide and other agents. Ann Intern Med. 1958; 49 (5): 1129–37. [PubMed] [Google Scholar].
[3] Calhoun DA, 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. Hypertension. 2008; 51 (6): 1403–19. [PubMed] [Google Scholar].
[4] Acelajado MC, et al. Refractory hypertension: definition, prevalence, and patient characteristics. J Clin Hypertens (Greenwich) 2012; 14 (1): 7–12. [PMC free article] [PubMed] [Google Scholar].
[5] Calhoun DA, et al. Refractory hypertension: determination of prevalence, risk factors, and comorbidities in a large, population-based cohort. Hypertension. 2014; 63 (3): 451–8. [PMC free article] [PubMed] [Google Scholar].
[6] Dudenbostel T, et al. Refractory Hypertension: Evidence of Heightened Sympathetic Activity as a Cause of Antihypertensive Treatment Failure. Hypertension. 2015; 66 (1): 126–33. [PMC free article] [PubMed] [Google Scholar].
[7] de la Sierra A, 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. [PubMed] [Google Scholar].
[8] Sim JJ, 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. [PMC free article] [PubMed] [Google Scholar].
[9] Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension. 2011; 57 (6): 1076–80. [PubMed] [Google Scholar].
[10] Egan BM, et al. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011; 124 (9): 1046–58. [PMC free article] [PubMed] [Google Scholar].
[11] Modolo R, et al. Refractory and resistant hypertension: characteristics and differences observed in a specialized clinic. J Am Soc Hypertens. 2015; 9 (5): 397–402. [PubMed] [Google Scholar].
[12] Grigoryan L, Pavlik VN, Hyman DJ. Characteristics, drug combinations and dosages of primary care patients with uncontrolled ambulatory blood pressure and high medication adherence. J Am Soc Hypertens. 2013; 7 (6): 471–6. [PMC free article] [PubMed] [Google Scholar].
[13] Muxfeldt ES, et al. True resistant hypertension: is it possible to be recognized in the office? Am J Hypertens. 2005; 18 (12 Pt 1): 1534–40. [PubMed] [Google Scholar].
[14] Pickering TG, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005; 111 (5): 697–716. [PubMed] [Google Scholar].
[15] Bhatt H, et al. Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement. J Am Soc Hypertens. 2016; 10 (6): 493–9. [PMC free article] [PubMed] [Google Scholar].
[16] Jung O, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens. 2013; 31 (4): 766–74. [PubMed] [Google Scholar].
[17] Strauch B, et al. Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis. J Hypertens. 2013; 31 (12): 2455–61. [PubMed] [Google Scholar].
[18] Weitzman D, et al. Prevalence and factors associated with resistant hypertension in a large health maintenance organization in Israel. Hypertension. 2014; 64 (3): 501–7. [PubMed] [Google Scholar].
[19] Hwang AY, Dave C, Smith SM. Trends in Antihypertensive Medication Use Among US Patients With Resistant Hypertension, 2008 to 2014. Hypertension. 2016; 68 (6): 1349–1354. [PubMed] [Google Scholar].
[20] Fadl Elmula FE, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014; 63 (5): 991–9. [PubMed] [Google Scholar].
[21] Williams B, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015; 386 (10008): 2059–68. [PMC free article] [PubMed] [Google Scholar].
[22] Siddiqui M, et al. White Coat Effect Is Uncommon in Patients With Refractory Hypertension. Hypertension. 2017 [PMC free article] [PubMed] [Google Scholar].
[23] Khosla N, et al. Are chlorthalidone and hydrochlorothiazide equivalent blood-pressure-lowering medications? J Clin Hypertens (Greenwich) 2005; 7 (6): 354–6. [PubMed] [Google Scholar].
[24] Gaddam K, et al. Rapid reversal of left ventricular hypertrophy and intracardiac volume overload in patients with resistant hypertension and hyperaldosteronism: a prospective clinical study. Hypertension. 2010; 55 (5): 1137–42. [PMC free article] [PubMed] [Google Scholar].
[25] Gaddam KK, et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch Intern Med. 2008; 168 (11): 1159–64. [PMC free article] [PubMed] [Google Scholar].
[26] Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension. 2002; 39 (5): 982–8. [PubMed] [Google Scholar].
Author Information
  • JLN Medical College, Aryabhatta University, Bhagalpur, Bihar, India

  • JLN Medical College, Aryabhatta University, Bhagalpur, Bihar, India

Cite This Article
  • APA Style

    Raj Kamal Choudhry, Amrendra Kumar Singh. (2020). The Obstinate Refractory and Resistance Hypertension. American Journal of Internal Medicine, 8(5), 211-214. https://doi.org/10.11648/j.ajim.20200805.13

    Copy | Download

    ACS Style

    Raj Kamal Choudhry; Amrendra Kumar Singh. The Obstinate Refractory and Resistance Hypertension. Am. J. Intern. Med. 2020, 8(5), 211-214. doi: 10.11648/j.ajim.20200805.13

    Copy | Download

    AMA Style

    Raj Kamal Choudhry, Amrendra Kumar Singh. The Obstinate Refractory and Resistance Hypertension. Am J Intern Med. 2020;8(5):211-214. doi: 10.11648/j.ajim.20200805.13

    Copy | Download

  • @article{10.11648/j.ajim.20200805.13,
      author = {Raj Kamal Choudhry and Amrendra Kumar Singh},
      title = {The Obstinate Refractory and Resistance Hypertension},
      journal = {American Journal of Internal Medicine},
      volume = {8},
      number = {5},
      pages = {211-214},
      doi = {10.11648/j.ajim.20200805.13},
      url = {https://doi.org/10.11648/j.ajim.20200805.13},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ajim.20200805.13},
      abstract = {Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed.},
     year = {2020}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - The Obstinate Refractory and Resistance Hypertension
    AU  - Raj Kamal Choudhry
    AU  - Amrendra Kumar Singh
    Y1  - 2020/08/20
    PY  - 2020
    N1  - https://doi.org/10.11648/j.ajim.20200805.13
    DO  - 10.11648/j.ajim.20200805.13
    T2  - American Journal of Internal Medicine
    JF  - American Journal of Internal Medicine
    JO  - American Journal of Internal Medicine
    SP  - 211
    EP  - 214
    PB  - Science Publishing Group
    SN  - 2330-4324
    UR  - https://doi.org/10.11648/j.ajim.20200805.13
    AB  - Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed.
    VL  - 8
    IS  - 5
    ER  - 

    Copy | Download

  • Sections