DOI QR코드

DOI QR Code

Refractory and Resistant Hypertension: Antihypertensive Treatment Failure versus Treatment Resistance

  • Calhoun, David A. (Vascular Biology and Hypertension Program, University of Alabama at Birmingham)
  • Received : 2015.12.24
  • Accepted : 2016.03.17
  • Published : 2016.09.30

Abstract

Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension. Risk factors for refractory hypertension include obesity, diabetes, chronic kidney disease, and especially, being of African origin. Patients with refractory are at high cardiovascular risk based on increased rates of known heart disease, prior stroke, and prior episodes of congestive heart failure. Mechanisms of refractory hypertension need exploration, but early studies suggest a possible role of heightened sympathetic tone as evidenced by increased office and ambulatory heart rates and higher urinary excretion of norepinephrine compared to patients with controlled resistant hypertension. Important negative findings argue against refractory hypertension being fluid dependent as is typical of resistant hypertension, including aldosterone levels, dietary sodium intake, and brain natriuretic peptide levels being similar or even less than patients with resistant hypertension and the failure to control blood pressure with use of intensive diuretic therapy, including both a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Further studies, especially longitudinal assessments, are needed to better characterize this extreme phenotype in terms of risk factors and outcomes and hopefully to identify effective treatment strategies.

Keywords

References

  1. Gifford RW Jr. Resistant hypertension. Introduction and definitions. Hypertension 1988;11(3 Pt 2):II65-6.
  2. Calhoun DA, Jones D, Textor S, 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;51:1403-19. https://doi.org/10.1161/HYPERTENSIONAHA.108.189141
  3. Lee RE, Seligmann AW, Clark MA, Borhani NO, Queenan JT, O'Brien ME. Therapeutically refractory hypertension: causative factors, and medical management with chlorothiazide and other agents. Ann Intern Med 1958;49:1129-37. https://doi.org/10.7326/0003-4819-49-5-1129
  4. Leslie CH. A new antihypertensive drug (mebutamate) in the treatment of refractory hypertension in geriatric patients: preliminary report. J Am Geriatr Soc 1962;10:85-9. https://doi.org/10.1111/j.1532-5415.1962.tb00246.x
  5. Acelajado MC, Pisoni R, Dudenbostel T, et al. Refractory hypertension: definition, prevalence, and patient characteristics. J Clin Hypertens (Greenwich) 2012;14:7-12. https://doi.org/10.1111/j.1751-7176.2011.00556.x
  6. Gifford RW, Jr, Tarazi RC. Resistant hypertension: diagnosis and management. Ann Intern Med 1978;88:661-5. https://doi.org/10.7326/0003-4819-88-5-661
  7. Calhoun DA, Booth JN 3rd, Oparil S, et al. Refractory hypertension: determination of prevalence, risk factors, and comorbidities in a large, population-based cohort. Hypertension 2014;63:451-8. https://doi.org/10.1161/HYPERTENSIONAHA.113.02026
  8. Modolo R, de Faria AP, Sabbatini AR, Barbaro NR, Ritter AM, Moreno H. Refractory and resistant hypertension: characteristics and differences observed in a specialized clinic. J Am Soc Hypertens 2015;9:397-402. https://doi.org/10.1016/j.jash.2015.03.005
  9. Dudenbostel T, Acelajado MC, Pisoni R, Li P, Oparil S, Calhoun DA. Refractory hypertension: evidence of heightened sympathetic activity as a cause of antihypertensive treatment failure. Hypertension 2015;66:126-33. https://doi.org/10.1161/HYPERTENSIONAHA.115.05449
  10. Sim JJ, Bhandari SK, Shi J, et al. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system. Mayo Clin Proc 2013;88:1099-107. https://doi.org/10.1016/j.mayocp.2013.06.017
  11. de la Sierra A, Segura J, Banegas JR, et al. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension 2011;57:898-902. https://doi.org/10.1161/HYPERTENSIONAHA.110.168948
  12. Roberie DR, Elliott WJ. What is the prevalence of resistant hypertension in the United States? Curr Opin Cardiol 2012;27:386-91. https://doi.org/10.1097/HCO.0b013e328353ad6e
  13. Jung O, Gechter JL, Wunder C, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens 2013;31:766-74. https://doi.org/10.1097/HJH.0b013e32835e2286
  14. Egan BM, Zhao Y, Li J, 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 2013;62:691-7. https://doi.org/10.1161/HYPERTENSIONAHA.113.01448
  15. Grigoryan L, Pavlik VN, Hyman DJ. Patterns of nonadherence to antihypertensive therapy in primary care. J Clin Hypertens (Greenwich) 2013;15:107-11. https://doi.org/10.1111/jch.12030
  16. 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;124:1046-58. https://doi.org/10.1161/CIRCULATIONAHA.111.030189
  17. 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
  18. Irvin MR, Booth JN 3rd, Shimbo D, et al. Apparent treatmentresistant hypertension and risk for stroke, coronary heart disease, and all-cause mortality. J Am Soc Hypertens 2014;8:405-13. https://doi.org/10.1016/j.jash.2014.03.003
  19. Howard VJ, Cushman M, Pulley L, et al. The reasons for geographic and racial differences in stroke study: objectives and design. Neuroepidemiology 2005;25:135-43. https://doi.org/10.1159/000086678
  20. Muntner P, Davis BR, Cushman WC, et al. Treatment-resistant hypertension and the incidence of cardiovascular disease and endstage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 2014;64:1012-21. https://doi.org/10.1161/HYPERTENSIONAHA.114.03850
  21. Bangalore S, Fayyad R, Laskey R, et al. Prevalence, predictors, and outcomes in treatment-resistant hypertension in patients with coronary disease. Am J Med 2014;127:71-81.e1. https://doi.org/10.1016/j.amjmed.2013.07.038
  22. Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation 2012; 125:1635-42. https://doi.org/10.1161/CIRCULATIONAHA.111.068064
  23. Kumbhani DJ, Steg PG, Cannon CP, et al. Resistant hypertension: a frequent and ominous finding among hypertensive patients with atherothrombosis. Eur Heart J 2013;34:1204-14. https://doi.org/10.1093/eurheartj/ehs368
  24. Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension 2002; 39:982-8. https://doi.org/10.1161/01.HYP.0000016176.16042.2F
  25. Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann P. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002;40:892-6. https://doi.org/10.1161/01.HYP.0000040261.30455.B6
  26. 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;22:2217-26. https://doi.org/10.1097/00004872-200411000-00026
  27. Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch Intern Med 2008;168:1159-64. https://doi.org/10.1001/archinte.168.11.1159
  28. Sartori M, Calo LA, Mascagna V, et al. Aldosterone and refractory hypertension: a prospective cohort study. Am J Hypertens 2006; 19:373-9; discussion 380. https://doi.org/10.1016/j.amjhyper.2005.06.031
  29. Pimenta E, Gaddam KK, Oparil S, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension 2009;54:475-81. https://doi.org/10.1161/HYPERTENSIONAHA.109.131235
  30. Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 2005;85:679-715. https://doi.org/10.1152/physrev.00056.2003

Cited by

  1. Controlled Versus Uncontrolled Resistant Hypertension: Are They in the Same Bag? vol.20, pp.3, 2018, https://doi.org/10.1007/s11906-018-0825-7
  2. Resistant hypertension: a therapeutic challenge vol.20, pp.1, 2016, https://doi.org/10.1111/jch.13144
  3. Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus vol.20, pp.5, 2016, https://doi.org/10.1111/jch.13293
  4. Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial vol.19, pp.1, 2018, https://doi.org/10.1186/s13063-017-2343-3
  5. Resistant and refractory hypertension: two sides of the same disease? vol.41, pp.2, 2016, https://doi.org/10.1590/2175-8239-jbn-2018-0108
  6. Effect of exercise and physical activity on blood pressure in adults with resistant hypertension: a protocol for a systematic review vol.25, pp.2, 2016, https://doi.org/10.1080/10833196.2020.1728986
  7. Combination Antihypertensive Therapy Prescribing and Blood Pressure Control in a Real-World Setting vol.33, pp.4, 2020, https://doi.org/10.1093/ajh/hpz196
  8. Exercise: a therapeutic modality to treat blood pressure in resistant hypertension vol.25, pp.3, 2016, https://doi.org/10.1080/10833196.2020.1733781