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Definition, risk factors, and evaluation of resistant hypertension

David A Calhoun, MD
Raymond R Townsend, MD
Section Editors
George L Bakris, MD
Norman M Kaplan, MD
Deputy Editor
John P Forman, MD, MSc


Patients with persistent hypertension despite multiple medications are at high risk for adverse cardiovascular events and are more likely than those with controlled hypertension to have a secondary (ie, identifiable) cause, which is usually at least in part reversible.

The definition, prevalence, risk factors, and evaluation of resistant hypertension will be reviewed here. Specific causes of secondary hypertension will be briefly mentioned. The treatment and prognosis of resistant hypertension, indications for referral to a hypertension specialist, and how one identifies patients who should be screened for secondary hypertension are discussed elsewhere. (See "Treatment of resistant hypertension" and "Evaluation of secondary hypertension".)


Resistant hypertension — Resistant hypertension is defined in the 2008 American Heart Association scientific statement and the 2013 guidelines from the European Societies of Hypertension and Cardiology (ESH/ESC) as blood pressure that remains above goal in spite of concurrent use of three antihypertensive agents of different classes [1,2]. Thus, patients whose blood pressure is controlled with four or more medications should be considered to have resistant hypertension.

If tolerated, one of the three agents should be a diuretic, and all agents should be prescribed at optimal doses (ie, 50 percent or more of the maximum recommended antihypertensive dose) [1]. Goal blood pressure is less than 140/90 mmHg in average-risk hypertensive patients. There is evidence supporting a lower goal blood pressure in patients with atherosclerotic cardiovascular disease, stroke, diabetes mellitus, or chronic kidney disease. The supportive data are presented separately. (See "What is goal blood pressure in the treatment of hypertension?" and "Goal blood pressure in patients with cardiovascular disease or at high risk", section on 'Goal blood pressure' and "Antihypertensive therapy to prevent recurrent stroke or transient ischemic attack" and "Treatment of hypertension in patients with diabetes mellitus", section on 'Goal blood pressure' and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Blood pressure goal'.)

Although patients with resistant hypertension may have elevations in both systolic and diastolic pressures, isolated systolic hypertension is common. In the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) of over 33,000 hypertensive patients treated with different antihypertensive drugs, only 67 percent of participants attained a systolic blood pressure below 140 mmHg, whereas 92 percent attained a diastolic pressure below 90 mmHg [3]. Treatment of older adults with isolated systolic hypertension that is resistant to therapy may be more difficult since intensification of the therapeutic regimen may lead to unacceptably low diastolic pressures. (See "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension", section on 'Resistant hypertension' and "Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension".)


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Literature review current through: Sep 2016. | This topic last updated: Jun 13, 2016.
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  1. 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.
  2. Mancia G, Fagard R, Narkiewicz K, 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; 31:1281.
  3. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich) 2002; 4:393.
  4. Dudenbostel T, Siddiqui M, Oparil S, Calhoun DA. Refractory Hypertension: A Novel Phenotype of Antihypertensive Treatment Failure. Hypertension 2016; 67:1085.
  5. Dudenbostel T, Acelajado MC, Pisoni R, et al. Refractory Hypertension: Evidence of Heightened Sympathetic Activity as a Cause of Antihypertensive Treatment Failure. Hypertension 2015; 66:126.
  6. 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. Calhoun DA. Apparent and true resistant hypertension: why not the same? J Am Soc Hypertens 2013; 7:509.
  8. 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; 7:471.
  9. Jung O, Gechter JL, Wunder C, et al. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J Hypertens 2013; 31:766.
  10. Tomaszewski M, White C, Patel P, et al. High rates of non-adherence to antihypertensive treatment revealed by high-performance liquid chromatography-tandem mass spectrometry (HP LC-MS/MS) urine analysis. Heart 2014; 100:855.
  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.
  12. Muxfeldt ES, Bloch KV, Nogueira Ada R, Salles GF. True resistant hypertension: is it possible to be recognized in the office? Am J Hypertens 2005; 18:1534.
  13. Redon J, Campos C, Narciso ML, et al. Prognostic value of ambulatory blood pressure monitoring in refractory hypertension: a prospective study. Hypertension 1998; 31:712.
  14. de la Sierra A, Banegas JR, Oliveras A, et al. Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs. J Hypertens 2012; 30:1211.
  15. Pierdomenico SD, Lapenna D, Bucci A, et al. Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension. Am J Hypertens 2005; 18:1422.
  16. Persell SD. Prevalence of resistant hypertension in the United States, 2003-2008. Hypertension 2011; 57:1076.
  17. Muxfeldt ES, Nogueira Ada R, Salles GF, Bloch KV. Demographic and clinical characteristics of hypertensive patients in the internal medicine outpatient clinic of a university hospital in Rio de Janeiro. Sao Paulo Med J 2004; 122:87.
  18. 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.
  19. Egan BM, Zhao Y, Rehman SU, et al. Treatment resistant hypertension in a community-based practice network (abstract). J Clin Hypertens (Greenwich) 2009; OR-12:A6.
  20. Daugherty SL, Powers JD, Magid DJ, et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation 2012; 125:1635.
  21. Ma J, Lee KV, Stafford RS. Changes in antihypertensive prescribing during US outpatient visits for uncomplicated hypertension between 1993 and 2004. Hypertension 2006; 48:846.
  22. Berlowitz DR, Ash AS, Hickey EC, et al. Inadequate management of blood pressure in a hypertensive population. N Engl J Med 1998; 339:1957.
  23. Amar J, Chamontin B, Genes N, et al. Why is hypertension so frequently uncontrolled in secondary prevention? J Hypertens 2003; 21:1199.
  24. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens 2014; 32:3.
  25. 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.
  26. Chan CC, Reid CM, Aw TJ, et al. Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis. J Hypertens 2009; 27:2332.
  27. Mancia G, De Backer G, Dominiczak A, et al. 2007 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 2007; 25:1105.
  28. Setaro JF, Black HR. Refractory hypertension. N Engl J Med 1992; 327:543.
  29. Fugh-Berman A. Herb-drug interactions. Lancet 2000; 355:134.
  30. Licht CM, de Geus EJ, Seldenrijk A, et al. Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension. Hypertension 2009; 53:631.
  31. 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.
  32. Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension 2002; 39:982.
  33. Azizi M, Sapoval M, Gosse P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet 2015; 385:1957.
  34. Stergiou GS, Myers MG, Reid JL, et al. Setting-up a blood pressure and vascular protection clinic: requirements of the European Society of Hypertension. J Hypertens 2010; 28:1780.
  35. Douma S, Petidis K, Doumas M, et al. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet 2008; 371:1921.
  36. Calhoun DA, Nishizaka MK, Zaman MA, et al. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40:892.
  37. Eide IK, Torjesen PA, Drolsum A, et al. Low-renin status in therapy-resistant hypertension: a clue to efficient treatment. J Hypertens 2004; 22:2217.
  38. Gonçalves SC, Martinez D, Gus M, et al. Obstructive sleep apnea and resistant hypertension: a case-control study. Chest 2007; 132:1858.
  39. Logan AG, Perlikowski SM, Mente A, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens 2001; 19:2271.
  40. Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL, et al. Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 2007; 131:453.
  41. Parati G, Lombardi C, Hedner J, et al. Recommendations for the management of patients with obstructive sleep apnoea and hypertension. Eur Respir J 2013; 41:523.
  42. Mejia AD, Egan BM, Schork NJ, Zweifler AJ. Artefacts in measurement of blood pressure and lack of target organ involvement in the assessment of patients with treatment-resistant hypertension. Ann Intern Med 1990; 112:270.
  43. Mancia G, Parati G, Pomidossi G, et al. Alerting reaction and rise in blood pressure during measurement by physician and nurse. Hypertension 1987; 9:209.