Abstract
Resistant hypertension is a common medical problem. It carries a significantly increased risk of end-organ damage and cardiovascular events compared with more easily controlled hypertension. Resistant hypertension is most often related to isolated systolic hypertension and is characterized by aldosterone excess and increased intravascular volume. Its diagnosis requires the exclusion of pseudoresistance. The etiology of resistant hypertension is almost always multifactorial. Common reversible contributing factors need to be identified and addressed. Secondary causes of hypertension, such as primary aldosteronism, parenchymal and vascular kidney disease, and obstructive sleep apnea, require investigation and effective treatment if present. Therapy for resistant hypertension should be based on use of rational drug class combinations at optimal doses, with particular attention to adequate diuretic use. The addition of an aldosterone antagonist may further improve blood pressure control.
Similar content being viewed by others
References and Recommended Reading
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. Circulation 2008, 117:e510–e526.
Chobanian AV, Bakris GL, Black HR, et al.: Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003, 42:1206–1252.
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, 4:393–404.
Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al.: A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The international verapamil-trandolapril study (INVEST): a randomized controlled trial. JAMA 2003, 290:2805–2816.
Cuspidi C, Macca G, Sampieri L, et al.: High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens 2001, 19:2063–2070.
Lewington S, Clarke R, Qizilbash N, et al.: Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002, 360:1903–1913.
Salles GF, Cardoso CR, Muxfeldt ES: Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med 2008, 168:2340–2346.
Muxfeldt ES, Cardoso CR, Salles GF: Prognostic value of nocturnal blood pressure reduction in resistant hypertension. Arch Intern Med 2009, 169:874–880.
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg [no authors listed]. JAMA 1967, 202:1028–1034.
Lloyd-Jones DM, Evans JC, Larson MG, et al.: Differential control of systolic and diastolic blood pressure: factors associated with lack of blood pressure control in the community. Hypertension 2000, 36:594–599.
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, 168:1159–1164.
Gonzaga CC, Calhoun DA: Resistant hypertension and hyperaldosteronism. Curr Hypertens Rep 2008, 10:496–503.
Moser M, Setaro JF: Clinical practice. Resistant or difficult-to-control hypertension. N Engl J Med 2006, 355:385–392.
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, 18:1422–1428.
Singer GM, Izhar M, Black HR: Goal-oriented hypertension management: translating clinical trials to practice. Hypertension 2002, 40:464–469.
Oliveria SA, Lapuerta P, McCarthy BD, et al.: Physicianrelated barriers to the effective management of uncontrolled hypertension. Arch Intern Med 2002, 162:413–420.
Boudville N, Ward S, Benaroia M, House AA: Increased sodium intake correlates with greater use of antihypertensive agents by subjects with chronic kidney disease. Am J Hypertens 2005, 18:1300–1305.
Ashley FW Jr, Kannel WB: Relation of weight change to changes in atherogenic traits: the Framingham study. J Chronic Dis 1974, 27:103–114.
Modan M, Almog S, Fuchs Z, et al.: Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Hypertension 1991, 17:565–573.
Mosso L, Carvajal C, Gonzalez A, et al.: Primary aldosteronism and hypertensive disease. Hypertension 2003, 42:161–165.
Calhoun DA, Nishizaka MK, Zaman MA, et al.: Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002, 40:892–896.
Campese VM, Mitra N, Sandee D: Hypertension in renal parenchymal disease: why is it so resistant to treatment? Kidney Int 2006, 69:967–973.
Levey AS, Coresh J, Balk E, et al.: National kidney foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med 2003, 139:137–147.
Casas JP, Chua W, Loukogeorgakis S, et al.: Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005, 366:2026–2033.
Grote L, Hedner J, Peter JH: Sleep-related breathing disorder is an independent risk factor for uncontrolled hypertension. J Hypertens 2000, 18:679–685.
Lavie P, Hoffstein V: Sleep apnea syndrome: a possible contributing factor to resistant. Sleep 2001, 24:721–725.
Logan AG, Perlikowski SM, Mente A, et al.: High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens 2001, 19:2271–2277.
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, 131:453–459.
Robinson GV, Stradling JR, Davies RJ: Sleep. 6: Obstructive sleep apnoea/hypopnoea syndrome and hypertension. Thorax 2004, 59:1089–1094.
Lenders JW, Eisenhofer G, Mannelli M, Pacak K: Phaeochromocytoma. Lancet 2005, 366:665–675.
Garg JP, Elliott WJ, Folker A, et al.: Resistant hypertension revisited: a comparison of two university-based cohorts. Am J Hypertens 2005, 18:619–626.
Hermida RC, Ayala DE, Fernandez JR, Calvo C: Chronotherapy improves blood pressure control and reverts the nondipper pattern in patients with resistant hypertension. Hypertension 2008, 51:69–76.
Jamerson K, Weber MA, Bakris GL, et al.: Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008, 359:2417–2428.
Ernst ME, Carter BL, Goerdt CJ, et al.: Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 2006, 47:352–358.
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the antihypertensive and lipidlowering treatment to prevent heart attack trial (ALLHAT). JAMA 2002, 288:2981–2997.
Nishizaka MK, Zaman MA, Calhoun DA: Efficacy of lowdose spironolactone in subjects with resistant hypertension. Am J Hypertens 2003, 16:925–930.
Eide IK, Torjesen PA, Drolsum A, et al.: Low-renin status in therapy-resistant hypertension: a clue to efficient treatment. J Hypertens 2004, 22:2217–2226.
Townsend RR, DiPette DJ, Goodman R, et al.: Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients. Clin Pharmacol Ther 1990, 48:665–675.
Rodilla E, Costa JA, Perez-Lahiguera F, et al.: Spironolactone and doxazosin treatment in patients with resistant hypertension. Rev Esp Cardiol 2009, 62:158–166.
Stergiou GS, Makris T, Papavasiliou M, et al.: Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy. J Hypertens 2005, 23:883–889.
Yusuf S, Teo KK, Pogue J, et al.: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008, 358:1547–1559.
Mann JF, Schmieder RE, McQueen M, et al.: Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 2008, 372:547–553.
Oparil S, Yarows SA, Patel S, et al.: Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial. Lancet 2007, 370:221–229.
Krum H, Schlaich M, Whitbourn R, et al.: Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 2009, 373:1275–1281.
Illig KA, Levy M, Sanchez L, et al.: An implantable carotid sinus stimulator for drug-resistant hypertension: Surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg 2006, 44:1213–1218.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pisoni, R., Ahmed, M.I. & Calhoun, D.A. Characterization and treatment of resistant hypertension. Curr Cardiol Rep 11, 407–413 (2009). https://doi.org/10.1007/s11886-009-0059-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11886-009-0059-z