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Separating resistant hypertension from hypertension

Separating resistant hypertension from hypertension

True resistant hypertension is uncommon in general practice.

It is defined as persistent elevation of blood pressure above 140/90–150/95 mmHg in patients who are adhering to a triple-drug regimen including a diuretic, with all three drugs prescribed at maximum recommended and tolerated doses for at least 3 months.1

For older patients (>70 years of age) with isolated systolic hypertension, resistant hypertension is defined as failure of an adequate triple-drug regimen to bring systolic blood pressure down to below 160 mmHg.2

Scenarios that suggest resistant hypertension

  • False high blood pressure should be excluded first; it includes:

-Cuff hypertension, due to the use of an inappropriately small cuff size

-Office (white coat) hypertension: when a patient’s blood pressure is raised in the clinic setting (first reading). Around 15-20% of patients diagnosed with hypertension actually have normal blood pressure at home or on ambulatory blood pressure monitoring. (Masked hypertension is the opposite phenomenon: a normal blood pressure reading in the clinic but ambulatory or home blood pressure readings in the hypertensive range) 

-Pseudo-hypertension, seen in elderly patients (>70 years of age) with atherosclerotic arteries, and a calcified brachial artery. The cuff pressure is inappropriately high compared with the intra-arterial pressure

  • True high blood pressure

-Inappropriate drug therapy is the most common cause of resistant hypertension. This can be either an incorrect drug combination (for example, using drugs from the same pharmaceutical group) or inadequate dosing (for example, using a short-acting preparation once daily)3

-Poor compliance with treatment (approximately half of all patients discontinue antihypertensive therapy within 1 year or receive irregular treatment) and lifestyle modification (patients are encouraged to reduce their salt intake and their alcohol consumption, take steps to reduce their weight and to reduce their exposure to stress)4,5

-Ingestion of a substance that elevates blood pressure,6 for example, non-steroidal anti-inflammatory drugs, oral contraceptives, glucocorticoids, mineralocorticoids, sympathomimetics (nasal decongestants, appetite suppressants), liquorice, phenothiazines, antidepressants, cyclosporine, MAO inhibitors, tyramine-rich foods, erythropoietin, cocaine

-Obstructive sleep apnoea

  • True resistant hypertension

(a) Extracellular volume expansion7

-Inadequate diuretic therapy
-Renal insufficiency
-Therapy with direct arterial vasodilators
-Excessive sodium intake

(b) Secondary hypertension

Management of resistant hypertension

  • Measure blood pressure according to guidelines. False high blood pressure readings should be excluded. Review vasopressor medications and drug therapy for appropriateness of drug dose and combinations. Salt restriction, weight reduction and stress management are essential.
  • Rule out white coat hypertension by measurement of blood pressure at home or by ambulatory monitoring.
  • Treat obstructive sleep apnoea, if present.
  • Persistent volume expansion (even without oedema) contributes to resistant hypertension. Effective diuretic (loop diuretic) use is almost always necessary to achieve blood pressure control.8
  • Add low dose spironolactone (25 mg daily) to multidrug treatment regimens.8
  • If these measures fail, consider taking the opinion of a specialist or hospitalising the patient.
  • Renal denervation by catheter-based radiofrequency ablation of the renal sympathetic nerves lowers the blood pressure in patients with resistant hypertension.

Flow diagram to show the steps to diagnose and treat resistant hypertension. Source M. Mohsen Ibrahim, 201311



  1. Fagard RH. Resistant Hypertension. Heart 2012;98:254–261.
  2. The 6th report of the joint national committee on prevention detection, evaluation and treatment of high blood pressure. Arch Intern Med 1997;157:2413–2446.
  3. Parker MG. Resistant Hypertension. Am J Kidney Dis 2008:52:796–802.
  4. Yiannakopoulou ECh, et al. Adherence to antihypertensive treatment: a critical factor for blood pressure control. Eur J Cardiovasc Prev Rehabil 2005;12:243–249.
  5. Vrijens B, et al. Adherence to prescribed antihypertensive drug treatments: longitudinal study of electronically compiled dosing histories. BMJ 2008,336:1114–1117.
  6. The 7th report of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure NIH publication NO 04-8230. August 2004, pages 59–60.
  7. Gaddam KK, et al. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch Intern Med 2008;168:1159–1164.
  8. Nishizaka Mk, et al. Efficacy of low-dose spironolactone in subjects with resistant hypertension. Am J Hypertens 2003;16:925–930.
  9. Krum H, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicenter safety and proof-of-principle cohort study. Lancet 2009;373:1275–1281.
  10. Simplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011;57:911–917.
  11. Mosen Ibrahim M. Egyptian Hypertension Society President’s message, December 2013. Available from: www:// Accessed January 2016.

Adapted from: The Egyptian Hypertension Society: EGYPTIAN HYPERTENSION GUIDELINES.

Omar Salah Awwad

Professor of Cardiology
Department of Cardiology
Ain Shams University
resistant hypertension