6.3 Resistant Hypertension

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Resistant hypertension is defined as high blood pressure that remains uncontrolled in a patent treated with three or more antihypertensive medications at optimal (or maximally tolerated) doses including a diuretic and after excluding pseudo-resistance as well as the substance/drug-induced hypertension and secondary hypertension. Resistant hypertension affects around 10% of hypertensives. A diagnosis of true resistant hypertension should be made only after a thorough assessment to exclude apparent or pseudo-resistant hypertension. Almost 50% of patients diagnosed with resistant hypertension have pseudo-resistance rather than true resistant hypertension19.

Causes of pseudo-resistant hypertension:

  • Improper blood pressure measurement
  • Heavily calcified or arteriosclerotic arteries that are difficult to compress (in elderly persons)
  • White-coat effect
  • Side effects of medication
  • Poor doctor patient relation
  • Inadequate patient education
  • Memory or psychiatric problems
  • Antihypertensive medication issues such as inadequate doses, inappropriate

combinations, poor patient adherence, complicated dosing schedules and physician inertia (failure to change or increase dose regimens when not at goal)

Typical characteristics of patients with resistant hypertension

  • Old age, especially >75 years
  • High baseline blood pressure and chronicity of uncontrolled hypertension
  • Target organ damage
  • Diabetes
  • Obesity
  • Atherosclerotic vascular disease
  • Aortic stiffening
  • Women
  • Excessive dietary salt

Factors contributing to resistant hypertension

A. Lifestyle factors

  • Inadequate physical activity
  • Excess alcohol intake
  • Excess dietary salt
  • Cocaine and amphetamines misuse (e.g., yaba)

B. Drug related causes

  • Non-steroidal anti-inflammatory drugs
  • Contraceptive hormones
  • Adrenal steroid hormones
  • Sympathomimetic agents (nasal decongestants, diet pills)
  • Erythropoeitin, cyclosporin, and tacrolimus
  • Liquorice (suppresses the metabolism of cortisol)
  • Herbal supplements (ephedra, bitter orange, etc.)

C. Volume overload

  • Progressive renal insufficiency
  • High salt intake
  • Inadequate diuretic therapy

Secondary causes of resistant hypertension

  • Primary hyperaldosteronism
  • Renal artery stenosis
  • Renal parenchymal disease
  • Obstructive sleep apnoea
  • Phaeochromocytoma – (Episodic palpitations, headaches, sweating)
  • Thyroid diseases
  • Cushing's syndrome
  • Coarctation of the aorta
  • Intracranial tumors

Treatment of Resistant Hypertension

Non-pharmacologic intervention

All non-pharmacological interventions mentioned in the chapter on management of hypertension should be implemented vigorously.

Pharmacologic intervention

Use of low dose Spironolactone (25 mg once daily, increasing to 50 mg once daily) as the preferred fourth agent if the blood potassium concentration is less than 4.5 mmol/L. If Spironolactone causes painful gynecomastia then Amiloride or Eplerenone can be considered as a substitute. Centrally acting agonist (Methyldopa and Clonidine) or direct vasodilators (Hydralazine or Minoxidil) are further options. With direct vasodilators, concomitant high-dose beta-blockers (Metoprolol or Bisoprolol or Nebivolol) and loop diuretics (Furosemide) will be needed to counteract reflex tachycardia and edema. Combined alpha- and beta-blockers (Labetalol and Carvedilol) may improve blood pressure control. Whatever the final combination of treatments, a patient with resistant hypertension is likely to be receiving at least four antihypertensive drugs daily.

Device therapy

Interest is growing in device therapy for resistant hypertension, with the objective of improving blood pressure control without resorting to further medication. Two techniques have recently been evaluated: percutaneous transluminal radiofrequency sympathetic denervation of the renal arteries and carotid baroreflex activation.