resistant hypertension; refractory hypertension

Introduction

blood pressure that remains above goal despite treatment with optimal doses of 3 antihypertensives of different classes, including a diuretic (also see secondary hypertension) or uncontrolled blood pressure on >= 4 drugs

Etiology

• primary hyperaldosteronism (22% of patients with resistant hypertension)
• renovascular hypertension (renal artery stenosis)
• chronic kidney disease (ESRD)
• pheochromocytoma
• obstructive sleep apnea (up to 83%)
• medication non-compliance
• consumption of substances that aggravate hypertension
  • dietary salt
  • excessive alcoholic beverage
  • nonsteroidal anti-inflammatory drugs
  • licorice
  • decongestants
    • pseudoephedrine
    • phenylephrine

Epidemiology

• 20% of patients with chronic hypertension

Laboratory

• plasma aldosterone/plasma renin activity
• serum K+: hypokalemia inconsistently associated with primary hyperaldosteronism
• angiotensin-2 in plasma
• captopril-renin stimulation test
• plasma free metanephrines &/or 24 hour urine metanephrines

Diagnostic procedures

• ambulatory blood pressure monitoring (distinguishes from white-coat hypertension)
• renal ultrasound for renal artery stenosis
• sleep study (polysomnography) for obstructive sleep apnea

* note BP goals for ambulatory blood pressure may differ from those of office blood pressure

Complications

• disease interaction(s) of primary hyperaldosteronism, chronic renal failure & resistant hypertension
• disease interaction(s) of obstructive sleep apnea with resistant hypertension

Differential diagnosis

• white-coat hypertension (1/3 of cases)
• secondary hypertension

Management

• see treatment of chronic hypertension
  • patient presumably on ACE inhibitor or ARB, calcium channel blocker & a thiazide diuretic or loop diuretic
  • if patient not on diuretic, prescribe one unless ESRD
• general
  • confirm out-of-office BP measurement
  • life-style modifications
    • low sodium diet (< 2400 mg/day)
    • achieve ideal body weight
    • ensure adequate sleep hygiene, at least 6 hours/night[15]
    • aerobic exercise reduces 24-hour & daytime ambulatory blood pressure & office systolic systolic blood pressure
  • discontinue offending medications include OTC
  • correct underlying cause(s)
• pharmaceuticals
  • addition of antihypertensive of a new class may be of benefit
  • consider switching HCTZ to chlorthalidone or indapamide
    • chlorthalidone more effective than hydrochlorothiazide
    • switch thiazide diuretic to loop diuretic if eGFR < 20 mL/min
  • mineralocorticoid receptor antagonist if hyperaldosteronism
    • spironolactone as add on
    • spironolactone not inferior to clonidine & it is QD
      • inferior to renal artery angioplasty with fibromuscular dysplasia
• renal sympathetic denervation
  • renal denervation device in the SYMPLICITY HTN-3 trial failed to lower systolic BP by > 10 mm Hg
  • of no benefit
• arterial-venous Coupler device that mechanically lowers systolic blood pressure via AV anastomosis shows promise

Notes

• 29% of patients claiming complete adherence to therapy showed a marked blood pressure response when treatment was observed

More general terms

• chronic hypertension