What are the treatment approaches for various mechanisms in secondary hypertension?

Treatment Approaches for Various Mechanisms in Secondary Hypertension

Treatment of secondary hypertension should target the underlying cause while simultaneously controlling blood pressure, with specific approaches tailored to each mechanism to reduce morbidity and mortality. 1

Identifying Secondary Hypertension

Secondary hypertension affects 5-10% of hypertensive patients, but prevalence increases to approximately 20% in resistant hypertension cases 2, 1.

Clinical indicators requiring screening include:

• Early onset hypertension (<30 years of age)
• Resistant hypertension (BP >140/90 mmHg despite 3 optimal-dose medications including a diuretic)
• Sudden deterioration in previously controlled BP
• Hypertensive urgency or emergency
• Target organ damage disproportionate to hypertension duration/severity 1

Treatment Approaches by Specific Mechanism

1. Primary Aldosteronism

• Diagnostic clues: Unprovoked hypokalemia, resistant hypertension
• Treatment:
  • Unilateral disease: Adrenalectomy is treatment of choice 2, 1
  • Bilateral disease: Mineralocorticoid receptor antagonists:
    • Spironolactone (50-100 mg daily, can be titrated up to 300-400 mg)
    • Eplerenone (less potent but fewer side effects) 1, 3
  • Monitor serum potassium before initiating therapy, within first week, at one month, and periodically thereafter 3

2. Renovascular Hypertension

• Diagnostic clues: Abdominal bruits, resistant hypertension, deteriorating renal function
• Treatment:
  • Fibromuscular dysplasia: Percutaneous transluminal renal angioplasty without stenting 1
  • Atherosclerotic renal artery stenosis: Medical therapy is preferred when renal function is preserved 2, 1
    • ACE inhibitors/ARBs (with caution in bilateral disease)
    • Calcium channel blockers
    • Diuretics
    • Statins and antiplatelet therapy
  • Revascularization may be considered for refractory hypertension despite three-drug regimen or progressive decline in renal function 1

3. Obstructive Sleep Apnea

• Diagnostic clues: Snoring, daytime sleepiness, obesity
• Treatment:
  • Weight loss (if applicable)
  • Continuous positive airway pressure (CPAP) therapy 2, 1
  • Mandibular advancement devices
  • Standard antihypertensive therapy as needed

4. Drug/Substance-Induced Hypertension

• Diagnostic clues: Temporal relationship between medication use and BP elevation
• Treatment:
  • Discontinue or reduce offending agents when possible (NSAIDs, oral contraceptives, sympathomimetics, corticosteroids, erythropoietin, cyclosporine, tacrolimus) 1
  • If medication cannot be discontinued, add appropriate antihypertensive therapy
  • Beta-blockers (not metoprolol) should be used for drug-induced tachycardia (antidepressant, anti-psychotic drugs) 2

Management of Resistant Hypertension

For patients with resistant hypertension after excluding secondary causes:

1. Optimize current regimen:

   • Maximize diuretic therapy (thiazide-like preferred over thiazide diuretics)
   • Use loop diuretics for eGFR <30 ml/min/1.73m² 2, 1

2. Add fourth-line agent:

   • Spironolactone (if serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m²)
   • If spironolactone is contraindicated: amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 2, 1

3. Consider referral to specialized centers for:

   • Renal denervation for uncontrolled BP despite optimal medical therapy
   • Complex cases requiring multidisciplinary management 2, 1

Important Considerations and Pitfalls

1. Always exclude pseudoresistance before diagnosing resistant hypertension:

   • Poor BP measurement technique
   • White coat effect
   • Medication nonadherence
   • Suboptimal medication choices 2

2. Monitor for complications:

   • Hyperkalemia with ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists
   • Renal function deterioration with ACE inhibitors/ARBs, especially in renovascular disease 3, 4

3. Avoid common errors:

   • Failing to screen appropriate patients for secondary causes
   • Continuing medications that contribute to hypertension
   • Inadequate dosing of diuretics in volume-dependent hypertension
   • Not referring complex cases to specialists when appropriate 1

By targeting the specific underlying mechanism while maintaining adequate blood pressure control, treatment of secondary hypertension can significantly improve outcomes and potentially cure hypertension in select patients.