What is the mechanism and management of secondary hypertension?

Mechanisms and Management of Secondary Hypertension

Secondary hypertension accounts for approximately 10% of all hypertension cases and is characterized by an identifiable underlying cause that can potentially be treated or cured, leading to improved blood pressure control and reduced cardiovascular risk. 1

Mechanisms of Secondary Hypertension

Secondary hypertension can arise from various pathophysiological mechanisms depending on the underlying cause:

Common Causes and Mechanisms

1. Primary Aldosteronism

   • Mechanism: Excessive aldosterone production leading to sodium retention, potassium excretion, and volume expansion
   • Clinical indicators: Resistant hypertension, hypokalemia (spontaneous or diuretic-induced), incidentally discovered adrenal mass 1, 2

2. Renovascular Disease

   • Mechanism: Renal artery stenosis activates the renin-angiotensin-aldosterone system, causing vasoconstriction and sodium retention
   • Types: Atherosclerotic (older adults) or fibromuscular dysplasia (younger patients, especially women) 2

3. Renal Parenchymal Disease

   • Mechanism: Impaired sodium excretion, volume expansion, and increased renin-angiotensin-aldosterone system activity
   • Features: Abnormal urinalysis, elevated creatinine, reduced eGFR 1, 2

4. Obstructive Sleep Apnea

   • Mechanism: Intermittent hypoxia, sympathetic activation, and endothelial dysfunction
   • Features: Snoring, daytime somnolence, obesity, resistant hypertension 2

5. Medication/Substance-Induced

   • Mechanism: Various pathways including sympathetic activation, sodium retention, and direct vasoconstriction
   • Common agents: NSAIDs, oral contraceptives, sympathomimetics, corticosteroids, immunosuppressants, alcohol, illicit drugs 1, 2

6. Endocrine Disorders

   • Pheochromocytoma: Catecholamine excess causing vasoconstriction
   • Cushing's syndrome: Cortisol excess leading to mineralocorticoid effects
   • Thyroid disorders: Altered cardiac output and peripheral vascular resistance 2

Clinical Indicators for Secondary Hypertension Screening

Screening is recommended when these indicators are present:

• Early onset hypertension (especially <30 years)
• Severe or resistant hypertension (BP >140/90 mmHg despite three optimal-dose medications including a diuretic)
• Sudden deterioration in previously controlled BP
• Target organ damage disproportionate to hypertension duration
• Specific clinical features (hypokalemia, abdominal bruits, etc.)
• Hypertensive urgency or emergency 1, 2

Diagnostic Approach

Initial Screening Tests

• Complete blood count, electrolytes, creatinine, eGFR, fasting glucose, lipid profile
• Urinalysis and urinary albumin-to-creatinine ratio
• 12-lead ECG 2

Specific Testing Based on Suspected Cause

1. Primary Aldosteronism

   • Plasma aldosterone-to-renin activity ratio (ARR) 1, 2

2. Renovascular Disease

   • Renal Duplex Doppler ultrasound
   • CT or MR angiography in selected cases 2

3. Renal Parenchymal Disease

   • Renal ultrasound
   • Urine protein quantification 2

4. Obstructive Sleep Apnea

   • Screening questionnaires (Berlin, Epworth)
   • Overnight oximetry or polysomnography 2

5. Endocrine Disorders

   • Specific hormonal tests based on clinical suspicion 2

Management Approach

General Principles

1. Target the underlying cause whenever possible:

   • Adrenalectomy for unilateral primary aldosteronism
   • Mineralocorticoid receptor antagonists for bilateral primary aldosteronism
   • Renal angioplasty for fibromuscular dysplasia
   • Medical therapy for atherosclerotic renal artery stenosis
   • CPAP for obstructive sleep apnea
   • Discontinuation of offending medications 2

2. Optimize antihypertensive therapy while addressing the underlying cause:

   • ACE inhibitors or ARBs (contraindicated in bilateral renal artery stenosis)
   • Calcium channel blockers
   • Diuretics
   • Beta-blockers
   • Mineralocorticoid receptor antagonists 1

Management of Resistant Hypertension

1. Optimize current regimen:

   • Maximize diuretic therapy
   • Use loop diuretics for eGFR <30 ml/min/1.73m² 2

2. Add fourth-line agents:

   • Spironolactone (first choice)
   • Amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 2

3. Consider specialist referral for complex cases requiring multidisciplinary management 2

Important Considerations and Pitfalls

• Residual hypertension: Even after treating the secondary cause, BP may not normalize completely due to vascular remodeling or concomitant essential hypertension 3

• Medication monitoring: Watch for hyperkalemia with ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists, especially in renal impairment 2

• Avoid common errors:

  • Failing to screen appropriate patients
  • Continuing medications that contribute to hypertension
  • Inadequate diuretic dosing
  • Not referring complex cases to specialists 2

• Early detection is crucial: Prompt diagnosis and treatment minimize irreversible vascular changes and target organ damage 3

By systematically evaluating patients with suspected secondary hypertension and implementing targeted treatment strategies, clinicians can significantly improve blood pressure control and reduce cardiovascular risk in this population.