What causes malignant hypertension?

Causes of Malignant Hypertension

Malignant hypertension is primarily caused by the breakdown of vascular autoregulation resulting from continuous exposure to extremely high blood pressure levels, leading to pathological changes including myointimal proliferation and fibrinoid necrosis of small arteries and arterioles. 1

Primary Causes

• Severe or poorly treated essential hypertension: The most common underlying cause of malignant hypertension 1
• Secondary causes of hypertension: Often underestimated in prevalence 1
• Prolonged exposure to high blood pressure: The severity of vascular damage correlates with both the level and duration of blood pressure elevation 1

Risk Factors and Contributing Conditions

Patient-Related Factors

• Smoking: A large number of patients with malignant hypertension are current smokers 1
• Race: Black individuals are more frequently affected than Caucasians 1
• Medication non-adherence: The most common precipitating factor for malignant hypertension 2
• Socioeconomic factors: More commonly observed in economically deprived populations 1

Secondary Causes

1. Pharmacological triggers:

   • Anticancer drugs, particularly vascular endothelial growth factor inhibitors (80-90% risk) 1
   • Tyrosine kinase inhibitors and proteasome inhibitors 1
   • Immunosuppressant medications 2
   • Recreational drugs (amphetamines, LSD, cocaine, ecstasy) 1
   • Other medications (see below)

2. Endocrine disorders:

   • Pheochromocytoma 1
   • Cushing's syndrome 1
   • Thyroid disease 1
   • Hyperparathyroidism 1
   • Acromegaly 1

3. Renal disorders:

   • Renal artery stenosis
   • Glomerulonephritis
   • Renal parenchymal disease

4. Genetic causes:

   • Liddle's syndrome 1
   • Glucocorticoid-remediable aldosteronism 1

5. Other conditions:

   • Aortic coarctation 1
   • Excessive licorice consumption 1
   • Severe pre-eclampsia or eclampsia 1

Pathophysiological Mechanisms

The pathogenesis of malignant hypertension involves:

1. Vascular damage:

   • Myointimal proliferation and fibrinoid necrosis of small arteries 1
   • Spasm and forced dilatation of small arterioles 1
   • Leakage of fluid into extracellular space causing small hemorrhages 1

2. Immune system activation: Recent evidence suggests the immune system plays an important role in the development of malignant hypertension 3

3. Renin-angiotensin-aldosterone system activation: Well-established contributor to pathogenesis 3

4. Endothelial dysfunction: Key factor in development of vascular damage 3

5. Systemic microvascular damage: Affects multiple organ systems including retina, brain, heart, and kidneys 4

Clinical Implications

Malignant hypertension represents a true medical emergency with:

• Mortality rate of >79% at one year if untreated 5
• Median survival of only 10.4 months without treatment 5
• High risk of permanent target organ damage affecting:
  • Brain (hypertensive encephalopathy)
  • Heart (left ventricular failure)
  • Kidneys (acute deterioration in renal function)
  • Eyes (retinopathy with flame hemorrhages, cotton wool spots, papilledema)
  • Vascular system (disseminated intravascular coagulation)

The prevalence of malignant hypertension has decreased due to earlier treatment of hypertension and more efficient therapeutic programs 1, 5, but the absolute number of new cases has remained relatively stable in recent decades 3.

Prevention and Management

Early recognition and aggressive management are essential, with the goal of bringing diastolic blood pressure down to 100-110 mmHg over 24 hours 1. Treatment should focus on both controlling blood pressure and addressing any underlying causes.