What causes accelerated hypertension?

What Causes Accelerated Hypertension

Accelerated hypertension is primarily caused by severe or poorly treated essential hypertension, with secondary causes including smoking, Black race, renal disease, and primary aldosteronism being significant contributors. 1

Primary Underlying Mechanism

The fundamental pathophysiology involves breakdown of vascular autoregulation from continuous exposure to extremely high blood pressure levels, leading to characteristic vascular damage with myointimal proliferation and fibrinoid necrosis. 1 The severity of this proliferative vascular response directly parallels both the severity and duration of blood pressure elevation. 1

Most Common Causes

Essential Hypertension (Most Frequent)

• Severe or poorly treated essential hypertension is the most common harbinger of accelerated/malignant phase hypertension. 1
• The condition has become less prevalent due to earlier treatment initiation and more efficient therapeutic programs. 1

Modifiable Risk Factors

• Smoking: A large proportion of patients with accelerated hypertension are current smokers. 1
• Race: Black individuals are more frequently affected than Caucasians. 1
• Excessive dietary sodium: Contributes through direct blood pressure elevation and blunting of antihypertensive medication effects, particularly in salt-sensitive populations (elderly, African Americans, chronic kidney disease patients). 1
• Heavy alcohol intake: Associated with treatment-resistant hypertension; cessation can reduce systolic blood pressure by 7.2 mmHg and diastolic by 6.6 mmHg. 1

Secondary Causes (Often Underestimated)

Renal Causes

• Chronic kidney disease: Poorly controlled hypertension accelerates progression to organ failure. 2, 3
• Renovascular hypertension: Second most common cause of secondary hypertension, representing approximately 2% of adult hypertension cases. 4
• Mechanisms include reduced functioning nephrons, sodium retention, volume expansion, and upregulated renin-angiotensin-aldosterone system. 3

Endocrine Causes

• Primary aldosteronism: Causes 1-11% of primary hypertension cases and is the most frequent cause of secondary hypertension overall. 4, 5
• Pheochromocytoma: Produces catecholamines causing hypertension in approximately 70% of cases (stable or paroxysmal). 4
• Cushing syndrome: Glucocorticoid excess causes vascular and smooth muscle abnormalities. 6, 7
• Thyroid disease: Affects smooth muscle function and contributes to motility disorders. 6, 7

Obstructive Sleep Apnea

• 83% of patients with treatment-resistant hypertension have unsuspected sleep apnea (apnea-hypopnea index ≥10 events/hour). 1
• Mechanisms include intermittent hypoxemia inducing sustained sympathetic nervous system activation, increased reactive oxygen species, and reduced nitric oxide bioavailability. 1

Drug-Induced Causes

Common Offending Agents

• NSAIDs: Increase blood pressure by 3/1 mmHg with nonselective agents; can antagonize RAAS-inhibitors and beta-blockers. 1
• Anticancer drugs: Vascular endothelial growth factor inhibitors increase blood pressure in 80-90% of patients; tyrosine kinase inhibitors and proteasome inhibitors also elevate blood pressure. 1
• Corticosteroids, calcineurin inhibitors, sympathomimetics (pseudoephedrine, cocaine, amphetamines). 1
• Antidepressants: SNRIs increase blood pressure by 2/1 mmHg; tricyclics have 3.19 odds ratio for hypertension. 1
• Recreational drugs: Amphetamines, LSD, cocaine, ecstasy can precipitate hypertensive emergencies. 1

Clinical Pitfalls

The presence of secondary causes is often underestimated in clinical practice. 1 Clinicians should maintain high suspicion for:

• Patients with severe hypertension (≥180/110 mmHg) where primary aldosteronism prevalence reaches 13%. 1
• Economically deprived populations where malignant hypertension is more frequently observed. 1
• Patients requiring fundoscopy to detect retinal hemorrhages, exudates, and papilledema (accelerated hypertension is diagnosed when these findings occur without papilledema). 1