When should we investigate for secondary hypertension?

When to Investigate for Secondary Hypertension

Secondary hypertension should be investigated in patients with early onset hypertension (<30 years), resistant hypertension, sudden deterioration in BP control, hypertensive urgency/emergency, or when strong clinical clues suggest a secondary cause. 1

Key Clinical Scenarios Requiring Investigation

• Early onset hypertension (<30 years of age), particularly in the absence of typical risk factors such as obesity, metabolic syndrome, or family history 1, 2

• Resistant hypertension (BP uncontrolled despite optimal doses of ≥3 antihypertensive medications from different classes, including a diuretic) 1, 2

• Sudden deterioration in previously well-controlled BP or abrupt onset of hypertension 1, 2

• Hypertensive urgency or emergency situations requiring immediate intervention 1

• Target organ damage disproportionate to the duration or severity of hypertension 1, 2

• Specific clinical features suggesting secondary causes (see below) 1, 2

Clinical Clues by Specific Secondary Causes

Renal Parenchymal Disease

• History of urinary tract infections, obstruction, hematuria 2
• Abnormal urinalysis (proteinuria, hematuria) 1
• Elevated serum creatinine 1

Renovascular Disease

• Abdominal/flank bruits 1, 3
• Flash pulmonary edema 2
• Acute kidney injury following ACE inhibitor or ARB initiation (>50% increase in creatinine) 4
• Asymmetric kidney sizes (>1.5 cm difference) 4

Primary Aldosteronism

• Spontaneous or diuretic-induced hypokalemia 1, 2
• Muscle cramps or weakness 2
• Incidentally discovered adrenal mass 1
• Family history of early-onset hypertension 1

Obstructive Sleep Apnea

• Snoring, witnessed apneas, daytime somnolence 2
• Obesity, large neck circumference 2
• Non-dipping nocturnal BP pattern 2

Pheochromocytoma

• Episodic headaches, sweating, palpitations 2
• Labile hypertension 3
• Orthostatic hypotension 1

Initial Screening Approach

1. Basic screening for all suspected cases should include:

   • Thorough history and physical examination 1
   • Basic blood biochemistry (sodium, potassium, eGFR) 1
   • TSH measurement 1
   • Urinalysis 1

2. Further targeted investigations based on clinical suspicion:

   • Plasma aldosterone-to-renin ratio for suspected primary aldosteronism 1
   • Renal ultrasound for suspected renovascular disease or renal parenchymal disease 1
   • Sleep studies for suspected obstructive sleep apnea 1
   • Specialized hormonal tests for suspected endocrine causes 1

Important Considerations

• Secondary hypertension affects approximately 5-10% of all hypertensive patients 1, 4, 5

• Early diagnosis and treatment can potentially cure hypertension or significantly improve BP control, reducing cardiovascular risk 1, 6

• Investigation for secondary causes should generally be preceded by exclusion of pseudoresistant hypertension (poor medication adherence, white coat effect) and drug/substance-induced hypertension 1, 7

• Referral to a specialist center is recommended for further investigation and management of suspected secondary hypertension, particularly for complex cases 1, 5

• Despite appropriate treatment of secondary causes, blood pressure rarely returns completely to normal with long-term follow-up, suggesting either concomitant essential hypertension or irreversible vascular remodeling 6