What is the recommended approach for screening a patient for primary and secondary hypertension (HTN)?

Screening for Primary and Secondary Hypertension

Primary Hypertension Screening

All patients with confirmed hypertension should undergo basic screening with a 12-lead ECG, serum electrolytes, creatinine with eGFR, urinalysis with albumin-to-creatinine ratio, fasting glucose or HbA1c, lipid panel, and thyroid function tests. 1

Initial Assessment for All Hypertensive Patients

• Obtain a 12-lead ECG to assess for left ventricular hypertrophy, strain patterns, and arrhythmias in all patients with confirmed hypertension 1

• Basic laboratory panel should include:

  • Serum sodium and potassium (hypokalemia suggests primary aldosteronism) 1, 2
  • Serum creatinine and eGFR to assess renal function 1, 2
  • Urinalysis with microscopy looking for blood, protein, and casts 2, 3
  • Urinary albumin-to-creatinine ratio to detect early kidney damage 1, 2
  • Fasting blood glucose or HbA1c 2, 3
  • Fasting lipid panel 2, 3
  • Thyroid-stimulating hormone (TSH) 2, 3

• Cardiovascular risk stratification using SCORE2 or Pooled Cohort equations should guide treatment intensity 1

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Secondary Hypertension Screening

The 2024 ESC guidelines recommend measuring plasma aldosterone-to-renin ratio (ARR) in ALL adults with confirmed hypertension (Class IIa), representing a major departure from traditional selective screening approaches. 1, 2

Universal Screening Recommendation

• Plasma aldosterone-to-renin ratio (ARR) should be measured in all adults with confirmed hypertension, as primary aldosteronism affects 5-20% of hypertensive patients and most do not have hypokalemia 1, 2

• This represents a significant change from the 2017 ACC/AHA guidelines, which only recommended screening when specific clinical features were present 1

Mandatory Comprehensive Screening Scenarios

Young adults (<40 years) with hypertension require comprehensive screening for all major secondary causes (Class I recommendation), except those with obesity who should start with obstructive sleep apnea evaluation. 1

• Age of onset <30-40 years mandates full secondary hypertension workup 1, 2

• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive drugs including a diuretic) requires aggressive evaluation 1, 4

• Abrupt onset or sudden deterioration of previously controlled hypertension demands immediate investigation 1, 2, 5

• Hypertensive urgency or emergency necessitates screening for secondary causes 1, 2, 5

• Target organ damage disproportionate to duration or severity of hypertension 2, 5

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Targeted Screening Based on Clinical Clues

Primary Aldosteronism (Most Common Treatable Cause)

• Screen with ARR when ratio >20 with elevated aldosterone and suppressed renin 1, 2, 3

• Specific indications beyond universal screening include:

  • Spontaneous or substantial diuretic-induced hypokalemia 1, 2
  • Incidentally discovered adrenal mass 1
  • Family history of early-onset hypertension or stroke at young age (<40 years) 1

• Confirmatory testing with oral sodium loading test (24-hour urine aldosterone) or IV saline infusion test (plasma aldosterone at 4 hours) when ARR is positive 1, 3

• Localization studies with adrenal CT scan followed by adrenal vein sampling after biochemical confirmation 1, 3

Renovascular Disease

• Clinical clues requiring workup:

  • Abrupt onset or worsening hypertension 1, 2
  • Flash pulmonary edema 1, 2
  • Serum creatinine increase ≥50% within one week of starting ACE inhibitor or ARB 2, 3
  • Severe hypertension with unilateral smaller kidney or size difference >1.5 cm 3
  • Abdominal systolic-diastolic bruit on examination 3

• Initial imaging with renal Duplex Doppler ultrasound 2, 5

• Confirmatory imaging with CT or MRI renal angiography 2, 5

Obstructive Sleep Apnea

• Clinical presentation warranting evaluation:

  • Resistant hypertension with snoring, witnessed apneas, daytime sleepiness 2, 3
  • Obesity (BMI >30) with Mallampati class III-IV airway 3
  • Non-dipping or reverse-dipping nocturnal BP pattern on 24-hour ambulatory monitoring 2, 3

• Diagnostic testing with home sleep apnea testing or polysomnography 2, 5

Pheochromocytoma

• Clinical features requiring investigation:

  • Episodic symptoms (headaches, palpitations, sweating) 2, 3
  • Labile or paroxysmal hypertension 2, 3
  • Hypertensive crisis during anesthesia or surgery 3
  • Family history of pheochromocytoma or multiple endocrine neoplasia 3

• Screening tests: 24-hour urinary catecholamines or metanephrines, or plasma metanephrines 1, 2

• Imaging: Abdominal/adrenal CT or MRI after biochemical confirmation 2

Cushing Syndrome

• Physical examination findings suggesting diagnosis:
  • Central obesity with thin extremities, purple striae (not just obesity-related) 2, 3
  • Easy bruising, proximal muscle weakness 3
  • Moon facies, buffalo hump, supraclavicular fat pads 3

Renal Parenchymal Disease

• History suggesting diagnosis:

  • Urinary tract infections, obstruction, hematuria 1, 2
  • Urinary frequency and nocturia 1, 2
  • Family history of polycystic kidney disease 2

• Screening: Urinalysis with microscopy, urinary albumin-to-creatinine ratio, renal ultrasound 2, 5

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Critical Pitfalls to Avoid

• Do not perform expensive imaging (CT, MRI, angiography) before completing basic laboratory screening 2, 3

• Review all medications including over-the-counter drugs, herbals, and illicit substances that may cause or worsen hypertension before extensive workup 1, 2

• Recognize that ARR interpretation can be affected by medications: mineralocorticoid receptor antagonists raise aldosterone, while beta-blockers and direct renin inhibitors lower renin 2

• Refer to specialized hypertension centers when screening tests are positive and confirmatory testing is needed, or when surgical intervention is being considered 1, 5

• Understand that delayed diagnosis leads to vascular remodeling and residual hypertension even after treating the underlying cause 2, 5

• Secondary hypertension affects 5-10% of all hypertensive patients, increasing to 10-20% in resistant cases—maintain high index of suspicion 3, 5