What testing is needed for a patient with resistant hypertension to check for primary aldosteronism, renal stenosis, and sleep disorders?

Testing for Resistant Hypertension: Primary Aldosteronism, Renal Stenosis, and Sleep Apnea

For a patient with resistant hypertension, you should order: (1) plasma aldosterone-to-renin ratio (ARR) for primary aldosteronism screening, (2) renal Doppler ultrasound or CT/MRI angiography for renal artery stenosis, and (3) overnight polysomnography for obstructive sleep apnea. 1

Primary Aldosteronism Screening

When to Screen

• Screen all patients with resistant hypertension - primary aldosteronism occurs in 11-20% of resistant hypertension cases 1, 2
• Additional screening indications include spontaneous or diuretic-induced hypokalemia, incidentally discovered adrenal mass, family history of early-onset hypertension, or stroke before age 40 1, 2

The Screening Test

• Order plasma aldosterone-to-renin ratio (ARR) as the screening test of choice 1, 2
• The most commonly used cutoff is ARR >30 (when aldosterone in ng/dL and renin activity in ng/mL/h) 2
• Alternative cutoff of ARR >100 ng/dL per ng/mL/h has been validated in some studies 3

Critical Medication Considerations

You can perform ARR testing without stopping current medications - the 2024 ESC Guidelines explicitly support two pragmatic approaches 1:

1. Preferred approach: Test without medication changes for efficiency, then interpret results in context of current medications 1
2. Alternative approach: Optimize medications before testing for "clean" results 1

Medication effects on ARR you must know 1:

• Beta-blockers, NSAIDs, alpha-2 agonists, and steroids cause false-positive results (suppress renin more than aldosterone) 1
• ACE inhibitors, ARBs, and diuretics cause false-negative results (increase renin) 1
• Calcium channel blockers have minimal effect and are preferred if medication adjustment is chosen 1

Important Pre-Test Considerations

• Correct hypokalemia before testing - low potassium suppresses aldosterone production and causes false-negatives 4
• Review prior potassium levels - spontaneous hypokalemia increases likelihood of primary aldosteronism 1

Next Steps After Positive Screening

• Refer to hypertension specialist or endocrinologist for confirmatory testing (saline suppression test or oral salt loading) 1, 2
• Confirmatory testing and adrenal vein sampling are required to distinguish unilateral (surgical) from bilateral (medical) disease 2, 4

Renal Artery Stenosis Evaluation

Screening Tests

Order renal Doppler ultrasound as first-line imaging 1

• If Doppler is inconclusive or high clinical suspicion, proceed to abdominal CT angiography or MRI 1

When to Suspect Renal Artery Stenosis

• Age <40 years (suggests fibromuscular dysplasia) 1
• Age >60 years with acute change in blood pressure or flash pulmonary edema (suggests atherosclerotic disease) 1
• Acute decline in kidney function after starting ACE inhibitor or ARB 5
• Resistant hypertension with unexplained kidney dysfunction 1

Management Expectations

• Medical therapy is first-line treatment for atherosclerotic renal artery stenosis 1
• Revascularization (angioplasty ± stenting) may be reasonable only if medical management fails or for fibromuscular dysplasia 1

Obstructive Sleep Apnea Assessment

When to Order Sleep Study

Order overnight polysomnography for all patients with resistant hypertension - up to 60% have obstructive sleep apnea (OSA) 1

Clinical Clues Suggesting OSA

• Non-dipping or reverse-dipping pattern on 24-hour ambulatory blood pressure monitoring 1
• Obesity 1
• Symptoms of snoring, witnessed apneas, excessive daytime sleepiness, morning headaches 1

Important Caveat

• Lack of suggestive symptoms does not rule out OSA - many patients are asymptomatic 1
• Validated questionnaires (STOP-BANG, Epworth Sleepiness Scale) may help identify high-risk patients but should not replace polysomnography in resistant hypertension 1

Diagnostic Criteria

• Apnea-hypopnea index (AHI) >5 confirms diagnosis 1
• Severity classification: mild (AHI <15), moderate (AHI 15-30), severe (AHI >30) 1

Additional Workup Considerations

Before Declaring True Resistant Hypertension

• Exclude pseudo-resistance first 1:
  • Confirm poor adherence through careful questioning or objective drug monitoring 1
  • Rule out white-coat hypertension with ambulatory or home blood pressure monitoring 1
  • Ensure proper blood pressure measurement technique 1
  • Verify adequate diuretic therapy (loop diuretic if eGFR <30 mL/min/1.73 m²) 1

Other Secondary Causes to Consider

• Check plasma creatinine, eGFR, and urinalysis for renal parenchymal disease 1
• Consider 24-hour urinary or plasma metanephrines if paroxysmal symptoms suggest pheochromocytoma 1
• Review medication list for drugs that elevate blood pressure (NSAIDs, decongestants, steroids, oral contraceptives) 1

Common Pitfalls to Avoid

1. Don't delay ARR testing due to medication concerns - testing on current medications is acceptable and preferred by recent guidelines 1
2. Don't assume normal potassium rules out primary aldosteronism - over 50% of patients have normal potassium 2, 5
3. Don't skip sleep study in asymptomatic patients - OSA is highly prevalent and often asymptomatic in resistant hypertension 1
4. Don't order renal angiography expecting revascularization to cure hypertension - medical therapy remains primary treatment for most renal artery stenosis 1
5. Don't forget to refer positive ARR results - confirmatory testing and subtype determination require specialized expertise 1, 2