What is the initial step in the workup for resistant hypertension?

Workup for Resistant Hypertension

The initial step in evaluating resistant hypertension is to perform 24-hour ambulatory blood pressure monitoring to exclude pseudoresistance (particularly white-coat hypertension, which accounts for approximately 50% of apparent resistant cases), followed immediately by verification of medication adherence and assessment of interfering substances. 1, 2

Step 1: Confirm True Treatment Resistance

Before proceeding with any workup, you must verify the patient meets criteria for resistant hypertension:

• Blood pressure remains >130/80 mmHg despite adherence to 3 antihypertensive medications at maximal or maximally tolerated doses, specifically: a renin-angiotensin system blocker (ACE inhibitor or ARB), a long-acting calcium channel blocker, and an appropriate diuretic 1, 2

• Perform 24-hour ambulatory BP monitoring (gold standard) to exclude white-coat hypertension—this is critical as approximately 50% of apparent resistant cases are pseudoresistant 1, 2

• If ambulatory monitoring is unavailable, use home BP monitoring as an alternative 1

Step 2: Verify Medication Adherence and Exclude Interfering Substances

Medication nonadherence accounts for roughly half of treatment resistance, making this assessment essential 3:

• Direct questioning about medication-taking behavior 3
• Pill counts or pharmacy refill records 3
• Consider supervised medication administration if adherence remains uncertain 1

Screen for and discontinue interfering substances 1:

• NSAIDs (most common culprit) 3
• Oral contraceptives 3
• Stimulants (decongestants, amphetamines, cocaine) 1
• Certain antidepressants (SNRIs, MAOIs) 3
• Excessive alcohol intake (>2 drinks/day for men, >1 for women) 3
• Licorice, herbal supplements (ephedra, ma huang) 1

Step 3: Optimize Current Antihypertensive Regimen

Before pursuing extensive secondary hypertension workup, ensure the regimen is optimized 1:

• Verify appropriate diuretic selection: Switch from hydrochlorothiazide to thiazide-like diuretics (chlorthalidone or indapamide), which are significantly more effective 1, 3

• Use loop diuretics if eGFR <30 mL/min/1.73m² or clinical volume overload is present, as thiazides become ineffective at lower GFR 1, 3

• Confirm sodium intake <2400 mg/day, as excessive sodium is a major contributor to treatment resistance 1, 3

Step 4: Screen for Secondary Causes of Hypertension

Basic screening should be performed in all patients with resistant hypertension 1, 2:

Initial Laboratory Assessment:

• Serum electrolytes (sodium, potassium) 1
• eGFR and serum creatinine 1
• TSH (thyroid dysfunction) 1
• Urinalysis with dipstick for proteinuria 1
• Aldosterone-to-renin ratio to screen for primary aldosteronism, even with normal potassium levels 3, 2

Clinical Screening:

• Obstructive sleep apnea: Use Berlin Questionnaire or Epworth Sleepiness Score; confirm with polysomnography if suspected 1, 2
• Renal artery stenosis: Consider in patients with sudden BP deterioration, flash pulmonary edema, or unexplained renal dysfunction 1, 3
• Chronic kidney disease: Assess baseline eGFR 1, 3

Further Investigations (Based on Clinical Suspicion):

• Primary aldosteronism: Confirmatory testing (saline suppression test), adrenal CT imaging, adrenal vein sampling 1
• Renovascular disease: Renal artery duplex ultrasound, CT or MR angiography 1
• Pheochromocytoma: 24-hour urinary metanephrines, plasma metanephrines 1
• Cushing syndrome: 24-hour urinary free cortisol, dexamethasone suppression test 1

Step 5: Assess for Target Organ Damage

Systematic evaluation for hypertension-mediated organ damage is essential 1, 2:

• Ocular: Funduscopic examination for hypertensive retinopathy 1
• Cardiac: ECG and echocardiogram for left ventricular hypertrophy, assess for coronary artery disease 1
• Renal: Proteinuria assessment, eGFR calculation 1
• Peripheral vascular: Ankle-brachial index 1

Step 6: Maximize Lifestyle Interventions

While conducting the workup, reinforce lifestyle modifications 1, 3:

• Sodium restriction to <2400 mg/day (most critical) 1, 3
• Weight loss if BMI >25 kg/m² 1, 3
• Regular aerobic exercise (≥150 minutes/week moderate intensity) 1, 3
• Limit alcohol (≤2 drinks/day for men, ≤1 for women) 1, 3
• Ensure ≥6 hours uninterrupted sleep 1

Common Pitfalls to Avoid

• Failing to perform ambulatory BP monitoring: This is the single most important initial step, as white-coat hypertension is extremely common in this population 1, 2

• Continuing hydrochlorothiazide instead of switching to chlorthalidone or indapamide: Thiazide-like diuretics are significantly more effective 1, 3

• Pursuing extensive secondary hypertension workup before confirming true resistance and optimizing the regimen: This wastes resources and delays effective treatment 1

• Using inappropriate diuretic for kidney function: Thiazides are ineffective when eGFR <30 mL/min/1.73m²; switch to loop diuretics 1, 3

• Overlooking medication nonadherence: Directly address this before assuming treatment failure 1, 3

When to Refer to a Hypertension Specialist

Consider specialist referral if 1, 2:

• BP remains uncontrolled (>130/80 mmHg) after 6 months of optimized treatment 2
• A specific secondary cause is suspected requiring specialized testing 1, 2
• Patient requires 4 or more medications to achieve control 2
• Complications arise (severe hyperkalemia, progressive renal dysfunction) 3