What is the workup for resistant hypertension?

Workup for Resistant Hypertension

The workup for resistant hypertension begins with confirming true treatment resistance using 24-hour ambulatory blood pressure monitoring to exclude pseudoresistance (white-coat effect and medication nonadherence), followed by systematic screening for secondary causes and assessment of target organ damage. 1, 2

Step 1: Confirm True Treatment Resistance

Before proceeding with an extensive workup, you must first verify that the patient actually has resistant hypertension:

• Confirm the patient is taking 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 a diuretic 1, 2
• Blood pressure remains >130/80 mmHg on this regimen 1, 2
• Perform 24-hour ambulatory blood pressure monitoring as the gold standard to exclude white-coat hypertension, which accounts for approximately 50% of apparent resistant cases 1, 3, 4
• If ambulatory monitoring is unavailable, use home blood pressure monitoring as an alternative 1, 3
• Verify medication adherence through direct questioning, pill counts, or pharmacy records 3, 5
• Ensure proper BP measurement technique using appropriate cuff size and correct patient positioning 3, 5

Step 2: Exclude Reversible Contributing Factors

Before pursuing secondary causes, identify and address common reversible factors:

• Assess sodium intake - confirm dietary sodium is <2400 mg/day 1, 3
• Review all medications for agents that elevate blood pressure: NSAIDs, decongestants, oral contraceptives, sympathomimetics, adrenal steroids, and VEGF pathway inhibitors 6, 7
• Evaluate lifestyle factors: obesity, excessive alcohol intake (>2 drinks/day for men, >1 drink/day for women), lack of physical activity 1, 3
• Verify appropriate diuretic type for kidney function - thiazide-like diuretics (chlorthalidone or indapamide) maintain efficacy down to eGFR 30 mL/min/1.73m²; switch to loop diuretics if eGFR <30 mL/min/1.73m² 1, 3

Step 3: Screen for Secondary Causes

Primary Aldosteronism:

• Screen ALL patients with resistant hypertension using aldosterone-to-renin ratio, even with normal potassium levels 2, 3
• A high ratio (generally 20-30 when aldosterone in ng/dL and renin activity in ng/mL/h) suggests primary aldosteronism 2
• This is particularly important in young patients (<30 years) 3

Obstructive Sleep Apnea:

• Evaluate using Berlin Questionnaire or Epworth Sleepiness Score 3
• Confirm with polysomnography if suspected 3
• This is a very common but underdiagnosed cause of resistant hypertension 7

Renal Disease:

• Assess baseline eGFR and screen for renal parenchymal disease 3
• Screen for renal artery stenosis with kidney ultrasound, followed by renal artery imaging (CT angiography or MR angiography) if clinically indicated 3, 7

Endocrine Disorders:

• Check TSH to evaluate for hypothyroidism or hyperthyroidism 1, 3
• Consider screening for Cushing's syndrome, pheochromocytoma, and hyperparathyroidism if clinical features suggest these diagnoses 1, 7

Step 4: Assess for Target Organ Damage

Perform systematic evaluation for hypertension-mediated organ damage, which supports the diagnosis of poorly controlled hypertension and influences treatment goals: 1, 2

• Ocular: funduscopic examination for hypertensive retinopathy 1
• Cardiac: assess for left ventricular hypertrophy (ECG and/or echocardiography) and coronary artery disease 1, 2
• Renal: check for proteinuria and reduced glomerular filtration rate 1, 2
• Peripheral vascular: measure ankle-brachial index to assess for peripheral arterial disease 1

Step 5: Consider Specialist Referral

Refer to a hypertension specialist (nephrologist, cardiologist, or endocrinologist) if: 1, 2

• Blood pressure remains uncontrolled after 6 months of treatment 1
• A specific secondary cause of hypertension is suspected 1, 2
• The patient requires 4 or more medications to achieve control (controlled resistant hypertension) 1

Studies demonstrate that referral to hypertension specialists improves outcomes, with control rates increasing from 18% to 52-53% at 1-year follow-up 1

Common Pitfalls to Avoid

• Do not skip ambulatory or home blood pressure monitoring - approximately 50% of apparent resistant hypertension is actually white-coat effect 1, 3, 4
• Do not assume medication adherence - directly verify through multiple methods 3, 5
• Do not overlook volume overload - this is a common but unappreciated cause of treatment resistance that responds to appropriate diuretic therapy 1, 6
• Do not fail to screen for primary aldosteronism - this is recommended in ALL patients with resistant hypertension, not just those with hypokalemia 2, 3
• Do not use standard thiazides when thiazide-like diuretics (chlorthalidone or indapamide) are available, as the latter are superior for resistant hypertension 3, 5