What is the recommended work-up for an older adult patient with resistant hypertension, considering their age, medical history, and current medication regimen?

Resistant Hypertension Work-Up

Initial Step: Exclude Pseudoresistance

Before pursuing an extensive work-up, approximately 50% of patients diagnosed with resistant hypertension actually have pseudoresistance rather than true resistant hypertension, making this the critical first step. 1

Confirm True Resistant Hypertension

• Verify proper blood pressure measurement technique using validated automated devices with appropriate cuff size, proper patient positioning, and averaging ≥2 readings on ≥2 occasions 1
• Rule out white coat hypertension with home blood pressure monitoring (≥135/85 mmHg confirms true hypertension) or 24-hour ambulatory monitoring (≥130/80 mmHg confirms true hypertension) 1
• Assess medication adherence as non-adherence is the most common cause of apparent treatment resistance 1
• Review current antihypertensive regimen to ensure optimal drug choices, appropriate doses (maximally tolerated), and inclusion of a diuretic 1
• Identify interfering substances including NSAIDs, decongestants, oral contraceptives, corticosteroids, cyclosporine, erythropoietin, cocaine, amphetamines, and certain dietary supplements 1

Basic Screening Work-Up

Once pseudoresistance is excluded, perform basic screening for secondary hypertension 1:

History and Physical Examination

• Age of onset (<30 years suggests secondary cause, especially without obesity, metabolic syndrome, or family history) 1
• Sudden deterioration in blood pressure control or hypertensive emergency 1
• Symptoms suggesting secondary causes: snoring/daytime somnolence (sleep apnea), muscle weakness/polyuria (primary aldosteronism), headaches/palpitations/sweating (pheochromocytoma), claudication (renovascular disease) 1
• Check for orthostatic hypotension (supine-to-standing decrease of ≥20 mmHg systolic or ≥10 mmHg diastolic) which occurs in ~7% of men over 70 and carries 64% increased mortality 1

Basic Laboratory Tests

• Serum electrolytes (sodium, potassium—hypokalemia suggests primary aldosteronism) 1
• Serum creatinine and eGFR (assess for renal parenchymal disease) 1
• Thyroid-stimulating hormone (TSH) 1
• Dipstick urinalysis (proteinuria suggests renal disease) 1

Further Diagnostic Testing

Additional investigations should be carefully chosen based on clinical clues from history, physical examination, and basic tests 1:

Common Secondary Causes to Screen For

The most common secondary causes in adults are renal parenchymal disease, renovascular hypertension, primary aldosteronism, chronic sleep apnea, and substance/drug-induced hypertension 1:

• Primary aldosteronism screening: Confirmatory testing (intravenous saline suppression test), adrenal CT imaging, adrenal vein sampling 1
• Renovascular hypertension: Renal artery imaging with duplex ultrasound, CT angiography, or MR angiography depending on renal function 1
• Renal parenchymal disease: Kidney ultrasound 1
• Obstructive sleep apnea: Sleep study if clinically suspected 1
• Pheochromocytoma: Abdominal/pelvic CT or MRI, plasma/urine metanephrines 1
• Cushing's syndrome: Dexamethasone suppression test 1

Optimize Medical Therapy Before Extensive Testing

Before pursuing expensive secondary cause investigations, optimize the current treatment regimen 1:

Diuretic Optimization

• Use thiazide-like diuretics (chlorthalidone, indapamide) rather than thiazides (hydrochlorothiazide) for superior efficacy 1
• Switch to loop diuretics for eGFR <30 mL/min/1.73m² or clinical volume overload 1
• Ensure maximally tolerated diuretic doses as occult volume overload underlies most treatment resistance 1

Add Fourth-Line Agent

• Add low-dose spironolactone (25-50 mg daily) as the preferred fourth-line agent if serum potassium <4.5 mmol/L and eGFR >45 mL/min/1.73m² 1, 2
• Alternative fourth-line agents if spironolactone contraindicated: amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 1

Specialist Referral Indications

Consider referral to a hypertension specialist for 1:

• Blood pressure remaining uncontrolled despite four-drug therapy at optimal doses
• Multiple drug intolerances
• Suspected secondary hypertension requiring specialized diagnostic testing
• Need for access to appropriate expertise and resources for resistant hypertension management

Critical Pitfalls to Avoid

• Do not pursue extensive secondary cause work-up before excluding pseudoresistance and optimizing medical therapy 1
• Do not overlook medication adherence as the most common cause of apparent resistance 1
• Do not fail to include an appropriate diuretic in the regimen, as this is essential for resistant hypertension management 1, 3
• Do not delay lifestyle modifications including sodium restriction <2 g/day, weight loss, DASH diet, regular exercise, and alcohol limitation 1