What is the workup for resistant hypertension?

Workup for Resistant Hypertension

The workup for resistant hypertension must first confirm true resistance by excluding pseudoresistance through ambulatory blood pressure monitoring and medication adherence verification, followed by systematic screening for secondary causes—particularly primary aldosteronism, obstructive sleep apnea, and chronic kidney disease—while documenting target-organ damage. 1, 2

Step 1: Confirm True Resistant Hypertension

Before proceeding with an extensive workup, you must rule out pseudoresistance:

• Perform 24-hour ambulatory blood pressure monitoring to exclude white coat hypertension, which accounts for approximately 50% of apparent resistant cases 2
• Verify medication adherence through direct questioning, pill counts, or pharmacy records—nonadherence is a leading cause of apparent resistance 1, 2
• Ensure proper BP measurement technique with appropriate cuff size and correct patient positioning to avoid falsely elevated readings 1
• Confirm the patient is on ≥3 antihypertensive agents from different classes at optimal doses, including a diuretic, with BP remaining >140/90 mmHg (or >130/80 mmHg in patients with diabetes or chronic kidney disease) 1

Step 2: Screen for Secondary Causes of Hypertension

Resistant hypertension is almost always multifactorial, and secondary causes are common. Screen systematically for the following conditions: 1

Primary Aldosteronism (Most Common)

• Obtain aldosterone-to-renin ratio as the primary screening test—primary aldosteronism affects 17-23% of resistant hypertension cases 3
• Look for hypokalemia and metabolic alkalosis, though these are late manifestations and may be absent in early disease 3
• If positive, refer for confirmatory testing and adrenal imaging 3

Obstructive Sleep Apnea

• Screen all patients for snoring, witnessed apnea, and excessive daytime sleepiness 1
• Consider polysomnography if clinical suspicion is high—sleep apnea is extremely common in resistant hypertension 1

Chronic Kidney Disease

• Check serum creatinine and calculate eGFR—CKD with creatinine clearance <30 mL/min is a major contributor to resistance 1
• Assess for proteinuria 1

Renal Artery Stenosis

• Consider in young females or patients with known atherosclerotic disease, especially if there is worsening renal function after starting ACE inhibitors or ARBs 1
• Duplex ultrasound, MRA, or CT angiography can be used, though MRA has high sensitivity but lower specificity 1

Pheochromocytoma

• Screen with 24-hour urine metanephrines if patient has episodic hypertension, palpitations, diaphoresis, or headache 3
• This represents only 0.1-0.6% of resistant hypertension cases but is critical not to miss 3

Cushing's Syndrome

• Screen with 24-hour urine cortisol if patient has moon facies, central obesity, abdominal striae, or interscapular fat deposition 1, 3

Aortic Coarctation

• Check for differential in brachial or femoral pulses and listen for systolic bruit 1

Step 3: Identify Contributing Lifestyle and Medication Factors

• Review all medications and substances that may interfere with BP control, including NSAIDs, decongestants, oral contraceptives, corticosteroids, and herbal supplements 1, 4
• Assess dietary sodium intake—excessive sodium is a major contributor to resistance 1
• Evaluate for obesity—older age and obesity are the strongest risk factors for resistant hypertension 1
• Screen for excessive alcohol consumption 5

Step 4: Document Target-Organ Damage

Target-organ damage supports the diagnosis of poorly controlled hypertension and influences treatment goals:

• Assess for retinopathy through fundoscopic examination 1
• Evaluate for left ventricular hypertrophy with ECG or echocardiography 1
• Document chronic kidney disease as noted above—this establishes a BP goal of 130/80 mmHg 1
• Screen for atherosclerotic disease given the high cardiovascular risk in this population 1

Step 5: Consider Specialist Referral

• Refer to a hypertension specialist if BP remains elevated despite 6 months of treatment in the absence of suspected secondary causes 1
• Refer to appropriate specialists (endocrinology, nephrology, sleep medicine) if specific secondary causes are identified 1
• Retrospective studies show that hypertension specialists achieve BP control in 52-53% of patients with resistant hypertension 1

Common Pitfalls to Avoid

• Do not proceed with extensive secondary cause workup without first confirming true resistance through ambulatory monitoring and adherence verification—this wastes resources and delays appropriate treatment 2
• Do not overlook medication optimization before labeling hypertension as resistant—ensure the regimen includes a long-acting dihydropyridine calcium channel blocker, RAS blocker, and thiazide-like diuretic (chlorthalidone or indapamide preferred) at maximal tolerated doses 2, 4
• Do not forget to check potassium and renal function before and after adding mineralocorticoid receptor antagonists, as hyperkalemia is a significant risk 2