A 52-year-old man with a 10-year history of hypertension presents to the clinic. His blood pressure is 168/104 mmHg despite being on amlodipine monotherapy. Which is the most common cause of resistant hypertension in this patient?

Explanation

## Most Common Cause of Resistant Hypertension **Key Point:** Resistant hypertension is defined as failure to achieve BP goal despite use of 3 or more antihypertensive agents at optimal doses, or need for 4+ agents to achieve control. The most common identifiable cause is **inadequate sodium restriction combined with medication non-adherence**, accounting for >50% of cases. ### Epidemiology of Resistant Hypertension Causes | Cause | Frequency | Mechanism | |-------|-----------|----------| | **Non-adherence + high sodium intake** | >50% | Reduced medication efficacy; sodium expansion of intravascular volume | | Primary aldosteronism | 5–10% | Mineralocorticoid excess; volume expansion | | Renovascular disease | 1–5% | Renin-angiotensin activation; unilateral renal artery stenosis | | Pheochromocytoma | <1% | Catecholamine excess; episodic BP surges | | Obstructive sleep apnea | 10–15% | Sympathetic activation; nocturnal BP elevation | | Chronic kidney disease | 10–20% | Sodium retention; reduced GFR | **Clinical Pearl:** Before attributing resistant hypertension to a secondary cause, always confirm: 1. Adherence to all 3+ agents (pill counts, pharmacy refill records) 2. Sodium intake <2.3 g/day (ask dietary history) 3. Absence of interfering drugs (NSAIDs, oral contraceptives, sympathomimetics, licorice) 4. Accurate BP measurement (home BP monitoring, exclude white-coat effect) **High-Yield:** The "Rule of Thirds" for resistant hypertension: - 1/3 due to non-adherence - 1/3 due to inadequate sodium restriction - 1/3 due to secondary causes or pseudoresistance ### Why Secondary Causes Are Rarer **Warning:** While primary aldosteronism, renovascular disease, and pheochromocytoma are important to screen for, they account for <15% of resistant hypertension cases combined. Jumping to expensive imaging (renal artery ultrasound, CT angiography, plasma free metanephrines) without first addressing adherence and sodium intake is wasteful and delays effective management. **Tip:** The diagnostic approach to resistant hypertension should follow a stepwise algorithm: 1. Verify diagnosis and exclude pseudoresistance 2. Optimize lifestyle (sodium restriction, weight loss, exercise) 3. Ensure adherence with simplified regimen 4. Add fourth agent (e.g., spironolactone for volume expansion) 5. Screen for secondary causes only if refractory despite above steps [cite:Harrison 21e Ch 246]