What is the best approach to manage a patient with uncontrolled hypertension, considering their past medical history, demographic information, and potential underlying causes such as kidney disease or sleep apnea?

Management of Uncontrolled Hypertension: A Systematic Approach

For a patient with uncontrolled hypertension, you must first confirm true hypertension using proper measurement technique and exclude pseudoresistance (medication non-adherence and white coat effect), then systematically screen for secondary causes based on clinical clues, while simultaneously initiating or optimizing pharmacologic therapy with lifestyle modifications. 1

Step 1: Confirm True Uncontrolled Hypertension

Proper Blood Pressure Measurement

• Have the patient sit quietly with back supported for 5 minutes before measurement 1
• Use correct cuff size with air bladder encircling at least 80% of the arm (adult large cuff for most patients) 1
• Support arm at heart level, take minimum 2 readings at 1-minute intervals, and average them 1
• Measure BP in both arms; use the arm with higher readings for future measurements 1
• Check orthostatic BP (decline >20 mmHg systolic or >10 mmHg diastolic after 1 minute standing is abnormal) 1

Exclude Pseudoresistance

• Obtain home BP readings or 24-hour ambulatory BP monitoring to exclude white coat hypertension 1
• Directly assess medication adherence in a non-judgmental manner, discussing adverse effects, out-of-pocket costs, and dosing inconvenience 1
• Family members often provide more objective adherence assessments 1

Step 2: Identify Clinical Clues for Secondary Hypertension

High-Risk Features Requiring Secondary Hypertension Workup

• Age of onset <30 years (especially before puberty) 1, 2
• Resistant hypertension: BP >140/90 mmHg on ≥3 optimal-dose medications including a diuretic, OR BP controlled but requiring ≥4 medications 1
• Abrupt onset or sudden worsening of previously controlled BP 1, 3
• Severe or accelerated/malignant hypertension 1, 3
• Target organ damage disproportionate to duration/severity of hypertension 3

Specific Secondary Cause Clues from History

• Obstructive sleep apnea (25-50% of resistant hypertension): Snoring, witnessed apnea, excessive daytime sleepiness, non-restorative sleep 1, 3, 4
• Primary aldosteronism (8-20% of resistant hypertension): Unprovoked or diuretic-induced hypokalemia, muscle cramps/weakness 1, 3, 4
• Renovascular disease: Flash pulmonary edema, known atherosclerotic disease, worsening renal function after starting ACE inhibitor/ARB, increase in creatinine ≥50% within one week of starting RAS blocker 1, 3, 2
• Pheochromocytoma: Episodic hypertension with headache, palpitations, diaphoresis, pallor 1, 4
• Cushing syndrome: Weight gain, moon facies, central obesity, purple abdominal striae, buffalo hump, easy bruising 1
• Renal parenchymal disease: History of UTIs, obstruction, hematuria, frequent urination, nocturia, family history of polycystic kidney disease 1, 3, 4
• Medication/substance-induced: NSAIDs, oral contraceptives, decongestants, cocaine, amphetamines, steroids, alcohol 1, 4

Physical Examination Findings

• Coarctation of aorta (in patients ≤30 years): Lower thigh BP than arm BP, delayed/absent femoral pulses, differential in brachial/femoral pulses, systolic bruit 1
• Cushing syndrome: Truncal obesity, facial rounding, interscapular fat deposition 1
• Thyroid disease: Palpable thyroid gland enlargement 1
• Renal disease: Enlarged kidneys on palpation, abdominal masses, abdominal bruits 1

Step 3: Initial Laboratory and Diagnostic Workup

Basic Testing for ALL Patients with Newly Diagnosed or Uncontrolled Hypertension

• Fasting blood glucose (or comprehensive metabolic panel) 1
• Hemoglobin A1C (to detect pre-diabetes/early diabetes even with normal fasting glucose) 1
• Complete blood count 1
• Lipid profile 1
• Serum creatinine with estimated GFR 1
• Serum sodium, potassium, calcium 1
• Thyroid-stimulating hormone 1
• Urinalysis 1
• Electrocardiogram 1

Optional Tests for Target Organ Damage Assessment

• Echocardiogram 1
• Urinary albumin-to-creatinine ratio 1, 3
• Uric acid 1

Targeted Testing Based on Clinical Suspicion

For suspected primary aldosteronism (most common secondary cause in resistant hypertension):

• Plasma aldosterone-to-renin ratio (ARR) - high ratio (>20) with elevated aldosterone and low renin suggests primary aldosteronism 3, 4
• Note: Mineralocorticoid receptor antagonists raise aldosterone; beta-blockers and direct renin inhibitors lower renin 3

For suspected obstructive sleep apnea:

• Home sleep apnea testing or polysomnography 1, 3, 4

For suspected renovascular disease:

• Renal ultrasound with Doppler duplex 1, 3, 4
• CT or MR renal angiography for confirmation 1, 3

For suspected pheochromocytoma:

• 24-hour urinary metanephrine and normetanephrine 1, 3, 4

For suspected Cushing syndrome:

• 24-hour urinary free cortisol or overnight dexamethasone suppression test 1, 4

Step 4: Pharmacologic Management

Initial Drug Therapy Selection

• First-line agents: Thiazide diuretics, calcium channel blockers, ACE inhibitors, or ARBs 1
• For patients with chronic kidney disease (eGFR <60 mL/min): Use loop diuretics instead of thiazides 1
• Most patients will require ≥2 medications to achieve BP control 1, 5

For Resistant Hypertension (After Excluding Secondary Causes)

• Maximize diuretic therapy first 1
• Use thiazide-like diuretics (chlorthalidone, indapamide) rather than classic thiazides 3
• Add mineralocorticoid receptor antagonist (spironolactone) as fourth-line agent if serum potassium <4.5 mmol/L and eGFR >45 mL/min/1.73m² 3, 4
• Combine agents with different mechanisms of action 1
• Use loop diuretics in patients with CKD or those receiving potent vasodilators (e.g., minoxidil) 1

Blood Pressure Goals

• General target: <140/90 mmHg initially, with long-term target <130/80 mmHg 6
• For patients with diabetes or CKD: <130/80 mmHg 1
• Lowering BP reduces fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions 5

Step 5: Lifestyle Modifications (Essential for ALL Patients)

• Sodium restriction: <1500 mg/day, or minimally reduce by ≥1000 mg/day 1
• Increase dietary potassium: 3500-5000 mg/day 1
• Weight loss if overweight/obese: Target ideal body weight or minimum 1 kg reduction 1
• Physical activity: Aerobic or dynamic resistance exercise 90-150 min/week, or isometric resistance 3 sessions/week 1
• Alcohol moderation: ≤2 drinks/day in men, ≤1 drink/day in women (those consuming ≥3 drinks/day benefit most from reduction, with average BP reduction of 5.5/4.0 mmHg when reducing intake by 50%) 1
• DASH diet 1
• Smoking cessation 1

Step 6: Treatment of Specific Secondary Causes

Primary aldosteronism:

• Unilateral laparoscopic adrenalectomy for unilateral disease 3, 4
• Spironolactone 50-100 mg daily for bilateral disease 3, 4

Obstructive sleep apnea:

• CPAP therapy (modestly lowers BP and CVD risk if actually used by patient) 1, 4
• Weight loss 1

Atherosclerotic renovascular disease:

• Medical therapy is recommended for most patients 1, 4
• Consider revascularization only for: refractory hypertension (uncontrolled on ≥5 drugs including diuretic), worsening renal function (ischemic nephropathy), or intractable heart failure 1

Fibromuscular dysplasia:

• Angioplasty without stenting 1, 4

Step 7: Follow-up and Monitoring

• Recheck BP within 2-4 weeks after medication adjustment 6
• Monitor serum sodium, potassium, and creatinine during diuretic or RAS blocker titration 1
• Recheck creatinine and electrolytes 1-2 weeks after starting ACE inhibitor/ARB 6
• Monitor urinary albumin as marker of CKD progression 1
• Refer to hypertension specialist if BP remains uncontrolled after 6 months of treatment or if secondary cause identified 1, 6

Critical Pitfalls to Avoid

• Do not perform expensive imaging studies before completing basic laboratory screening 3
• Do not combine two RAS blockers (ACE inhibitor + ARB) 3
• Do not overlook medication-induced hypertension - review all prescribed, over-the-counter, and herbal medications before extensive workup 1, 3
• Do not miss white coat hypertension - confirm with home or ambulatory BP monitoring 1
• Do not assume adherence - directly assess in non-judgmental manner 1
• Recognize that even after treating secondary causes, some patients require ongoing antihypertensive therapy due to vascular remodeling 3
• For older patients, assess multiple chronic conditions, frailty, and prognosis - time to benefit may not be realized for some individuals 1