What is the recommended workup for confirmed hypertension?

Workup for Confirmed Hypertension

All patients with confirmed hypertension require a standardized baseline laboratory evaluation including serum electrolytes (sodium, potassium), serum creatinine with eGFR, urinalysis with albumin-to-creatinine ratio, fasting glucose or HbA1c, lipid profile, thyroid-stimulating hormone, and a 12-lead ECG. 1, 2, 3

Essential Baseline Laboratory Tests

The following tests must be obtained in every patient with newly diagnosed hypertension:

• Serum sodium and potassium – spontaneous or diuretic-induced hypokalemia strongly suggests primary aldosteronism, which accounts for 8-20% of resistant hypertension 1, 4
• Serum creatinine and estimated glomerular filtration rate (eGFR) – identifies chronic kidney disease and establishes baseline renal function 1, 2, 3
• Urinalysis with albumin-to-creatinine ratio – detects early renal damage and stratifies cardiovascular risk; dipstick alone is insufficient 1, 2
• Fasting glucose or HbA1c – uncovers diabetes mellitus, present in 15-20% of hypertensive patients 1, 3
• Fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides) – 30% of hypertensive patients have lipid disorders 1
• Thyroid-stimulating hormone (TSH) – screens for thyroid dysfunction as a reversible cause 1, 2
• 12-lead electrocardiogram – detects left ventricular hypertrophy, atrial fibrillation, and ischemic heart disease 1, 2

A recent pilot study demonstrated that complete baseline laboratory testing resulted in significantly better systolic blood pressure control at 12 months (129.9 mmHg vs 142.8 mmHg, P=0.003) compared to partial workup, and identified important comorbidities including diabetes (8.4%), chronic kidney disease (7.5%), and dyslipidemia (54.2%). 3

Cardiovascular Risk Assessment

More than 50% of hypertensive patients have additional cardiovascular risk factors that proportionally increase the risk of coronary, cerebrovascular, and renal disease. 1 The evaluation should include:

• Age >65 years, male sex, heart rate >80 beats/min, increased body weight 1
• Family history of premature cardiovascular disease 1
• Smoking status, alcohol intake, sedentary lifestyle 1

History and Physical Examination

Symptoms Requiring Assessment

• Hypertension-related symptoms: chest pain, shortness of breath, palpitations, claudication, peripheral edema, headaches, blurred vision, nocturia, hematuria, dizziness 1
• Medication history: current antihypertensive regimen, adherence, recent changes, use of BP-elevating substances (NSAIDs, decongestants, oral contraceptives, cyclosporine) 5, 6

Physical Examination Findings

The examination should specifically assess for:

• Pulse rate, rhythm, character; jugular venous pressure; apex beat; extra heart sounds; basal crackles; peripheral edema 1
• Blood pressure in both arms simultaneously – use the arm with higher BP for subsequent measurements 1
• Carotid, abdominal, and femoral bruits – suggest vascular disease 1
• Radio-femoral delay – indicates coarctation of the aorta 1, 2
• BMI/waist circumference, neck circumference >40 cm (obstructive sleep apnea) 1, 4

Screening for Secondary Hypertension

When to Screen

The 2024 ESC guidelines (Class IIa) recommend measuring plasma aldosterone-to-renin ratio (ARR) in all adults with confirmed hypertension, representing a paradigm shift from selective screening. 2, 4 Additional screening is mandatory when:

• Age of onset <30 years (or <40 years per ESC 2024) without family history 4, 6
• Resistant hypertension (BP ≥140/90 mmHg despite optimal doses of ≥3 drugs including a diuretic) 1, 4, 6
• Sudden onset or rapid worsening of previously controlled hypertension 1, 4, 6
• Severe hypertension (≥180/110 mmHg) or hypertensive emergency 4
• Target organ damage disproportionate to duration or severity 4, 6

Clinical Clues by Etiology

Primary aldosteronism (8-20% of resistant hypertension):

• Muscle weakness, tetany, cramps, arrhythmias from hypokalemia 1, 4
• Family history of early-onset hypertension or stroke <40 years 4

Renovascular disease:

• Flash pulmonary edema 1, 4
• Abdominal systolic-diastolic bruits 4
• ≥50% rise in creatinine within one week after starting ACE inhibitor/ARB 4

Pheochromocytoma:

• Episodic sweating, palpitations, frequent headaches 1, 4
• Labile or paroxysmal hypertension 4

Obstructive sleep apnea (25-50% of resistant hypertension):

• Snoring, witnessed apneas, daytime sleepiness 1, 4
• Obesity with neck circumference >40 cm 1, 4
• Non-dipping nocturnal BP pattern on ambulatory monitoring 4

Cushing syndrome:

• Central obesity with thin extremities, wide (>1 cm) purple striae, easy bruising 4
• Proximal muscle weakness, moon facies, buffalo hump 4

Additional Diagnostic Tests (When Indicated)

Imaging Studies

• Echocardiography: indicated for abnormal ECG, cardiac symptoms, or murmurs; detects left ventricular hypertrophy, systolic/diastolic dysfunction, atrial dilation 1, 2
• Renal Duplex Doppler ultrasound: first-line imaging for suspected renovascular disease 1, 4
• CT or MR renal angiography: confirmatory test for renovascular disease 1, 4
• Fundoscopy: recommended if BP >180/110 mmHg to evaluate for hypertensive emergency and retinal changes 1, 2

Confirmatory Tests for Secondary Causes

Primary aldosteronism:

• Plasma aldosterone-to-renin ratio (ARR) as initial screening 2, 4
• Confirmatory testing with IV saline suppression or oral sodium loading 4
• Adrenal CT for localization; adrenal vein sampling if surgery contemplated 4

Pheochromocytoma:

• 24-hour urinary metanephrines or plasma free metanephrines 1, 4
• Abdominal/adrenal imaging after biochemical confirmation 4

Cushing syndrome:

• Late-night salivary cortisol or 24-hour urinary free cortisol 1, 4

Obstructive sleep apnea:

• Overnight polysomnography (AHI >5 confirms OSA, >30 indicates severe disease) 4

Common Pitfalls to Avoid

• Medication non-adherence accounts for a large share of apparent resistant hypertension; explicitly ask about missed doses, side effects, and cost barriers 6
• White-coat hypertension occurs in 20-30% of apparent resistant cases; confirm with ambulatory or home BP monitoring (home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg confirms true hypertension) 1, 6
• ACE inhibitors and ARBs lower aldosterone and raise renin, potentially causing false-negative ARR results 4
• Expensive imaging studies should not be performed before completing basic laboratory screening 4

Referral Indications

Refer to a hypertension specialist or endocrinologist when:

• Positive screening tests (e.g., elevated ARR, metanephrines) require confirmatory evaluation 4
• Complex procedures such as adrenal vein sampling are needed 4
• Surgical intervention is being considered (e.g., unilateral adrenalectomy for primary aldosteronism) 4
• BP remains uncontrolled after ≥6 months of optimal medical therapy 4