What laboratory tests should be ordered for a patient with hypertension to evaluate secondary causes, organ damage, and cardiovascular risk?

Laboratory Testing for Hypertension Evaluation

All hypertensive patients require a core panel of blood tests (sodium, potassium, creatinine with eGFR), urinalysis with albumin-to-creatinine ratio, fasting glucose or HbA1c, lipid profile, and a 12-lead ECG to assess cardiovascular risk, detect organ damage, and screen for secondary causes. 1

Essential Baseline Laboratory Tests (Required for All Patients)

Blood Chemistry Panel

• Serum sodium and potassium: Hypokalemia (spontaneous or diuretic-induced) strongly suggests primary aldosteronism, which accounts for 8-20% of resistant hypertension 1
• Serum creatinine with estimated glomerular filtration rate (eGFR): Identifies chronic kidney disease and establishes baseline renal function 1, 2
• Fasting blood glucose or HbA1c: Diabetes coexists in 15-20% of hypertensive patients and dramatically increases cardiovascular risk 1, 2
• Fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides): Lipid disorders occur in 30% of hypertensive patients and proportionally increase coronary, cerebrovascular, and renal disease risk 1

Urine Testing

• Urinary albumin-to-creatinine ratio (morning spot urine): More sensitive than dipstick for detecting early kidney damage and stratifying cardiovascular risk 1, 3
• Dipstick urinalysis: Screens for hematuria and proteinuria 1

Additional Baseline Tests

• Thyroid-stimulating hormone (TSH): Screens for hypo- or hyperthyroidism, both remediable causes of hypertension 1, 2
• Complete blood count: Evaluates for anemia or hematologic abnormalities 2
• 12-lead electrocardiogram: Detects left ventricular hypertrophy (present in moderate-severe cases), atrial fibrillation, and ischemic heart disease 1, 3

Screening for Secondary Hypertension

When to Screen Aggressively

Screen immediately if any of these red flags are present:

• Age of onset <30 years (or <40 years per ESC 2024) 4, 5
• Resistant hypertension (BP >140/90 mmHg on ≥3 drugs including a diuretic at optimal doses) 4, 5, 6
• Sudden onset or rapid worsening of previously controlled hypertension 4, 5
• Severe hypertension (systolic >180 mmHg or diastolic >110 mmHg) 4, 5
• Target organ damage disproportionate to duration or severity of hypertension 4, 5

Primary Aldosteronism Screening

• Plasma aldosterone-to-renin ratio (ARR): The ESC 2024 guidelines (Class IIa) now recommend measuring ARR in all adults with confirmed hypertension, representing a paradigm shift from selective screening 4, 5
• This test has high negative predictive value and should be obtained in the morning 4
• Critical pitfall: ACE inhibitors and ARBs can cause false-negative results by lowering aldosterone and raising renin; short-acting dihydropyridine calcium channel blockers can also interfere 4

Additional Secondary Cause Testing (When Clinically Indicated)

For suspected renovascular disease (abrupt onset, flash pulmonary edema, abdominal bruits, ≥50% creatinine rise after starting ACE-I/ARB):

• Renal Doppler ultrasound as initial test 1, 4
• CT or MR renal angiography for confirmation 1, 4

For suspected pheochromocytoma (episodic sweating, palpitations, headaches, labile BP):

• 24-hour urinary metanephrines/normetanephrines or plasma free metanephrines 1, 4

For suspected Cushing syndrome (central obesity, wide purple striae, easy bruising, moon facies, buffalo hump):

• Late-night salivary cortisol or 24-hour urinary free cortisol 1, 4
• Low-dose dexamethasone suppression test 1

For suspected obstructive sleep apnea (25-50% of resistant hypertension; snoring, daytime sleepiness, neck circumference >40 cm, non-dipping BP pattern):

• Overnight polysomnography 1, 4

For suspected hyperparathyroidism:

• Parathyroid hormone (PTH), calcium, and phosphate 1

Optional Advanced Testing

Echocardiography

• Indicated when ECG shows abnormalities, cardiac symptoms are present, or hypertension is uncontrolled 2, 3
• Detects left ventricular hypertrophy, systolic/diastolic dysfunction, and atrial dilation with superior sensitivity compared to ECG 1, 3
• May be performed in all newly diagnosed patients if resources permit, as it predicts cardiovascular events over 5 years 3

Additional Organ Damage Assessment

• Serum uric acid: Elevated in 25% of hypertensive patients; provides additional risk stratification 1
• Liver function tests: Part of comprehensive metabolic assessment 1
• Carotid ultrasound: Detects atherosclerotic plaques and stenosis in patients with known vascular disease 1
• Fundoscopy: Recommended if BP >180/110 mmHg to evaluate for hypertensive emergency and retinal changes 1

Critical Pitfalls to Avoid

• Do not rely solely on office BP measurements: Confirm diagnosis with home or ambulatory BP monitoring to exclude white coat hypertension (present in 20-30% of apparent resistant cases) 4, 2
• Do not use urine dipstick alone: Quantitative albumin-to-creatinine ratio is required to detect early kidney damage 2, 3
• Do not perform expensive imaging before completing basic laboratory screening: Establish biochemical abnormalities first 4
• Do not overlook medication-induced hypertension: NSAIDs, decongestants, oral contraceptives, cyclosporine, and erythropoietin can elevate BP 4
• Do not forget to assess medication adherence: Non-adherence accounts for a large proportion of apparent resistant hypertension 4, 6
• Do not test ARR while patient is on interfering medications: Mineralocorticoid receptor antagonists, beta-blockers, and direct renin inhibitors alter test interpretation 4

Referral Indications

Refer to a hypertension specialist or endocrinologist when:

• Positive screening tests (ARR, metanephrines, cortisol) require confirmatory testing 4, 5
• Complex procedures such as adrenal vein sampling are needed 4, 5
• Surgical intervention (e.g., unilateral adrenalectomy for primary aldosteronism) is being considered 4, 5
• BP remains uncontrolled after ≥6 months of optimal medical therapy 4