What baseline laboratory tests should be ordered for an adult with uncontrolled hypertension despite lifestyle measures and at least one antihypertensive medication?

Laboratory Evaluation for Uncontrolled Hypertension

For an adult with uncontrolled hypertension despite lifestyle measures and at least one antihypertensive medication, order a comprehensive metabolic panel (including fasting glucose, creatinine with eGFR, sodium, potassium, and calcium), complete blood count, lipid profile, thyroid-stimulating hormone, urinalysis with urine albumin-to-creatinine ratio, and a 12-lead electrocardiogram. 1

Core Baseline Laboratory Tests

The 2017 ACC/AHA guideline specifies the following basic testing panel for all patients with hypertension to assess cardiovascular risk, detect target-organ damage, and screen for secondary causes: 1

• Fasting blood glucose (or comprehensive metabolic panel that includes glucose) 1
• Complete blood count 1
• Lipid profile (total cholesterol, LDL, HDL, triglycerides) 1
• Serum creatinine with estimated glomerular filtration rate (eGFR) to assess kidney function 1
• Serum electrolytes: sodium, potassium, and calcium 1
• Thyroid-stimulating hormone (TSH) to detect hypothyroidism and hyperthyroidism, both remediable causes of hypertension 1
• Urinalysis 1
• 12-lead electrocardiogram to assess for left ventricular hypertrophy and other cardiac abnormalities 1

Optional but Strongly Recommended Tests

• Urine albumin-to-creatinine ratio provides critical information on target-organ damage and chronic kidney disease progression, particularly important when titrating RAS blockers or diuretics 1, 2
• Hemoglobin A1c if fasting glucose is not obtained or if diabetes screening is indicated 1

Monitoring During Treatment Optimization

When uncontrolled hypertension persists despite treatment, serial monitoring of serum sodium and potassium is essential during diuretic or RAS blocker titration, and serum creatinine with urinary albumin should be tracked as markers of CKD progression. 1

When to Screen for Secondary Hypertension

Consider additional laboratory testing for secondary causes when any of the following are present: 1, 2

• Resistant hypertension (BP ≥130/80 mm Hg on ≥3 optimally dosed agents including a diuretic, or requiring ≥4 agents) 2
• Abrupt onset or worsening of previously controlled hypertension 2
• Onset before age 30 years 2
• Accelerated or malignant hypertension 2
• Disproportionate target-organ damage for the level of BP 1
• Unexplained or severe hypokalemia (suggesting primary aldosteronism) 1

Secondary causes account for approximately 5–34% of resistant hypertension cases (renovascular disease), 8–20% (primary aldosteronism), and 1–2% (renal parenchymal disease). 2

Critical Pitfalls to Avoid

• Failing to obtain TSH: This simple test identifies two easily remediable causes of hypertension that are frequently overlooked 1
• Omitting urine albumin-to-creatinine ratio: This marker of target-organ damage guides treatment intensity and predicts cardiovascular risk 1, 2
• Not monitoring electrolytes during medication titration: Hypokalemia from diuretics or hyperkalemia from combined RAS blocker and mineralocorticoid receptor antagonist therapy can be dangerous 1, 3
• Inadequate BP measurement technique: Before ordering extensive laboratory workup, confirm true uncontrolled hypertension with home or ambulatory monitoring to exclude white-coat effect, which accounts for 20–30% of apparent uncontrolled cases 2, 4
• Ignoring medication adherence: Non-adherence is the leading cause of apparent resistant hypertension; approximately 25% of patients never fill the initial prescription 2
• Overlooking interfering substances: NSAIDs, decongestants, stimulants, oral contraceptives, and other agents can elevate BP and should be reviewed before intensifying therapy 1, 2