What laboratory tests and treatment are recommended for a patient with uncontrolled hypertension?

Laboratory Work for Uncontrolled Hypertension

All patients with uncontrolled hypertension require basic laboratory testing including sodium, potassium, serum creatinine with eGFR, fasting glucose, lipid profile, urinalysis with albumin-to-creatinine ratio, and a 12-lead ECG. 1, 2

Essential Initial Laboratory Tests

Blood Tests (Required for All Patients)

• Serum sodium and potassium to detect electrolyte abnormalities that may suggest secondary causes like primary aldosteronism or guide diuretic therapy 1
• Serum creatinine with estimated glomerular filtration rate (eGFR) to assess kidney function and detect chronic kidney disease 1, 2
• Fasting blood glucose to identify diabetes mellitus, which significantly increases cardiovascular risk and lowers treatment thresholds 1, 2
• Lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) for cardiovascular risk stratification 1
• Thyroid-stimulating hormone to detect hypothyroidism and hyperthyroidism, both remediable causes of hypertension 1, 2, 3
• Complete blood count (hemoglobin/hematocrit) to detect anemia or other hematologic abnormalities 1, 3

Urine Tests (Required for All Patients)

• Urinalysis with dipstick for microscopic examination and protein detection 1
• Urinary albumin-to-creatinine ratio rather than dipstick alone, as it is more sensitive for detecting early kidney damage and serves as an independent cardiovascular risk marker 1, 2, 3

Cardiac Testing (Required for All Patients)

• 12-lead electrocardiogram to detect atrial fibrillation, left ventricular hypertrophy, and ischemic heart disease 1, 2

Additional Testing Based on Clinical Suspicion

When to Screen for Secondary Hypertension

Screen for secondary causes when any of these features are present 1, 2, 4:

• Age of onset <30 years (or <40 years per ESC 2024 guidelines)
• Severe or resistant hypertension (BP >140/90 mmHg despite ≥3 antihypertensive medications including a diuretic)
• Abrupt onset or sudden deterioration of previously controlled hypertension
• Absence of family history of hypertension
• Target organ damage disproportionate to duration or severity of hypertension

Targeted Testing for Specific Secondary Causes

For primary aldosteronism (8-20% of resistant hypertension cases) 1, 4:

• Plasma aldosterone-to-renin ratio as initial screening test (the ESC 2024 guidelines now recommend this for all adults with confirmed hypertension, Class IIa) 2, 4
• Clinical clues: spontaneous or diuretic-induced hypokalemia, muscle cramps/weakness, resistant hypertension 1

For renovascular disease (5-34% in selected populations) 1, 4:

• Renal Duplex Doppler ultrasound as initial test, followed by CT or MR angiography for confirmation 1, 4
• Clinical clues: abrupt onset or worsening hypertension, flash pulmonary edema, early-onset hypertension especially in women (fibromuscular dysplasia), abdominal systolic-diastolic bruit 1, 4

For pheochromocytoma 1, 4:

• Plasma free metanephrines or 24-hour urinary metanephrines when specifically suspected
• Clinical clues: episodic symptoms (sweating, palpitations, headaches), labile hypertension 1, 4

For Cushing syndrome 1, 4:

• Late-night salivary cortisol or other screening tests for cortisol excess 1
• Clinical clues: central obesity, facial rounding, easy bruisability, fatty deposits and colored striae 1

For obstructive sleep apnea (25-50% of resistant hypertension) 4:

• Home sleep apnea testing or polysomnography 4
• Clinical clues: snoring, daytime sleepiness, neck circumference >40 cm, obesity, non-dipping nocturnal BP pattern 1, 4

Optional Advanced Testing

Echocardiography is reasonable when 1, 2:

• ECG shows abnormalities
• Cardiac murmurs are present
• Patient has cardiac symptoms or signs of left ventricular dysfunction
• Detection of left ventricular hypertrophy would influence treatment decisions

Additional imaging may be considered 1, 2:

• Renal ultrasound for suspected kidney disease, chronic kidney disease assessment, or resistant hypertension
• Carotid ultrasound to detect atherosclerotic plaques or stenosis in patients with documented vascular disease elsewhere
• Fundoscopy in severe/uncontrolled hypertension (BP >180/110 mmHg) to assess for retinal changes, hemorrhages, or papilledema

Additional laboratory tests 1:

• Serum uric acid levels (elevated in 25% of hypertensive patients and should be treated)
• Liver function tests when clinically indicated

Treatment Approach Based on Laboratory Findings

Optimize Antihypertensive Regimen

• First-line therapy consists of thiazide or thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide), ACE inhibitors or angiotensin receptor blockers, and calcium channel blockers 5
• For resistant hypertension, ensure optimal doses of complementary medications including an appropriate diuretic 6, 5
• Add spironolactone as fourth-line agent if serum potassium <4.5 mmol/L and eGFR >45 ml/min/1.73m² 4

Address Modifiable Factors

• Lifestyle modifications including weight loss, dietary sodium restriction (<2 g/day), potassium supplementation, physical activity, and limited alcohol consumption 5
• Review medications that may interfere with BP control (NSAIDs, cocaine, amphetamines, alcohol) 1, 7

Monitor for Complications

• Hypokalemia or hyperkalemia may occur with diuretic therapy or ACE inhibitors/ARBs; monitor serum potassium during titration 1, 8
• Worsening renal function (increases in BUN and creatinine) may occur, especially with bilateral renal artery stenosis; monitor closely in first few weeks 1, 8
• Small decreases in hemoglobin and hematocrit occur frequently but are rarely clinically significant unless another cause of anemia coexists 8

Common Pitfalls to Avoid

• Do not skip the urinary albumin-to-creatinine ratio in favor of dipstick alone; it is more sensitive for detecting early kidney damage 2, 3
• Do not overlook secondary causes in young patients (<30 years), those with resistant hypertension, or those with abrupt onset; the prevalence is higher than in gradual-onset hypertension 2, 4, 3
• Do not perform expensive imaging studies before completing basic laboratory screening 4
• Do not fail to consider medication-induced hypertension before extensive workup 4
• Monitor serum electrolytes regularly during diuretic or RAS blocker therapy to detect hyperkalemia (risk factors: renal insufficiency, diabetes, concomitant potassium-sparing diuretics or supplements) 8
• Confirm hypertension with repeated measurements before extensive workup, but do not delay basic laboratory testing once hypertension is confirmed 3