What is the recommended evaluation and work‑up for a young adult under 40 years old with newly diagnosed hypertension?

Young Hypertension Work-Up

All young adults under 40 with newly diagnosed hypertension require a comprehensive evaluation that includes basic laboratory screening, assessment for target organ damage, and a high index of suspicion for secondary causes—which affect up to 10% of this population and are potentially reversible. 1, 2, 3

Initial Diagnostic Confirmation

• Confirm the diagnosis using accurate office blood pressure measurements on at least three separate visits, supplemented with home or ambulatory blood pressure monitoring to exclude white coat hypertension. 4
• For patients under 30 years, a thigh blood pressure measurement is indicated if brachial BP is elevated; if the thigh measurement is lower than arm pressures, consider coarctation of the aorta. 1
• Automated oscillometric devices provide repeated measurements without a provider present, minimizing white coat effect. 1

History: Red Flags for Secondary Hypertension

Look specifically for these clinical clues that suggest a secondary cause:

• Age of onset <30 years, especially without family history of hypertension 1, 2, 3
• Severe hypertension (BP ≥180/110 mmHg) or hypertensive emergency 1, 2
• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive drugs including a diuretic) 5, 2
• Abrupt onset or sudden worsening of previously controlled hypertension 5, 2, 3
• Episodic symptoms: palpitations, sweating, headaches (pheochromocytoma) 1, 5
• Snoring, hypersomnolence, witnessed apneas (obstructive sleep apnea) 1, 5
• Muscle cramps, weakness (hypokalemia from primary aldosteronism) 1, 5
• Weight gain, central obesity, easy bruising, purple striae (Cushing's syndrome) 1, 5
• Medication use: NSAIDs, cocaine, amphetamines, oral contraceptives 1

Physical Examination: Specific Findings to Assess

• Radio-femoral pulse delay or BP differential between arms and legs (coarctation of the aorta) 1, 5
• Abdominal bruits (renovascular disease) 5
• Central obesity, moon facies, buffalo hump, wide purple striae >1 cm (Cushing's syndrome) 5
• Enlarged kidneys on palpation (polycystic kidney disease) 5
• Neck circumference >40 cm (obstructive sleep apnea) 5
• Orthostatic hypotension (decline >20 mmHg systolic or >10 mmHg diastolic after 1 minute standing) 1

Basic Laboratory Tests (Required for All Patients)

These tests screen for secondary causes, assess cardiovascular risk, and establish baseline for treatment: 1

• Serum creatinine with estimated GFR (renal parenchymal disease) 1, 6, 4
• Serum sodium and potassium (hypokalemia suggests primary aldosteronism, though most cases are normokalemic) 1, 6, 5
• Urinalysis with albumin-to-creatinine ratio (renal damage, proteinuria) 1, 6, 4
• Fasting blood glucose or HbA1c (diabetes, cardiovascular risk) 1, 6
• Lipid profile (cardiovascular risk stratification) 1, 6
• Thyroid-stimulating hormone (hypothyroidism and hyperthyroidism are remediable causes) 1, 6
• 12-lead electrocardiogram (left ventricular hypertrophy, target organ damage) 1, 6, 4

Screening for Primary Aldosteronism

This is critical because primary aldosteronism affects 8-20% of resistant hypertension cases and is the most common treatable secondary cause: 5, 2

• Plasma aldosterone-to-renin ratio (ARR) should be measured in all young adults with confirmed hypertension, particularly those with resistant hypertension, spontaneous or diuretic-induced hypokalemia, or family history of early-onset hypertension. 6, 5
• The 2024 European Society of Cardiology guidelines now recommend ARR screening in all adults with confirmed hypertension (Class IIa recommendation). 6, 5
• Important caveat: ACE inhibitors and ARBs can cause false-negative results by lowering aldosterone and raising renin; beta-blockers and mineralocorticoid receptor antagonists also affect the ratio. 5

Assessment of Target Organ Damage

Young adults with hypertension require evaluation for target organ damage, which influences treatment urgency and intensity: 1, 4

• Echocardiography is indicated if considering pharmacologic treatment, if ECG shows left ventricular hypertrophy, or in patients with severe/uncontrolled hypertension. 1, 6
• Left ventricular hypertrophy independently predicts future cardiovascular events and is more useful for risk assessment in younger patients. 1
• Urinary albumin-to-creatinine ratio should be assessed at diagnosis and annually to monitor for kidney damage. 4

Additional Testing Based on Clinical Suspicion

If red flags are present, proceed with targeted investigations:

For Renovascular Disease (if abrupt onset, flash pulmonary edema, or creatinine rise >50% with ACE inhibitor/ARB):

• Renal ultrasound with Doppler as first-line imaging 6, 5
• CT or MR renal angiography for confirmation 6, 5

For Pheochromocytoma (if episodic symptoms, labile BP):

• 24-hour urinary fractionated metanephrines or plasma free metanephrines 1, 6, 5
• Abdominal/adrenal imaging after biochemical confirmation 5

For Cushing Syndrome (if clinical features present):

• Late-night salivary cortisol or 24-hour urinary free cortisol 6, 5

For Obstructive Sleep Apnea (if snoring, daytime sleepiness, obesity):

• Overnight polysomnography (apnea-hypopnea index >5 confirms diagnosis) 5

Treatment Initiation Strategy

The approach differs based on BP stage and cardiovascular risk:

• Stage 1 hypertension (130-139/80-89 mmHg) with 10-year ASCVD risk <10%: Initiate lifestyle modifications and reassess in 3-6 months. 1
• Stage 1 hypertension with 10-year ASCVD risk ≥10%: Initiate both lifestyle modifications and pharmacologic therapy; reassess in 1 month. 1
• Stage 2 hypertension (≥140/90 mmHg): Initiate combination therapy with two agents of different classes plus lifestyle modifications; evaluate or refer within 1 month. 1, 2
• Very high BP (≥180/110 mmHg): Prompt evaluation and treatment within 1 week. 1

Lifestyle Modifications (All Patients)

• Sodium restriction to <2400 mg/day 5, 7
• Weight loss if overweight or obese 7
• DASH dietary pattern with high potassium intake 4, 7
• Regular aerobic physical activity 4, 7
• Alcohol limitation or elimination 4, 7

Blood Pressure Targets

• Target BP <130/80 mmHg for most young adults under 65 years 4, 7
• For adolescents ≥13 years, target <130/80 mmHg or <90th percentile for age, sex, and height 4

Common Pitfalls to Avoid

• Failing to screen for secondary causes in young adults is a critical error, as approximately 10% have an identifiable, potentially reversible cause. 2, 3
• Relying solely on office BP measurements without home or ambulatory monitoring can lead to misdiagnosis of white coat hypertension. 4
• Delaying echocardiography in patients with severe or resistant hypertension misses important target organ damage. 1, 4
• Not measuring ARR in resistant hypertension misses the most common treatable secondary cause. 6, 5
• Underestimating lifetime cardiovascular risk in young adults with hypertension—even stage 1 hypertension carries a hazard ratio of 1.75 for cardiovascular events. 4

Referral Indications

• Positive screening tests requiring confirmatory testing (e.g., elevated ARR, elevated metanephrines) 5
• Stage 2 hypertension in patients <25 years may warrant referral to a cardiologist or hypertension specialist 1
• Complex cases needing specialized procedures such as adrenal vein sampling 5
• Consideration for surgical intervention (e.g., unilateral adrenalectomy for primary aldosteronism) 5