What are the causes of secondary hypertension (high blood pressure) in patients, particularly those with a history of kidney disease, sleep apnea, or cardiovascular disease?

Secondary Hypertension: Causes and Clinical Recognition

Common Secondary Causes

Obstructive sleep apnea is the most prevalent secondary cause of hypertension, affecting 64% of patients with resistant hypertension, followed by primary aldosteronism (8-20%), renal parenchymal disease, renovascular disease, and drug-induced hypertension. 1, 2

Obstructive Sleep Apnea (25-64% of resistant hypertension cases)

• Presents with snoring, fitful sleep, breathing pauses during sleep, daytime sleepiness, obesity, and loss of normal nocturnal blood pressure fall 2, 1
• Age >50 years, neck circumference ≥41 cm for women and ≥43 cm for men, and presence of snoring are strong predictors 1
• CPAP therapy modestly lowers blood pressure and cardiovascular risk when actually utilized by patients 3

Primary Aldosteronism (8-20% of resistant hypertension)

• Suspect in patients with resistant hypertension, spontaneous or diuretic-induced hypokalemia (though hypokalemia is often absent), muscle cramps or weakness, incidentally discovered adrenal mass, or family history of early-onset hypertension 3, 2
• Screen with plasma aldosterone-to-renin ratio in all adults with confirmed hypertension 4
• Unilateral adrenalectomy is curative for unilateral disease; bilateral disease requires mineralocorticoid receptor antagonists like spironolactone 50-100 mg daily 3, 4

Renal Parenchymal Disease (1-2% prevalence)

• Look for history of urinary tract infections, obstruction, hematuria, urinary frequency, nocturia, analgesic abuse, or family history of polycystic kidney disease 2
• Assess with serum creatinine, eGFR, urinalysis, and urinary albumin-to-creatinine ratio 4

Renovascular Disease (5-34% depending on clinical context)

• Suspect with abrupt onset or worsening hypertension, flash pulmonary edema, early-onset hypertension especially in women, or increase in serum creatinine ≥50% within one week of starting ACE inhibitor or ARB therapy 2, 5
• Fibromuscular dysplasia (typically women in their early 50s) responds to angioplasty without stenting 3
• Atherosclerotic renal artery stenosis should be managed medically in most patients; consider revascularization only for refractory hypertension (≥5 drugs including diuretic), worsening renal function, or intractable heart failure 3

Drug-Induced Hypertension

• Review all medications before pursuing expensive workup 2
• Common culprits include NSAIDs, oral contraceptives, decongestants, stimulants (amphetamines), immunosuppressive agents, steroids, and herbal supplements 3, 2
• Heavy alcohol intake (≥30 drinks per week) significantly increases risk of treatment-resistant hypertension 3

Uncommon but Important Secondary Causes

Pheochromocytoma/Paraganglioma

• Presents with episodic symptoms (headache, palpitations, sweating), labile hypertension, and pallor 2
• Screen with 24-hour urinary catecholamines or metanephrines 2

Cushing Syndrome

• Look for weight gain, moon facies, buffalo hump, purple striae, proximal muscle weakness 2
• Screen with 24-hour urinary free cortisol or overnight dexamethasone suppression test 2

Thyroid Disorders

• Can cause isolated systolic hypertension (hyperthyroidism) or diastolic hypertension (hypothyroidism) 2
• Screen with thyroid-stimulating hormone 2

Aortic Coarctation

• Suspect in young patients with hypertension, diminished femoral pulses, and radio-femoral delay 4, 6
• Confirm with echocardiogram or CT/MR angiography 2

Primary Hyperparathyroidism

• Presents with hypercalcemia 2
• Screen with serum calcium and confirm with parathyroid hormone 2

Clinical Red Flags Requiring Secondary Hypertension Workup

Screen for secondary causes when any of the following are present: 3, 2, 4

• Age-related: Onset <30 years (especially before puberty) or new onset after age 50 years 3, 7
• Severity: Resistant hypertension (BP >140/90 mmHg on ≥3 drugs including diuretic), severe hypertension (≥180/110 mmHg), or accelerated/malignant hypertension 3, 2
• Pattern changes: Abrupt onset, sudden deterioration of previously controlled hypertension, or hypertensive urgency/emergency 3, 2
• Laboratory clues: Unprovoked or excessive hypokalemia 3
• Physical findings: Snoring with daytime sleepiness, abdominal bruits, diminished femoral pulses, or specific endocrine features 3, 7
• Target organ damage: Disproportionate to duration or severity of hypertension 4

Diagnostic Approach

Initial Screening (All Suspected Cases)

• Thorough medication review including over-the-counter drugs and supplements 3, 2
• Basic metabolic panel (sodium, potassium, creatinine, eGFR) 2, 4
• Fasting glucose or HbA1c 3, 4
• Urinalysis and urinary albumin-to-creatinine ratio 4
• Thyroid-stimulating hormone 4
• 12-lead ECG 4

Targeted Testing Based on Clinical Suspicion

• Primary aldosteronism: Plasma aldosterone-to-renin ratio (now recommended for all adults with confirmed hypertension per ESC 2024 guidelines) 4
• Renovascular disease: Renal ultrasound with Doppler, followed by CT or MR angiography 2
• Obstructive sleep apnea: Polysomnography or home sleep apnea testing 2
• Pheochromocytoma: 24-hour urinary catecholamines or metanephrines 2

Critical Pitfalls to Avoid

• Do not pursue expensive imaging before completing basic laboratory screening and medication review 2, 4
• Do not assume primary hypertension in young patients (<30 years) without screening for secondary causes, as renal parenchymal disease and coarctation are common in this age group 6, 5
• Do not overlook drug-induced hypertension—NSAIDs and other common medications are frequently missed culprits 3, 2
• Recognize that hypokalemia is often absent in primary aldosteronism—normal potassium does not exclude the diagnosis 3
• Consider that delayed diagnosis leads to vascular remodeling, potentially resulting in residual hypertension even after treating the underlying cause 4