Conditions that contribute to resistant hypertension
| Condition | Diagnostic tests | Comments |
|---|---|---|
| Assess in all patients | ||
| Obstructive sleep apnea | Polysomnography is required for a definitive diagnosis. | Refer patient for testing if their history is suggestive. Activation of the sympathetic nervous system and high aldosterone levels are key drivers of increases in blood pressure. Nocturnal rostral fluid shift (to the head and neck) can increase the severity of sleep apnea.12 |
| Medications | See Box 2 | If feasible, stop all drugs contributing to the elevated blood pressure. |
| Primary aldosteronism (Conn syndrome) | Measurement of plasma aldosterone levels and plasma aldosterone:renin activity ratio before 10 am with the patient in the seated position, because values vary according to posture and time of day.14 The result is positive when the aldosterone:renin ratio is > 750 pmol/L per ng/(mL·h) (or > 144 pmol/L per ng/L if renin mass or concentration is measured [see Dasgupta et al.11]) | Referral to a specialist may be required. Confirmatory suppression tests include salt-loading (intravenous or oral) and fludrocortisone or captopril suppression. If the result is positive, adrenal imaging and bilateral adrenal venous sampling are performed. Adrenalectomy is used to treat unilateral disease. Bilateral disease is treated with a mineralocorticoid receptor antagonist or an epithelial sodium-channel blocker. |
| Renal parenchymal disease (glomerulonephritis and other intrinsic renal disease) | Urinalysis and measurement of serum creatinine level are initial screening tests. If hematuria is present, order ultrasound and urine cytology to check for dysmorphic red blood cells and casts. | Referral to nephrology is recommended. A biopsy may be needed. |
| Assess in selected patients depending on clinical presentation | ||
| Renovascular disease | Computed tomography (CT), magnetic resonance (MR) angiography or arterial Doppler ultrasonography to detect anatomic stenosis. Doppler ultrasonography does not cause contrast nephropathy, but its availability depends on local expertise. Conventional angiography is the gold standard. Renal scanning with captopril can be performed to screen for functional stenosis. | Fibromuscular dysplasia is typically found in young to middle-aged women, and about one-third of the cases are treated successfully with angioplasty.15 The diagnosis should be considered if no other apparent cause of resistant hypertension is present, if a renal bruit is present or if the renin level is high. Atherosclerotic stenosis of the renal artery does not respond well to stenting, and screening is not performed routinely.16 |
| Cushing syndrome | If the syndrome is clinically suspected, measurement of 24-h urine cortisol level or late-night saliva cortisol level, or low-dose dexamethasone suppression test. A positive result in two of three tests is required for diagnosis. | If screening results are positive, adrenocorticotropic hormone testing and imaging of the relevant site (pituitary gland or adrenal gland) are required. |
| Thyroid disease | Measurement of thyroid stimulating hormone. If a central cause is suspected, the thyroxine (T4) level should be measured. | Hypothyroidism is associated with elevated diastolic blood pressure, and hyperthyroidism is associated with elevated systolic pressure. |
| Hypercalcemia | Measurement of ionized or albumin-corrected calcium level in serum. | Vasoconstriction and renal dysfunction are the main mechanisms leading to hypertension. Assessment for the underlying cause, including primary hyperparathyroidism, is warranted. |
| Pheochromocytoma | Headache, diaphoresis and tachycardia (palpitations) constitute the classic triad of symptoms. Measurement of 24-h metanephrine levels is the initial screening test. Some experts recommend measurement of fractionated plasma metanephrine levels if pretest probability for pheochromocytoma is high (e.g., high-risk familial syndrome).17 | Rarely occurs. Scintigraphy with 131iodine m-iodobenzylguanidine is used for localization. An α-blocker with or without a β-blocker is the treatment regimen of choice. Surgical referral is indicated for resectable cases. |
| Coarctation of aorta | In young patients, checking for delayed femoral pulses relative to brachial pulses, and reduced blood pressure in the legs relative to pressure in the arms. | CT or MR angiography should be performed if screening result is positive. |