A 65-year-old man comes to the office for follow-up for inadequately controlled hypertension. The patient has no symptoms except pain in the right thigh when walking uphill or climbing stairs; the pain resolves promptly with rest. Medical history includes coronary artery disease with stable angina that required coronary angioplasty and stenting 2 years ago; the patient also has hypercholesterolemia, a 20-year history of hypertension, and a 10-year history of type 2 diabetes mellitus. Medications include aspirin, metoprolol, valsartan, hydrochlorothiazide, amlodipine, atorvastatin, and metformin. The patient smokes 1½ packs of cigarettes daily and does not consume alcohol. Blood pressure is 177/100 mm Hg in the left arm and 180/100 mm Hg in the right. Which of the following is the most likely additional finding in this patient?
Secondary causes of hypertension | |
Condition | Clinical clues/features |
Renal parenchymal disease |
|
Renovascular disease |
|
Primary hyperaldosteronism |
|
Obstructive sleep apnea |
|
Pheochromocytoma |
|
Cushing syndrome |
|
Thyroid disease |
|
Primary hyperparathyroidism |
|
Coarctation of the aorta |
|
This patient has resistant hypertension, defined as persistent blood pressure (BP) elevation despite an appropriate regimen of ≥3 antihypertensive agents of different classes, 1 of which is a diuretic. Patients with resistant hypertension should be evaluated for secondary causes.
Renovascular hypertension (eg, renal artery stenosis [RAS]) is a very common and correctable cause of resistant hypertension. Clinical features suggesting renovascular hypertension include the following:
This patient with resistant hypertension has clinical evidence of diffuse atherosclerosis given his coronary artery disease (angina, stent) and intermittent claudication symptoms (eg, leg pain with activity, relieved by rest) concerning for peripheral artery disease (PAD). RAS is very common in such patients (eg, 45% of patients with PAD). If present, a continuous (ie, systolic-diastolic) abdominal bruit, typically best heard in the epigastric, periumbilical, or flank area and lateralizing to one side, is highly suggestive of renovascular disease (99% specificity).
(Choice B) A high plasma aldosterone/renin ratio >20:1 is seen in patients with primary hyperaldosteronism. Drugs such as ACE inhibitors or angiotensin receptor blockers (eg, valsartan) can elevate plasma renin concentration (PRC) and have variable effects on plasma aldosterone levels, but even in patients taking these drugs, a low PRC is suggestive of primary hyperaldosteronism. Although primary hyperaldosteronism is a common cause of resistant hypertension, the presence of diffuse atherosclerosis makes RAS the more likely cause of this patient's hypertension.
(Choice C) Increased 24-hour urinary free cortisol excretion is observed in Cushing syndrome. Although this syndrome can cause hypertension, patients typically have central obesity, facial plethora, muscle weakness and wasting, thin skin, and neuropsychologic changes.
(Choice D) Urinary excretion of vanillylmandelic acid is increased in pheochromocytoma, which often presents with paroxysmal hypertension even though persistent hypertension may occur. Associated symptoms include episodic pounding headaches, palpitations, and diaphoresis.
(Choice E) This patient has nonsignificant interarm BP discrepancy; significant (eg, >10 mm Hg) interarm discrepancy, not seen here, would suggest subclavian stenosis. Rib notching on chest x-ray (enlarged collateral intercostal vessels) is seen with coarctation of the aorta (CoA), which causes higher BPs in the arms than in the lower extremities. Compared to RAS, CoA is a much less common cause of resistant hypertension and usually presents in children; in adults with CoA, severe hypertension can cause headache, epistaxis, or heart failure.
Educational objective:
Renovascular hypertension should be suspected in patients with resistant hypertension and diffuse atherosclerosis, asymmetric kidney size, recurrent flash pulmonary edema, or elevation in serum creatinine >30% from baseline after starting an ACE inhibitor or angiotensin receptor blocker. A continuous abdominal bruit has a high specificity for renovascular hypertension.