A 42-year-old woman presents for post hospitalization follow-up. She was recently admitted to hospital for 3 days due to sudden-onset dyspnea. Her blood pressure on presentation was 164/98 mmHg. Her examination and chest radiograph were consistent with pulmonary edema. She responded well to intravenous diuretics and was discharged on lisinopril. She has no family history of hypertension. On examination during the clinic visit, her blood pressure is 158/90 mmHg. She is normal in weight and has a normal cardiovascular examination except for a right-sided carotid bruit. Her blood tests are notable for a rise in creatinine from 0.9 to 1.8 mg/dL since hospital discharge.
What is the most appropriate follow-up investigation?
Duplex ultrasonography of the renal arteries. This young woman likely has hypertension secondary to fibromuscular dysplasia (FMD). FMD is a noninflammatory, nonatherosclerotic vascular condition typically affecting young women. It most frequently presents with hypertension, transient ischemic attack, stroke, or an asymptomatic cervical bruit. Sudden onset of pulmonary edema and a significant rise in creatinine after ACEI/ARB initiation are also common manifestations and reflect the presence of renal artery stenosis. About 60% to 75% of cases of FMD involve the renal arteries. Duplex ultrasonography is a noninvasive investigation that is highly specific and sensitive for renal artery stenosis, whether the stenosis is caused by atherosclerosis or FMD, and therefore is often the first test for diagnosis of this condition. Duplex ultrasonography of the carotids would also have been a good choice in this patient given the presence of a carotid bruit. The classic “string-of-beads” appearance of the arteries may be seen on angiography. The clinical history is not suggestive of pheochromocytoma (Answer c) or Cushing syndrome (Answer d).
An 83-year-old woman presents to cardiology clinic for follow-up of her hypertension and coronary artery disease. Her only current symptom is dizziness on standing from a sitting position. The dizziness caused her to lose balance and fall on two occasions. Her current resting blood pressure is 144/90 mmHg with pulse 60 beats per minute (bpm). Her medications include hydrochlorothiazide 25 mg daily, doxazosin 2 mg daily, metoprolol XL 50 mg daily, simvastatin 40 mg daily, and aspirin 81 mg daily.
What changes in medication therapy would you recommend?
Discontinue doxazosin and start lisinopril 5 mg daily. The likely culprit of this patient’s postural dizziness and falls is doxazosin. Elderly patients are more susceptible to drug side effects and management of hypertension should take into account such symptoms. Doxazosin demonstrated less effective blood pressure lowering than a thiazide in the antihypertensive and lipid lowering treatment to prevent heart attack trial (ALLHAT) study and was associated with excess cardiovascular events and incident heart failure. It would therefore be appropriate to discontinue doxazosin. There is minimal additional efficacy increasing from 25 to 50 mg of hydrochlorothiazide. The β-blocker should be continued due to the coronary artery disease history, but increasing to 100 mg metoprolol risks bradycardia. Clonidine 0.4 mg twice daily would also lower the heart rate and would be an excessive dose for initiation in an elderly patient who is already near blood pressure goal. The JNC recommendation of a “start low, go slow” approach in the elderly is intended to limit drug side effects, including hypotension. The discontinuation of doxazosin and initiation of 5 mg lisinopril is therefore the most appropriate option.
A 64-year-old woman with hypertension, stage III chronic kidney disease (CKD), and diabetes is not yet at blood pressure goal on the following antihypertensives: lisinopril 40 mg, hydrochlorothiazide 25 mg, and metoprolol XL150 mg.
Which of the following additional agents is contraindicated?
Aliskiren. The U.S. Food and Drug Administration issued a black box warning in 2012 that aliskiren should not be used with ACEIs or ARBs in patients with diabetes, because of the risk of renal impairment. There is also a warning to avoid the use of aliskiren with ACEIs or ARBs in patients with a glomerular filtration rate <60 mL/min. Conversely, methyldopa usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Normal or elevated plasma renin activity may decrease during methyldopa therapy. Hydrochlorothiazide may be a useful addition in stage III CKD but is unlikely to be effective in patients with a glomerular filtration rate <30 mL/min. Amlodipine is also a reasonable add-on medication to consider in this scenario.
A 57-year-old woman with multidrug-resistant hypertension presents to her primary care doctor with multiple complaints. Her antihypertensive regimen consists of valsartan, hydralazine, amlodipine, captopril, and hydrochlorothiazide.
Which of the following pairings of medication and side effect are most likely to be correct?
Hydralazine and ankle edema. Vasodilatory lower extremity edema is most commonly seen with direct arteriolar dilators such as hydralazine and minoxidil. Dihydropyridine calcium antagonists, such as amlodipine, and αadrenergic antagonists, such as doxazosin, are also associated with extremity edema. ACEIs are associated with an approximate 20% incidence of cough, which is purported to be bradykinin mediated. Angiotensin receptor antagonists, such as valsartan, do not directly inhibit angiotensin-converting enzyme activity or inhibit the breakdown of bradykinin. However, there are reports of angiotensin receptor antagonist-associated cough, but the incidence, severity, and frequency of dry cough in patients receiving valsartan or losartan are equivalent to those receiving placebo. Sleep disturbance is a side effect of β-blockers, especially those that cross the blood-brain barrier (e.g., propranolol and metoprolol). Constipation is a frequent side effect of verapamil.
A 19-year-old young man presents with an aortic root diameter of 4.4 cm and a strong family history of aortic dissection. His father died of a type A dissection at age 42, and his older brother recently underwent aortic root repair for an aneurysm measuring 5.6 cm in diameter. Both brothers have the fibrillin-1 gene mutation. The patient currently receives metoprolol 50 mg daily, with a pulse of 55 bpm and blood pressure measurements in the range of 115 to 125/65 to 75 mmHg.
Which additional medication should be added?
Losartan. Both brothers carry the gene mutation for Marfan syndrome; presumably their father’s fatal aortic dissection was also a result of this connective tissue disease. Recent data suggest that the ARB losartan may slow the progression of aortic root dilatation in Marfan syndrome. Initially promising animal model studies demonstrating the benefits of transforming growth factor-beta pathway blockade by losartan have now translated into human clinical trials demonstrating benefit for patients with Marfan syndrome. In a randomized controlled trial of 233 Marfan patients, aortic root dilatation rate per MRI was significantly lower in the losartan group, when compared with controls, at a mean of 3-year follow-up.
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