A 43-year-old woman comes to the physician with lower-extremity edema over the last week. She has no cough, shortness of breath, chest pain, or leg pain. Medical history is significant for diet-controlled type 2 diabetes mellitus and hypertension. Her antihypertensive regimen was recently adjusted. Blood pressure is 133/80 mm Hg and BMI is 27 kg/m². Physical examination shows bilateral pedal edema but is otherwise unremarkable. Which of the following is most likely responsible for this patient's symptoms?

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Peripheral edema is a common side effect of calcium channel blocker (CCB) therapy, with a reported incidence of approximately 25% after 6 months of therapy. The edema is likely related to preferential dilation of precapillary vessels (arteriolar dilation), which leads to increased capillary hydrostatic pressure and fluid extravasation into the interstitium. Dihydropyridine (DHP) CCBs such as amlodipine and nifedipine are potent arteriolar dilators and cause more peripheral edema than non-dihydropyridine CCBs (eg, diltiazem, verapamil). Other major side effects associated with DHP CCBs include headache, flushing, and dizziness. Renin-angiotensin system antagonists (angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) cause post-capillary venodilation and can normalize the increased capillary hydrostatic pressure. In clinical studies, the combination of CCB and ACE inhibitors was associated with a significantly lower risk of CCB-associated peripheral edema compared with CCB monotherapy. (Choice B) The most common side effects of hydrochlorothiazide are electrolyte imbalances (eg, hyponatremia, hypokalemia), renal failure, hyperuricemia (which may precipitate acute gout), and elevated glucose and cholesterol levels. However, hydrochlorothiazide does not cause peripheral edema. (Choices C and E) ACE inhibitors can cause angioedema in approximately 0.1%-0.7% of patients. Patients typically present with nonpitting swelling of the subcutaneous or submucosal tissue, most commonly the lips, tongue, face, and upper airway. ACE inhibitors do not cause peripheral or dependent edema. The risk of angioedema is much lower with ARBs (eg, losartan). (Choice D) Side effects associated with beta blocker use include worsening of congestive heart failure, bradyarrhythmias, increased airway resistance in patients with asthma, generalized fatigue, and sexual dysfunction. Beta blockers are not associated with peripheral edema. Educational objective: Peripheral edema is a common side effect of dihydropyridine calcium channel blockers (CCBs). Addition of a renin-angiotensin system antagonist (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker) can reduce CCB-associated peripheral edema. References: Peripheral edema associated with calcium channel blockers: incidence and withdrawal rate - a meta-analysis of randomized trials. (http://www.ncbi.nlm.nih.gov/pubmed/21558959) Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. (http://www.ncbi.nlm.nih.gov/pubmed/21295192)

A 43-Year-Old Woman Comes to the Physician with Lower-Extremity Edema