Examination of Baseline Levels of Carboxypeptidase N and Complement Components as Potential Predictors of Angioedema Associated With the Use of an Angiotensin-Converting Enzyme Inhibitor

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To determine if mean levels of complement components and carboxypeptidase N differed when comparing patients who exhibited angioedema following angiotensin-converting enzyme inhibitor therapy to those who received angiotensin-converting enzyme inhibitor therapy but did not have angioedema. Case-control study nested within an 8-week, open-label study of the use of quinapril hydrochloride for hypertension in 12275 patients. Multicenter, with sites throughout the United States. Of the 36 patients with angioedema described, 22 participated in the study. They were matched to 48 controls by age, sex, race, length of follow-up, and geographical region. All patients received quinapril therapy prior to participation in this case-control study. Levels of carboxypeptidase N, total hemolytic complement, C1 esterase inhibitor, and C4, along with questionnaire data, including a history of angioedema-like episodes and family history of angioedema. The 22 patients had significantly lower mean levels of carboxypeptidase N (kininase I) (P = .03) and C1 esterase inhibitor (P = .04) compared with the 48 matched controls, but all mean values were within normal laboratory ranges. A history of prior angioedema-like episodes was associated with an approximate 6-fold increase in the subsequent risk of angioedema following angiotensin-converting enzyme inhibitor therapy. Small differences in levels of carboxypeptidase N or C1 esterase inhibitor may contribute to an increased risk of angioedema with angiotensin-converting enzyme inhibitor therapy. Given the large overlap in the distributions of carboxypeptidase N and C1 esterase inhibitor levels, prior testing could not be used to evaluate angioedema risk for an individual patient considering angiotensin-converting enzyme inhibitor therapy. A history of prior angioedema-like episodes was associated with increased risk, but this result should be interpreted with caution because of possible recall bias.