EXAMINATION OF BASE-LINE LEVELS OF CARBOXYPEPTIDASE-N AND COMPLEMENT COMPONENTS AS POTENTIAL PREDICTORS OF ANGIOEDEMA ASSOCIATED WITH THE USE OF AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

Objective: To determine if mean levels of complement components and ca rboxypeptidase N differed when comparing patients who exhibited angioe dema following angiotensin-converting enzyme inhibitor therapy to thos e who received angiotensin-converting enzyme inhibitor therapy but did not have angioedema. Design: Case-control study nested within an 8-we ek, open-label study of the use of quinapril hydrochloride for hyperte nsion in 12 275 patients. Setting: Multicenter, with sites throughout the United States, Patients: Of the 36 patients with angioedema descri bed, 22 participated in the study. They were matched to 48 controls by age, sex: race, length of follow-up, and geographical region. Interve ntion: All patients received quinapril therapy; prior to participation in this case-control study. Main Outcome Measures: Levels of carboxyp eptidase 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. Results: The 22 patients h ad 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 appr oximate 6-fold increase in the subsequent risk of angioedema following angiotensin-converting enzyme inhibitor therapy. Conclusions: Small d ifferences in levels of carboxypeptidase N or C1 esterase inhibitor ma y contribute to an increased risk of angioedema with angiotensin-conve rting enzyme inhibitor therapy, Given the large overlap in the distrib utions of carboxypeptidase N and C1 esterase inhibitor levels, prior t esting 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 increa sed risk, but this result should be interpreted with caution because o f possible recall bias.