ACE Phenotyping as a Guide Toward Personalized Therapy with ACE Inhibitors

Sergei M. Danilov, Stan I. Tovsky, David E. Schwartz, Randal O. Dull

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. Objectives: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype" - for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. Methods: The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Results: Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Conclusion: Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.

Original languageEnglish (US)
Pages (from-to)374-386
Number of pages13
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume22
Issue number4
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Keywords

  • ACE conformation
  • ACE inhibitor
  • ACE phenotyping
  • angiotensin-converting enzyme
  • blood pressure
  • hypertension
  • nonresponders

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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