Renin-Angiotensin System Phenotyping as a Guidance Toward Personalized Medicine for ACE Inhibitors: can the Response to ACE Inhibition be Predicted on the Basis of Plasma Renin or ACE?

• Published in: Cardiovascular drugs and therapy Vol. 28; no. 4; pp. 335 - 345
• Main Authors: Schilders, Joyce E.M., Wu, Haiyan, Boomsma, Frans, van den Meiracker, Anton H., Danser, A.H. Jan
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2014; Springer; Springer Nature B.V
• Subjects: Aged; Aldosterone - blood; Angiotensin I - blood; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Benzimidazoles - pharmacology; Benzimidazoles - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; Cardiology; Cardiovascular system; Cross-Over Studies; Diuretics - pharmacology; Diuretics - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Enalapril - pharmacology; Enalapril - therapeutic use; Female; Humans; Hydrochlorothiazide - pharmacology; Hydrochlorothiazide - therapeutic use; Hypertension - blood; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Original Article; Peptidyl-Dipeptidase A - blood; Pharmacology. Drug treatments; Phenotype; Precision Medicine; Renin - blood; Renin-Angiotensin System; Tetrazoles - pharmacology; Tetrazoles - therapeutic use; Renin; ACE; Enalapril; Candesartan; Phenotyping; Therapeutic efficacy; Hydrochlorothiazide; Imidazole derivatives; Benzothiadiazine derivatives; Biological fluid; Tetrazole derivatives; Peptide hormone; Blood plasma; Diuretic; Octapeptide; Peptidyl-dipeptidase A; Efficiency; Aspartic endopeptidases; Angiotensin II; Enzyme; Enzyme inhibitor; Guidance; Peptidases; Renin angiotensin system; Treatment; Biphenyl derivatives; Sulfonamides; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; Sartan derivatives; Angiotensin antagonist; Thiazide; ACE inhibitor
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-014-6537-6

Purpose & Methods Not all hypertensive patients respond well to ACE inhibition. Here we determined whether renin-angiotensin system (RAS) phenotyping, i.e., the measurement of renin or ACE, can predict the individual response to RAS blockade, either chronically (enalapril vs. enalapril + candesartan) or acutely (enalapril ± hydrochlorothiazide, HCT). Results Chronic enalapril + candesartan induced larger renin rises, but did not lower blood pressure (BP) more than enalapril. Similar observations were made for enalapril + HCT vs. enalapril when given acutely. Baseline renin predicted the peak changes in BP chronically, but not acutely. Baseline ACE levels had no predictive value. Yet, after acute drug intake, the degree of ACE inhibition, like Δrenin, did correlate with ΔBP. Only the relationship with Δrenin remained significant after chronic RAS blockade. Thus, a high degree of ACE inhibition and a steep renin rise associate with larger acute responses to enalapril. However, variation was large, ranging >50 mm Hg for a given degree of ACE inhibition or Δrenin. The same was true for the relationships between Δrenin and ΔBP, and between baseline renin and the maximum reduction in BP in the chronic study. Conclusions Our data do not support that RAS phenotyping will help to predict the individual BP response to RAS blockade. Notably, these conclusions were reached in a carefully characterized, homogenous population, and when taking into account the known fluctuations in renin that relate to gender, age, ethnicity, salt intake and diuretic treatment, it seems unlikely that a cut-off renin level can be defined that has predictive value.