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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?

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Abstract

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.

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Authors and Affiliations

  1. Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Room EE1418b, Erasmus MC, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands

    Joyce E.M. Schilders, Haiyan Wu, Frans Boomsma, Anton H. van den Meiracker & A.H. Jan Danser

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  1. Joyce E.M. Schilders
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  2. Haiyan Wu
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Correspondence to A.H. Jan Danser.

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Schilders, J.E., Wu, H., Boomsma, F. et al. 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?. Cardiovasc Drugs Ther 28, 335–345 (2014). https://doi.org/10.1007/s10557-014-6537-6

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