Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;8(2):1717-1721.
doi: 10.1002/ehf2.13249. Epub 2021 Feb 19.

Influence of renin-angiotensin-aldosterone system inhibitors on plasma levels of angiotensin-converting enzyme 2

Tobias Zimmermann  1   2 , Joan Elias Walter  1   3 , Pedro Lopez-Ayala  1 , Ivo Strebel  1 , Melissa Amrein  1 , Michael Koechlin  1 , Ursina Honegger  1 , Christian Mueller  1 ; BASEL VIII Investigators
Collaborators, Affiliations

Influence of renin-angiotensin-aldosterone system inhibitors on plasma levels of angiotensin-converting enzyme 2

Tobias Zimmermann et al. ESC Heart Fail. 2021 Apr.

Abstract

Aims: Concern has been raised that treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the expression of angiotensin-converting enzyme 2 (ACE2), which acts as the entry receptor for SARS-CoV-2, and lead to an increased risk of death from SARS-CoV-2. We aimed to address this concern by evaluating the in vivo relationship of treatment with ACE inhibitors and angiotensin receptor blockers (ARB) with circulating plasma concentrations of ACE2 in a large cohort of patients with established cardiovascular disease (n = 1864) or cardiovascular risk factors (n = 2144) but without a history of heart failure.

Methods and results: Angiotensin-converting enzyme 2 was measured in 4008 patients (median age 68, 33% women, 31% on ACE-inhibitors, 31% on ARB) using the SOMAscan proteomic platform (SomaLogic Inc, Colorado, USA). Plasma concentration of ACE2 was comparable in 1250 patients on ACE inhibitors (mean 5.99) versus patients without ACE inhibitors (mean 5.98, P = 0.54). Similarly, plasma concentration of ACE2 was comparable in 1260 patients on ARB (mean 5.99) versus patients without ARB (mean 5.98, P = 0.50). Plasma concentration of ACE2 was comparable in 2474 patients on either ACE inhibitors or ARB (mean 5.99) versus patients without ACE inhibitors or ARB (mean 5.98, P = 0.31). Multivariable quantile regression model analysis confirmed the lack of association between treatment with ACE inhibitors or ARB and ACE2 concentrations. Body mass index showed the only positive association with ACE2 plasma concentration (effect 0.015, 95% confidence interval 0.002 to 0.028, P = 0.024).

Conclusions: In a large cohort of patients with established cardiovascular disease or cardiovascular risk factors but without heart failure, ACE inhibitors and ARB were not associated with higher plasma concentrations of ACE2.

Keywords: ACE; ACE2; ARB; Covid‐19; Plasma levels; RAAS; SARS‐CoV‐2.

PubMed Disclaimer

Conflict of interest statement

Dr. Zimmermann reports research grants from the Freiwillige Akademische Gesellschaft Basel. Dr. Walter reports research grants from the Swiss Heart Foundation (FF19097 and F18111) and the Swiss Academy of Medical Sciences and Bangerter Foundation. Dr. Mueller has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Astra Zeneca, Beckman Coulter, Biomerieux, BRAHMS, Critical Diagnostics, Roche, Siemens, Singulex, and Sphingotec, as well as speaker/consulting honoraria from Abbott, Alere, Astra Zeneca, Bayer, Biomerieux, Boehringer Ingelheim, BMS, BRAHMS, Cardiorentis, Novartis, Roche, Sanofi, Siemens, and Singulex. All other authors declare that they have no conflict of interest with this study. All authors critically reviewed the manuscript and approved the final version for submission. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation or approval of the manuscript.

Figures

Figure 1
Figure 1
ACE2 concentrations in patients stratified by use of ACEi and/or ARB. ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; ACE2, angiotensin‐converting enzyme 2; NS, non‐significant.
See this image and copyright information in PMC

References

    1. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin–angiotensin–aldosterone system blockers and the risk of Covid‐19. N Engl J Med 2020; 382: 2431–2440. - PMC - PubMed
    1. Hoffmann M, Kleine‐Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N‐H, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS‐CoV‐2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 271–280.e8. - PMC - PubMed
    1. Walter J, du Fay de Lavallaz J, Koechlin L, Zimmermann T, Boeddinghaus J, Honegger U, Strebel I, Twerenbold R, Amrein M, Nestelberger T, Wussler D, Puelacher C, Badertscher P, Zellweger M, Fahrni G, Jeger R, Kaiser C, Reichlin T, Mueller C. Using high‐sensitivity cardiac troponin for the exclusion of inducible myocardial ischemia in symptomatic patients. Ann Intern Med 2020; 172: 175–185. - PubMed
    1. Ganz P, Heidecker B, Hveem K, Jonasson C, Kato S, Segal MR, Sterling DG, Williams SA. Development and validation of a protein‐based risk score for cardiovascular outcomes among patients with stable coronary heart disease. JAMA ‐ J Am Med Assoc 2016; 315: 2532–2541. - PubMed
    1. Sama IE, Ravera A, Santema BT, van Goor H, ter Maaten JM, Cleland JGF, Rienstra M, Friedrich AW, Samani NJ, Ng LL, Dickstein K, Lang CC, Filippatos G, Anker SD, Ponikowski P, Metra M, van Veldhuisen DJ, Voors AA. Circulating plasma concentrations of angiotensin‐converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors. Eur Heart J 2020; 41: 1810–1817. - PMC - PubMed

Publication types

Substances