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Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors

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posted on 01.07.2020, 10:19 by IE Sama, A Ravera, BT Santema, H Van Goor, JM Ter Maaten, JGF Cleland, M Rienstra, AW Friedrich, NJ Samani, LL Ng, K Dickstein, CC Lang, G Filippatos, SD Anker, P Ponikowski, M Metra, DJ Van Veldhuisen, AA Voors
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com. AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.

History

Citation

European Heart Journal, Volume 41, Issue 19, 14 May 2020, Pages 1810–1817, https://doi.org/10.1093/eurheartj/ehaa373

Author affiliation

Department of Cardiovascular Science

Version

AM (Accepted Manuscript)

Published in

European Heart Journal

Volume

41

Issue

19

Pagination

1810 - 1817

Publisher

Oxford University Press (OUP)

issn

0195-668X

eissn

1522-9645

Acceptance date

20/04/2020

Copyright date

2020

Available date

10/05/2021

Spatial coverage

England

Language

English

Publisher version

https://academic.oup.com/eurheartj/article/41/19/1810/5834647