• Iziah E Sama, Alice Ravera, Bernadet T Santema, Harry van Goor, Jozine M Ter Maaten, Cleland John G F JGF Robertson Centre for Biostatistics & Clinical Trials Unit, University of Glasgow and National Heart & Lung Institute, Imperial College, London, UK., Michiel Rienstra, Alex W Friedrich, Nilesh J Samani, Leong L Ng, Kenneth Dickstein, Chim C Lang, Gerasimos Filippatos, Stefan D Anker, Piotr Ponikowski, Marco Metra, Dirk J van Veldhuisen, and Adriaan A Voors.
• Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
• Eur. Heart J. 2020 May 14; 41 (19): 1810-1817.

AimsThe 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 ResultsWe 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.ConclusionIn 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.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.

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