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

Zimmermann, Tobias; Walter, Joan Elias; Lopez‐Ayala, Pedro; Strebel, Ivo; Amrein, Melissa; Koechlin, Michael; Honegger, Ursina; Mueller, Christian; Albus, Miriam; Zellweger, Michael; Liu, Yu‐Ching; Glarner, Noemi; Boeddinghaus, Jasper; Freese, Michael; Haaf, Philip; Gualandro, Danielle M.; Prepoudis, Alexandra; Leu, Kathrin; Schaerli, Nicolas; Belkin, Maria; Wildi, Karin; Puelacher, Christian; Shrestha, Samyut; Wussler, Desiree; Diebold, Matthias; Rentsch, Katharina; Buser, Andreas; du Fay de Lavallaz, Jeanne; Koechlin, Luca; Twerenbold, Raphael; Nestelberger, Thomas

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.