TY - JOUR
T1 - Circulating plasma concentrations of ACE2 in men and women with heart failure and effects of renin-angiotensin-aldosterone-inhibitors
AU - Sama, Iziah E.
AU - Ravera, Alice
AU - Santema, Bernadet T.
AU - van Goor, Harry
AU - ter Maaten, Jozine M.
AU - Cleland, John G. F.
AU - Rienstra, Michiel
AU - Friedrich, Alexander W.
AU - Samani, Nilesh J.
AU - Ng, Leong Loke
AU - Dickstein, Kenneth
AU - Lang, Chim C.
AU - Filippatos, Gerasimos
AU - Anker, Stefan D.
AU - Ponikowski, Piotr
AU - Metra, Marco
AU - van Veldhuisen, Dirk Jan
AU - Voors, Adriaan A.
N1 - Funding Information:
This work was supported by a grant from the European Commission (FP7-242209-BIOSTAT-CHF).
Funding Information:
Conflict of interest: B.T.S reports grants from the Dutch Heart Foundation (2019T094), during the conduct of this study. J.G.F.C. reports grants and personal fees from Amgen, Novartis, Pharmacosmos, and Vifor, and personal fees from Servier, outside the submitted work. S.D.A. reports personal fees from Bayer, Boehringer Ingelheim, Cardiac Dimension, Impulse Dynamics, Novartis, Servier, St. Jude Medical, and Vifor Pharma, and grant support from Abbott Vascular and Vifor Pharma, outside the submitted work. G.F. reports being a Committee Member in trials sponsored by Medtronic, Vifor, Servier, Novartis, and BI, outside the submitted work. M.M. reports personal fees from Consulting honoraria for participation to trials’ committees or advisory boards from Abbott vascular, Amgen, Astra-Zeneca, Bayer and Vifor pharma in the last 3 years, personal fees from Fees for public speeches in sponsored symposia from Abbott vascular and Edwards Therapeutics, outside the submitted work. All other authors have no conflicts to declare.
Publisher Copyright:
© The Author(s) 2020.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/14
Y1 - 2020/5/14
N2 - 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.
AB - 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.
KW - Men
KW - Heart Failure
KW - Coronavirus disease (COVID-19)
KW - ACE2
KW - Heart failure
KW - Coronavirus Infections
KW - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
KW - Pandemics
KW - Europe
KW - Humans
KW - Middle Aged
KW - Male
KW - Mineralocorticoid Receptor Antagonists/therapeutic use
KW - Renin-Angiotensin System/drug effects
KW - Heart Failure/blood
KW - Sex Factors
KW - Betacoronavirus
KW - Female
KW - Peptidyl-Dipeptidase A/blood
KW - Pneumonia, Viral
KW - Aged
KW - Angiotensin Receptor Antagonists/therapeutic use
UR - http://www.scopus.com/inward/record.url?scp=85084617664&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehaa373
DO - 10.1093/eurheartj/ehaa373
M3 - Article
C2 - 32388565
SN - 0195-668X
VL - 41
SP - 1810
EP - 1817
JO - European Heart Journal
JF - European Heart Journal
IS - 19
ER -