Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors
- PMID: 32388565
- PMCID: PMC7239195
- DOI: 10.1093/eurheartj/ehaa373
Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors
Abstract
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.
Keywords: ACE2; Coronavirus disease (COVID-19); Heart failure; Men.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
Figures
Comment in
-
Plasma angiotensin-converting enzyme 2: novel biomarker in heart failure with implications for COVID-19.Eur Heart J. 2020 May 14;41(19):1818-1820. doi: 10.1093/eurheartj/ehaa414. Eur Heart J. 2020. PMID: 32388547 Free PMC article. No abstract available.
-
ACE2 is on the X chromosome: could this explain COVID-19 gender differences?Eur Heart J. 2020 Jun 1;41(32):3095. doi: 10.1093/eurheartj/ehaa521. Eur Heart J. 2020. PMID: 32577716 Free PMC article. No abstract available.
-
Circulating plasma angiotensin-converting enzyme 2 concentrations in patients with kidney disease.Eur Heart J. 2020 Jul 1;41(32):3097-3098. doi: 10.1093/eurheartj/ehaa523. Eur Heart J. 2020. PMID: 32691065 Free PMC article. No abstract available.
-
COVID-19: (mis)managing an announced Black Swan.Eur Heart J. 2020 May 14;41(19):1779-1782. doi: 10.1093/eurheartj/ehaa435. Eur Heart J. 2020. PMID: 33216860 Free PMC article. No abstract available.
Similar articles
-
Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS).Med Hypotheses. 2020 Oct;143:110112. doi: 10.1016/j.mehy.2020.110112. Epub 2020 Jul 16. Med Hypotheses. 2020. PMID: 32721806 Free PMC article.
-
Cardiovascular Pharmacology in the Time of COVID-19: A Focus on Angiotensin-Converting Enzyme 2.J Cardiovasc Pharmacol. 2020 Jun;75(6):526-529. doi: 10.1097/FJC.0000000000000840. J Cardiovasc Pharmacol. 2020. PMID: 32301766 Free PMC article. Review.
-
Influence of renin-angiotensin-aldosterone system inhibitors on plasma levels of angiotensin-converting enzyme 2.ESC Heart Fail. 2021 Apr;8(2):1717-1721. doi: 10.1002/ehf2.13249. Epub 2021 Feb 19. ESC Heart Fail. 2021. PMID: 34596976 Free PMC article.
-
Clinical Implications of SARS-CoV-2 Interaction With Renin Angiotensin System: JACC Review Topic of the Week.J Am Coll Cardiol. 2020 Jun 23;75(24):3085-3095. doi: 10.1016/j.jacc.2020.04.028. Epub 2020 Apr 16. J Am Coll Cardiol. 2020. PMID: 32305401 Free PMC article. Review.
-
Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study.Hypertension. 2020 Jul;76(1):51-58. doi: 10.1161/HYPERTENSIONAHA.120.15143. Epub 2020 Apr 29. Hypertension. 2020. PMID: 32348166
Cited by
-
Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3).BMJ Open Diabetes Res Care. 2024 May 30;12(3):e004237. doi: 10.1136/bmjdrc-2024-004237. BMJ Open Diabetes Res Care. 2024. PMID: 38816205 Free PMC article.
-
Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus.World J Diabetes. 2024 Apr 15;15(4):606-622. doi: 10.4239/wjd.v15.i4.606. World J Diabetes. 2024. PMID: 38680697 Free PMC article. Review.
-
A GMR enzymatic assay for quantifying nuclease and peptidase activity.Front Bioeng Biotechnol. 2024 Mar 13;12:1363186. doi: 10.3389/fbioe.2024.1363186. eCollection 2024. Front Bioeng Biotechnol. 2024. PMID: 38544982 Free PMC article.
-
Burden and risk profile of acute kidney injury in severe COVID-19 pneumonia admissions: a Finding from Jimma University medical center, Ethiopia.BMC Nephrol. 2024 Mar 20;25(1):109. doi: 10.1186/s12882-024-03522-0. BMC Nephrol. 2024. PMID: 38504176 Free PMC article.
-
Predictors of SARS-CoV-2 Infection and Severe and Lethal COVID-19 after Three Years of Follow-Up: A Population-Wide Study.Viruses. 2023 Aug 24;15(9):1794. doi: 10.3390/v15091794. Viruses. 2023. PMID: 37766201 Free PMC article.
References
-
- Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020;doi: 10.1016/S2213-2600(20)30079-5. - PMC - PubMed
-
- Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY,, Xiang J,, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J,, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;doi: 10.1056/NEJMoa2002032. - PMC - PubMed
-
- Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020;doi: 10.1001/jama.2020.4683. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous