Evidence map›Paper›PMID 32388565›Full record

ArticleEuropean heart journal2020

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

Iziah E Sama, Alice Ravera, Bernadet T Santema, Harry van Goor, Jozine M Ter Maaten, John G F Cleland, Michiel Rienstra, Alex W Friedrich, Nilesh J Samani, Leong L Ng and 8 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European heart journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 267 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
267citing papers in PubMed, 4 pooled it
11.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

267 citing papers in PubMed, 4 syntheses or guidelines pooled it, 487 citations in OpenAlex.

  1. Pooled it
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  9. Renin-angiotensin-aldosterone system inhibitors - why they won't help in COVID-19.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
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  16. ADAM-17 Activity and Its Relation to ACE2: Implications for Severe COVID-19.International journal of molecular sciences · 2024
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207 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 9 institutions in 8 countries.

Iziah E SamaDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Alice RaveraDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Bernadet T SantemaDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Harry van GoorDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Jozine M Ter MaatenDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
John G F ClelandRobertson Centre for Biostatistics & Clinical Trials Unit, University of Glasgow and National Heart & Lung Institute, Imperial College, London, UK.
Michiel RienstraDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Alex W FriedrichDepartment of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Biomedical Research Centre, Leicester, UK.
Leong L NgDepartment of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Biomedical Research Centre, Leicester, UK.
Kenneth DicksteinUniversity of Bergen, Bergen, Norway.
Chim C LangDivision of Molecular and Clinical Medicine, School of Medicine, University of Dundee Ninewells Hospital and Medical School, Dundee, UK.
Gerasimos FilippatosNational and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Stefan D AnkerDepartment of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT), Germany.
Piotr PonikowskiDepartment of Heart Diseases, Medical University, Military Hospital, Wrocław, Poland.
Marco MetraCardiology, Department of Medical and Surgical Specialties, Radiologic Sciences and Public Health, University of Brescia, Brescia, Italy.
Dirk J van VeldhuisenDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Adriaan A VoorsDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
University Medical Center Groningen · NLUniversity of Leicester · GBGerman Centre for Cardiovascular Research · DEImperial College London · GBNational and Kapodistrian University of Athens · GRStavanger University Hospital · NOUniversity of Brescia · ITUniversity of Dundee · GBWroclaw Medical University · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

AgedAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBetacoronavirusCoronavirus InfectionsCOVID-19EuropeFemaleHeart FailureHumansMaleMiddle AgedMineralocorticoid Receptor AntagonistsPandemicsPeptidyl-Dipeptidase AACE2 protein, humanAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsMineralocorticoid Receptor AntagonistsPeptidyl-Dipeptidase AACE2Coronavirus disease (COVID-19)Heart failureMen

Identifiers

PMID32388565
PMCPMC7239195
OpenAlexW3022149127

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.