Evidence map›Paper›PMID 33010842›Full record

ArticleLancet (London, England)2020

Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis.

Sukrit Narula, Salim Yusuf, Michael Chong, Chinthanie Ramasundarahettige, Sumathy Rangarajan, Shrikant I Bangdiwala, Martin van Eikels, Kirsten Leineweber, Annie Wu, Marie Pigeyre and 1 more

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

Article in Lancet (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 3 pooled it
18.6field-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

107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 167 citations in OpenAlex.

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  12. Genetic Analysis and Clinical Effect ofSultan Qaboos University medical journal · 2026
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  14. Circulating Cardiovascular Proteomic Associations With Genetics and Disease.Circulation. Genomic and precision medicine · 2025
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  16. The renin-angiotensin system in models of pulmonary arterial hypertension vs primary hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
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47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Sukrit NarulaPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Salim YusufPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
Michael ChongPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
Chinthanie RamasundarahettigePopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
Sumathy RangarajanPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
Shrikant I BangdiwalaPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Martin van EikelsBayer, Leverkusen, Nordrhein-Westfalen, Germany.
Kirsten LeineweberBayer, Leverkusen, Nordrhein-Westfalen, Germany.
Annie WuPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
Marie PigeyrePopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Medicine, Michael G DeGroote School of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
Guillaume ParéPopulation Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada. Electronic address: pareg@mcmcaster.ca.
Hamilton Health Sciences · CAMcMaster University · CABayer (Germany) · DEImpact · CAPopulation Health Research Institute · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAngiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events.

methodsWe used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America). We measured plasma concentrations of ACE2 and assessed potential determinants of plasma ACE2 levels as well as the association of ACE2 with cardiovascular events.

findingsWe included 10 753 PURE participants in our study. Increased concentration of plasma ACE2 was associated with increased risk of total deaths (hazard ratio [HR] 1·35 per 1 SD increase [95% CI 1·29-1·43]) with similar increases in cardiovascular and non-cardiovascular deaths. Plasma ACE2 concentration was also associated with higher risk of incident heart failure (HR 1·27 per 1 SD increase [1·10-1·46]), myocardial infarction (HR 1·23 per 1 SD increase [1·13-1·33]), stroke (HR 1·21 per 1 SD increase [1·10-1·32]) and diabetes (HR 1·44 per 1 SD increase [1·36-1·52]). These findings were independent of age, sex, ancestry, and traditional cardiac risk factors. With the exception of incident heart failure events, the independent relationship of ACE2 with the clinical endpoints, including death, remained robust after adjustment for BNP. The highest-ranked determinants of ACE2 concentrations were sex, geographic ancestry, and body-mass index (BMI). When compared with clinical risk factors (smoking, diabetes, blood pressure, lipids, and BMI), ACE2 was the highest ranked predictor of death, and superseded several risk factors as a predictor of heart failure, stroke, and myocardial infarction.

interpretationIncreased plasma ACE2 concentration was associated with increased risk of major cardiovascular events in a global study.

fundingCanadian Institute of Health Research, Heart & Stroke Foundation of Canada, and Bayer.

Indexed as

AdultAgedAngiotensin-Converting Enzyme 2Body Mass IndexCardiovascular DiseasesCase-Control StudiesFemaleHumansMaleMiddle AgedPeptidyl-Dipeptidase ARisk FactorsSurvival RateACE2 protein, humanAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase A

Identifiers

PMID33010842
PMCPMC7529405
OpenAlexW3090997876

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.