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November 02, 2021; 97 (18) Research Article

Biomarkers for Atrial Fibrillation Detection After Stroke

Systematic Review and Meta-analysis

Alan Cameron, Huen Ki Cheng, Ren-Ping Lee, Daniel Doherty, Mark Hall, View ORCID ProfilePouria Khashayar, View ORCID ProfileGregory Y. H. Lip, Terence Quinn, Azmil Abdul-Rahim, Jesse Dawson
First published September 9, 2021, DOI: https://doi.org/10.1212/WNL.0000000000012769
Alan Cameron
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Huen Ki Cheng
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Ren-Ping Lee
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Daniel Doherty
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Mark Hall
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Pouria Khashayar
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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  • ORCID record for Pouria Khashayar
Gregory Y. H. Lip
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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  • ORCID record for Gregory Y. H. Lip
Terence Quinn
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Azmil Abdul-Rahim
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Jesse Dawson
From the Institute of Cardiovascular and Medical Sciences (A.C., H.K.C., R.-P.L., D.D., M.H., P.K., T.Q., J.D.) and Institute of Neuroscience and Psychology (A.A.-R.), University of Glasgow, UK; Faculty of Medicine (H.K.C.), University of Hong Kong, Pokfulam; and Liverpool Centre for Cardiovascular Science (G.L.), University of Liverpool, UK.
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Biomarkers for Atrial Fibrillation Detection After Stroke
Systematic Review and Meta-analysis
Alan Cameron, Huen Ki Cheng, Ren-Ping Lee, Daniel Doherty, Mark Hall, Pouria Khashayar, Gregory Y. H. Lip, Terence Quinn, Azmil Abdul-Rahim, Jesse Dawson
Neurology Nov 2021, 97 (18) e1775-e1789; DOI: 10.1212/WNL.0000000000012769

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Abstract

Background and Objective To identify clinical, ECG, and blood-based biomarkers associated with atrial fibrillation (AF) detection after ischaemic stroke or TIA that could help inform patient selection for cardiac monitoring.

Methods We performed a systematic review and meta-analysis and searched electronic databases for cohort studies from January 15, 2000, to January 15, 2020. The outcome was AF ≥30 seconds within 1 year after ischemic stroke/TIA. We used random effects models to create summary estimates of risk. Risk of bias was assessed using the Quality in Prognostic Studies tool.

Results We identified 8,503 studies, selected 34 studies, and assessed 69 variables (42 clinical, 20 ECG, and 7 blood-based biomarkers). The studies included 11,569 participants and AF was detected in 1,478 (12.8%). Overall, risk of bias was moderate. Variables associated with increased likelihood of AF detection are older age (odds ratio [OR] 3.26, 95% confidence interval [CI] 2.35–4.54), female sex (OR 1.47, 95% CI 1.23–1.77), a history of heart failure (OR 2.56, 95% CI 1.87–3.49), hypertension (OR 1.42, 95% CI 1.15–1.75) or ischemic heart disease (OR 1.80, 95% CI 1.34–2.42), higher modified Rankin Scale (OR 6.13, 95% CI 2.93–12.84) or National Institutes of Health Stroke Scale score (OR 2.50, 95% CI 1.64–3.81), no significant carotid/intracranial artery stenosis (OR 3.23, 95% CI 1.14–9.11), no tobacco use (OR 1.93, 95% CI 1.48–2.51), statin therapy (OR 2.07, 95% CI 1.14–3.73), stroke as index diagnosis (OR 1.59, 95% CI 1.17–2.18), systolic blood pressure (OR 1.61, 95% CI 1.16–2.22), IV thrombolysis treatment (OR 2.40, 95% CI 1.83–3.16), atrioventricular block (OR 2.12, 95% CI 1.08–4.17), left ventricular hypertrophy (OR 2.21, 95% CI 1.03–4.74), premature atrial contraction (OR 3.90, 95% CI 1.74–8.74), maximum P-wave duration (OR 3.19, 95% CI 1.40–7.25), PR interval (OR 2.32, 95% CI 1.11–4.83), P-wave dispersion (OR 7.79, 95% CI 4.16–14.61), P-wave index (OR 3.44, 95% CI 1.87–6.32), QTc interval (OR 3.68, 95% CI 1.63–8.28), brain natriuretic peptide (OR 13.73, 95% CI 3.31–57.07), and high-density lipoprotein cholesterol (OR 1.49, 95% CI 1.17–1.88) concentrations. Variables associated with reduced likelihood are minimum P-wave duration (OR 0.53, 95% CI 0.29–0.98), low-density lipoprotein cholesterol (OR 0.73, 95% CI 0.57–0.93), and triglyceride (OR 0.51, 95% CI 0.41–0.64) concentrations.

Discussion We identified multimodal biomarkers that could help guide patient selection for cardiac monitoring after ischaemic stroke/TIA. Their prognostic utility should be prospectively assessed with AF detection and recurrent stroke as outcomes.

Glossary

AF=
atrial fibrillation;
ANP=
atrial natriuretic peptide;
BNP=
brain natriuretic peptide;
CI=
confidence interval;
IHD=
ischemic heart disease;
IVT=
IV thrombolysis;
LDL=
low-density lipoprotein;
LVH=
left ventricular hypertrophy;
MRproANP=
midregional pro-atrial natriuretic peptide;
mRS=
modified Rankin Scale;
NIHSS=
National Institutes of Health Stroke Scale;
NT-proBNP=
N-terminal pro-brain natriuretic peptide;
OR=
odds ratio;
PAC=
premature atrial contraction;
PWD=
P-wave dispersion;
SBP=
systolic blood pressure

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally and are co–first authors.

  • ↵† These authors contributed equally and are co–last authors.

  • CME Course: NPub.org/cmelist

  • Received March 3, 2021.
  • Accepted in final form August 18, 2021.
  • © 2021 American Academy of Neurology
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Letters: Rapid online correspondence

  • Reader Response: Biomarkers for Atrial Fibrillation Detection After Stroke
    • Maurizio Acampa, MD, PhD, Internal medicine physician, Stroke Unit, University of Siena, Italy
    • Pietro Enea Lazzerini, MD, professor, Internal medicine physician, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy
    • Giuseppe Martini, MD, professor, Cardiologist, Stroke Unit, University of Siena, Italy
    Submitted September 28, 2021
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